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The role of radical hysterectomy in adenocarcinoma of the endometrium
GYNECOLOGIC
ONCOLOGY
2,331-347
(1974)
The Role of Radical Hysterectomy in Adenocarcinoma of the Endometrium FELIX The M. D. Anderson
University Hospital
RUTLEDGE, of Texas & Tumor
Received
M.D.
System Cancer Center Institute, Houston, Texas
March
77025
18,1974
A retrospective assessment of treatment results for patients with adenocarcinoma of the endometrium shows little progress for the past 20 yr in management of this disease. These accomplishments may have been affected adversely by the increased number of elderly patients treated within recent years, for the prognosis worsens with advanced age. Likewise, because women are living longer, more enter the age when adenocarcinoma of the endometrium is prevalent, increasing the frequency of this disease. Thus, gynecologic oncologists have become aware that the treatment problem for adenocarcinoma of the endometrium deserves more research for methods to improve survival. The primary lesion is readily curable by hysterectomy. Therefore, it is the metastases which need better therapy. For this purpose, megavoltage irradiation therapy is being used more often to supplement intracavitary radium. However, the role of radical hysterectomy has been reconsidered. A review of the experiences with radical hysterectomy has been summarized from the literature and the conclusions presented.
Compared with cancer at other sites within the body, treatment of cancer of the endometrium is notably successful; yet for some patients, treatment is either misdirected or inadequate because regrowths appear within the pelvie region. A recurring question about the management of carcinoma of the endometrium is why should we not use radical hysterectomy more often. As we consider the question, several additional ones are generated, such as (1) What can be expected technically of the radical hysterectomy which cannot be accomplished by conservative hysterectomy? The obvious answer is wider local resection of the primary lesion and the additional excision of regional nodes. (2) Is metastasis to the upper vagina, parametrium, and the regional nodes sufficiently common to include resection of these tissues routinely? Although we recognize these sites as locations for metastasis from cancer of the endometrium, we need proof that this is a problem in treatment for most of the patients. To resolve the question about the greater role of radical hysterectomy in adenocarcinoma of the endometrium, we must first prove a need to replace conservative hysterectomy with a procedure that resects more widely. We must review the records of those patients who were treated by conservative hysterectomy to decide if failure to cure is often because metastases exist beyond the range of the conservative hysterectomy but within the bounds of the more extended radical hysterectomy. To resolve the question concerning such inadequacies of the conservative hysterectomy, the sites of first appear331 Copyright All rights
@ 1974 by Academic Press, Inc. of reproduction in any form reserved.
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ante of recurrent adenocarcinoma in those patients who are not cured need investigation. A study of the treatment failure sites or locations of the first recurrence should point to the deficiencies of the current standard method of treatment without radical hysterectomy. If recurrences appear commonly within the pelvis after our standard therapy, and if the weaknesses can be corrected by wider resection, then we should consider using radical hysterectomy more often. (3) Do the experiences recorded in the literature prove that radical hysterectomy benefits by this wider excision of the primary and regional nodes? In these reports we should look for the conditions of the disease for which radical hysterectomy improves cure rate. Do patients in both stage I and stage II adenocarcinoma of the endometrium benefit, or only the more advanced stage II and III? To decide the role of radical hysterectomy as a part of an individualized treatment plan, we should also study the reports and outcome of those patients treated by lymphadenectomy without the extended hysterectomy since lymphadenectomy is an important part of the plan for more extended operation. Since cure rates will be the guide to the effectiveness and to the specific accomplishment of excising metastasis, we should note the outcome of those patients who have positive nodes excised. How many patients are cured by excising positive nodes? (4) Can the radical hysterectomy be performed upon patients with adenocarcinoma of the endometrium with safety? Clearly, if we are transferring our opinion of the radical hysterectomy from our experience with its use in patients with carcinoma of the cervix, the poor physical health of patients with carcinoma of the endometrium must be considered more carefully. The patient with adenocarcinoma of the endometrium will be older, obese, often diabetic, and physically infirm with hypertensive cardiovascular disease. (5) If we find evidence that the radical hysterectomy should be used more often, what should be the treatment plan? Advise radical hysterectomy for all patients with adenocarcinoma of the endometrium, thus replacing the conservative hysterectomy as the standard operation, or identify patients individually? If the latter method is needed, then by what criteria do we choose those patients who need the radical hysterectomy? Since the present methods of treatment are so successful, benefits from the more radical operation must be assured by individual selection for the hazards of postoperative complications and deaths are going to be greater. DISCUSSION To return to these questions separately for further consideration: What can we expect of the radical hysterectomy which cannot be accomplished by the conservative hysterectomy? The scope of the radical hysterectomy may excise as much as 50% of the vagina measured by the Iength. This additional removal of the vagina will be therapeutic when adenocarcinoma arising within the corpus spreads down into the cervix and on to the vagina. If such an amount and distribution of carcinoma is to be treated surgically, clearly the extended scope of the radical hysterectomy will be necessary. Many gynecologic oncologists recognize that patients with stage II adenocarcinoma of the
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endometrium are potentially candidates for an operation which removes more of the vagina. A radical hysterectomy also resects parametrium, and this may benefit patients with adenocarcinoma of the corpus involving the lower segment of the uterus, where there is a significant frequency of paracervix metastasis. Within the literature, the statement is repeated that “adenocarcinoma involving the cervix becomes accessible to the lower uterine vasculature and may metastasize laterally by way of the lymphatics serving the cervix. The treatment problem of stage II becomes more like that of cancer of the cervix. Thus, the treatment should be similar” [l-3]. We all recognize that the usefulness of radical hysterectomy for stage I and II carcinoma of the cervix and would be willing to use radical hysterectomy for stage II carcinoma of the endometrium if the spread patterns are indeed similar [4]. Although the use of radical hysterectomy for stage II endometrial carcinoma has good theoretical support, the direction and the schedule for metastasis is still unsettled and may not be sufficiently similar to carcinoma of the cervix for us to assume that an interchange of treatment would be equally effective [5]. Spread may be infrequent, and when present, too complex for surgical excision to make complete excision for all positive nodes feasible. Although the biological behavior of carcinoma of the endometrium favors the patient by a relative reluctance of the cancer to leave the corpus, still lymphatic metastases from the corpus disease stage I do develop [1,6,7]. Extension to the cervix is not necessary for lymphatic metastasis, While the overall incidence of metastasis from stage I adenocarcinoma of the endometrium is approximately 10% and this low incidence may not justify routinely removing the pelvic nodes, some patients may deserve lymphadenectomy. For example, an increased frequency of metastasis to the regional nodes has been demonstrated by some reports [8-111 if there is deep penetration of the uterine wall musculature by the carcinoma, and myometrial invasion occurs earlier when the histologic characteristics of the endometrial cancer are undifferentiated. We must also be reassured that lymphadenectomy will be curative. Since the lymphadenectomy phase of the radical hysterectomy is considered a major aspect of the procedure, we need to understand its potential for increasing the cure rates in those patients treated. Again, we may wish to transfer our knowledge of treating cancer of the cervix to this deliberation. The value of lymphadenectomy for curing node metastasis from carcinoma of the cervix is roughly 30%-50% but for adenocarcinoma of the corpus, the result is more disappointing for it drops from 25% to 30% [12,13]. Still a cure rate with positive nodes in one fourth to one third of the patients with adenocarcinoma of the endometrium is not insignificant, and is especially important to the fortunate individual who was cured by excising node metastasis, and in a small way, these additional cures contribute to the overall salvage of this cancer. These predictions for improvement depend upon a small operative mortality; otherwise, the success will be erased by another form of treatment failure. The question of whether radical hysterectomy can be applied safely and ef-
334
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ficiently is of major concern. The adverse physical features and poor health of patients with carcinoma of the endometrium will disqualify many patients for radical hysterectomy. Obesity imposes more hazards for complications while the scope of the resection is compromised. Greater age and associated infirmities fail many patients after the postoperative evaluation. Thus, a large portion of those who most need additional radicality of therapy will be unsuitable for operation. Unless we can assure higher incidence of operability and a low primary mortality, the promise of markedly improved cure rates for all patients with adenocarcinoma of the endometrium by more frequent use of radical hysterectomy dims. For those patients who are a greater risk for metastasis and are physically suitable, there is the potential of benefit. Whether it is an attempt to apply radical hysterectomy as routinely as possible or on an individual basis may be decided by our ability to identify those patients who need more extended resection. To support the radical hysterectomy as a more standard therapy, there should be supporting evidence that spread to the upper vagina, parametrium, and regional nodes is a common cause for failure by the more standard conservative hysterectomy. What proportion of the disease in carcinoma of the endometrium is stage II and III. Certainly there should be a high incidence to justify a more radical resection.
Radical
Hysterectomy
for Corpus et Endocervicis
(stage II)
We should consider stage II first for extension to the cervix has the most popular support for radical hysterectomy and presents three sites for greater potential metastasis which would not be adequately included in the conservative hysterectomy. Frequent parametrial and upper vaginal and pelvic wall node metastasis makes the stage II patient a more likely candidate for the radical hysterectomy. The proportion of stage I and stage II disease varies surprisingly among different series of patients from 6% to 20% (Table I). This range of incidence figures may seem to reflect upon our ability to clinically stage the disease and could be used as an argument for wider resection of stage I disease to assure adequacy; however, several factors may influence the ratio of early to late stages among various series of patients reviewed. The population which comprises the series, the motivation of the patients to seek medical attention early, the economic means to obtain the diagnostic testing, and the medical program provided for them for early detection are factors which raise the proportion of stage I and lower the incidence of stage II and III. This range in frequency may be due to an inconsistent clinical staging. To suggest that this variation in the ratio to stage I to II could be due to different techniques for establishing the diagnosis is only speculative; however, the readiness with which the diagnosis is made depends upon the clinical evidence of spread to the cervix and the thoroughness with which a search is made. An accurate diagnosis for those patients who have a lesion on the cervix can be made by biopsy directed at the clinically apparent lesion. There are additional patients with stage II cancer of the endometrium for whom the cervix
RADICAL
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TABLE I ADENOCARCINOMA ENDOMETRIUM FREQUENCY OF CORFVS ET CERVICIS Author
Year
Roberts Gusberg Hawksworth Morris Carmichael Rickford Kotlmeier Lee Neilsen and Koller Sal1 et al. Moltz et al. Karlstedt Boronow (MDAH)” Davis Lewis et al. Frick MDAH
1961 1964 1964 1967 1967 1968 1969 1969 1969 1970 1972 1968 1969 1964 1970 1973 1973
a The
University
of Texas
System
Cancer
Number
CANCER
STAGE
II
of patients
% Stage
281223 40/518 271345 71265 58l693 9150 133/1123 14/150 1531634 10/307 81169 103/1165 631270 751525 221129 221348 1091737 Center
M. D. Anderson
335
13 8 8 3 10 18 11 9 24 3 5 9 23 14 17 6 15 Hospital
and Tumor
Institute.
appears grossly normal, and for these a routine biopsy of the portio of the cervix and a fractional curettage of the endocervical canal would detect the subclinical metastasis. If applied routinely, these tests are more likely to establish the true condition of the lower segment of the uterus; the reverse may be true if certain precautions are not practiced [2,5,8,14]. False positive specimens may be obtained by fractional curettage as contaminants by fragments of cancer from the corpus, or by a polyploid portion of the corpus cancer extending down into the endocervical canal. Although this is not likely to occur often, it would influence the frequency ratio of stage I to stage II. Whether curettage alone is accepted by the clinician as a single evidence of spread to the cervix or discounted would influence the incidence of stage II. The care by which the corpus is excluded before fractional curettage by inserting a gauze plug to the level of the internal OSmay lower the incidence of some series by eliminating false positive specimens. Likewise, the true condition of the cervix will be confirmed if the histologic specimen contains adenocarcinoma growing in relationship to the endocervical glands or endocervical stroma. When consideration is given to all these factors for establishing spread to the cervix, the portion of patients with early stage I still dominates. If we accept the occurrence incidence range of 15%-20% of the patients with endometrial cancer as having spread to the cervix, we see that the frequency alone would not justify routine radical hysterectomy for all patients with adenocarcinoma of the endometrium. Yet stage II may remain an indication for individualized treatment by radical hysterectomy in about one fifth of
336
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the patients. We need not conclude that the different ratios from stage I to stage II among various series reported reflect seriously upon our ability to clinically identify spread to the cervix. Only a few patients with stage I prove to be more advanced by examination of the surgical specimen 1151. When care is taken to sample the cervix and lower uterine segment, there is consistency between the clinical appraisal and the findings at the time of operation and histologic study of the specimen. The role for radical hysterectomy and lymphadenectomy seems established for stage II patients where the frequency of metastasis beyond the uterus warrants treating all stage II patients as if the metastasis was established. Treatment by radical hysterectomy is most popular for stage II adenocarcinema of the endometrium, and with this stage, more information is available about 5 yr survivals and incidence of metastasis. Although the 5-yr cure rates for stage II treated by extended surgery range from some 20% to 50% among the reports reviewed, the success rate with radical hysterectomy generally is superior, Although we expect the modern irradiation therapy methods to show improvement with the new megavoltage equipment, the evidence is not yet conclusive. At present, the radical hysterectomy has a strong position in the treatment of stage II lesions, but much less secure in the treatment of stage I. The literature provides few statistics with the results of radical hysterectomy for stage I carcinoma of the endometrium. The preponderance of reports available are concerned with those patients treated by conservative hysterectomy and irradiation. In addition, from the material available, a comparative evaluation of radical hysterectomy is not possible in many instances because operability rates for the series using radical hysterectomy indicates much selectivity. There is some information provided about the cure rates obtainable by radical hysterectomy from series in which all patients are included. Radical
Hysterectomy
for Corpus
(Stage I)
Any superiority of radical hysterectomy over the conventional hysterectomy for stage I lesions would indicate that the patient did have metastasis removed by the more extended operation. We recognize a spread pattern from the corpus to the regional nodes without the necessity of the involvement of the cervix. Since the corpus lesion is adequately treated by conservative hysterectomy, to advise radical hysterectomy with associated lymphadenectomy for stage I expresses a concern for metastases to the regional nodes. The incidence of positive nodes for stage I adenocarcinoma of the endometrium averages about 10% (Table II). The higher incidence of figures ranging up to 24% for some series can usually be explained by selection of patients with a greater risk for positive nodes or by counting patients whose nodes were removed only because they were abnormal. It is apparent that the frequency of positive nodes for stage I carcinoma of the endometrium will not justify routine lymphadenectomy; however, lymphadenectomy may well be a useful treatment if by selectivity the patients with a greater risk for node metastasis can be identified, The incidence of me-
RADICAL
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ENDOMETRIAL
337
CANCER
II
ENDOMETFUAL CARCINOMA FREQUENCY OF LYMPH NODE METASTASES Patients positive Author Randall Bmnschwig Liu and Meigs Lefevre Schwartz and Brunschwig Roberts Andersen and Stephens Barber et al. Davis Parsons Hawksworth Winterton Rickford Lees Morris Lewis Stallworthy
Year
No.
1950 1954 1955 1956 1957 1961 1961 1962 1964 1959 1964 1964 1968 1969 1967 1970 1973
4120 lOj57 11147 7145 13196 10/34 4152 12185 7156 4150 8164 8176 5150 13/76 4/21 17/129 18/131
with nodes % 20% 17% 23% 16% 14% 29% 8% 20% 12.5% 8% 12.5% 10% 10% 17% 20% 13.2% 14%
Stage Not
I
stated
Stage Not
II
stated
4133 12% Not stated
7114 50% Not stated
5122 23% Not stated
218 25% Not stated
Not
Not
stated
6/11 2136 3156 16 12/107
stated 18.7%
219
418 11.2%
5 5122 23% 11127 40%
tastasis to the regiona nodes is increased when the histologic pattern of the carcinoma is undifferentiated and penetration of the cancer into the uterine wall is deep [Z&16]. Under these conditions, the incidence of regional nodes is increased to a frequency that requires treatment either by lymphadenectomy or irradiation.
Results
(Findings)
Table III presents some example reports of treatment results employing varied methods. For some authors both the absolute and the corrected 5-yr survivals are presented. From the representative reports the inadequacies of current treatment of adenocarcinoma of the endometrium are evident and show that we should not be complacent, but instead, strive to better our treatment of this disease. The reports which give results of treatment of radical hysterectomy are presented in Table IV. The 5-yr survival statistics are generally superior. Since patients with adenocarcinoma of the endometrium are poor candidates for operation, the operability percentages shown in Table V are of practical interest. When selection is liberal, a larger percentage of the poor-risk patients and those with more advanced spread may be judged operable. One wonders about the number of operative deaths, and notes in Table VI that the primary mortality for radical hysterectomy is not significantly greater than those experienced in other reports employing conservative hysterectomies. This may suggest that, if a patient can tolerate laparotomy, her postoperative course may
338
FELIX
RUTLEDGE TABLE
TREATMENT
III
ADENOCARCINOMA ENDOMETRIUM 5-Yr
Author
survival
Year
No. Pts.
Absolute
Whetham Ingiulla Moltz et al. Bastiaanse Roberts Parsons Gusberg Hawksworth
1972 1968 1972 1952 1961 1959 1964 1964
257 22/112 169 2171264 223 62 2901518 167/243
58.3% 73.2% 72% 72.5% 1431223 (23/33) 78% 55.9% 69%
Anderson Carmichael Wade et al. Karlstedt Keller Lewis and Stallworthy
1964 1967 1967 1968 1969 1970
52 3981603 265 1123 4091634 252
83% 66% 67.5% 61% 64.6% 68.2%
Sal1 Stallworthy Frick Schlink
1970 1970 1973
307 131 348 3651465
68195 = 71.6% 66.1% 60%
a Corrected
= death
from
intercurrent
Corrected’
Year
Radical hysterectomy plus lymphadenectomy Schwartz and Brunschwig” 1957 Parsons 1959 Winterton 1959 Roberts 1961 Lees 1969 Rickford” 1968 Lewis 1970 Stallworthy 1970 Total hysterectomy plus lymphadenectomy Andersen and Stephens 1964 LefevreC 1956 Davis 1964 o Brunschwig advocated radical b Full Wertheim all patients. c Advocated radical hysterectomy.
hysterectomy
Vaginal
hysterectomy
60.4%
Radical hysterectomy lymphadenectomy 85% 72.6% 69% Radical hysterectomy, 129 patients, 71.5% 68% 73%
diseases
not counted.
TABLE
IV
ADENOCARCINOMA ENDOMETFUUM TREATMENT
Author
Vaginal
BY EXTENDED OPERATION
Absolute 5-yr survival
No. pt
37
129 131
2.8137 73% 78% 76% Not 63% Not 71.5% 68/95 71%
52 42 151
83% Not 68.5%
99 27 76
hysterectomy.
Corrected 5-yr survival
81.5% 84.0%
Selection
Selective (26%) Selective Consecutive
given Consecutive Consecutive Consecutive
given
85% given
Consecutive Consecutive Selective
+
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TABLE V OPERABILITY Inguilla Andersen and Stephens Lees Bastiaanse Wade et al. Hawksworth Roberts Rutledge Winterton Rickford
5961573 52171 76/150 2521264 2451265 2211243 271223 5161737 89190 1521174
88.3% 74% 50% 96.2% 85.7% 91% 12% 70% 95% 87%
be as safe with radical hysterectomy and lymphadenectomy, or lymphadenectomy alone, as with conservative hysterectomy only. Perhaps our fears of the increased hazards of radical hysterectomy above those of the conservative hysterectomy are not founded in these experiences. Treatment
Results
(Stage ZZ)
The indication for radical hysterectomy in adenocarcinoma of the endometrium stage II seems better supported for several reasons already mentioned. The results are noted in Table VII. Just as the incidence of stage II ranges widely among authors, the presented survival also varies widely. The various degrees of advanced cancer and amounts of metastatic cancer may be the explanation. The rigidity by which the criteria for operability are applied and the preoperative search for metastases will influence treatment results. The TABLE VI COMPLICATIONS
Year
Size of series reported
Liu Meigs Brunschwig
1955 1957
57
Parsons
1959
62
Winterton Andersen and Stephens Roberts Davis Lees Lewis and Stallworthy Rutledge Ingiulla Rickford
1959 1961 1961 1964 1969
Author
a Op.
mort.
= postoperative
1973 1968 1968 mortality.
99 52 27 56 R.H. 76 R.H. 129 5231737 5031573 50
+ La.
Complications l/60 op. mart.” 1.6% Fistulas (6/57) 11%; op. mort. 2196 = 2.2% Fistulas (S/60) 8%; atony and incontinence 12%; 27% postop. complications Op. mort. 3/99; one fistula No op. mort.; no fistulas Op. mort. 2/27 = 7%; no fistulas Op. mort. l/2%; 1.5% fistulas Op. mort. 2/76; 2.6% pul. emb. Op. mort. 3/129 = 2.3% Op. mort. 1 = 3% Op. mort. 2% Not given
340
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TABLE VII ADENOCARCINOMA ENDOMETRIUM SURVIVAL CORPUS ET CERVICIS (STAGE II) Author
Year
Schwartz and Brunschwig Roberts Gusberg Hawksworth Davis Wade et al. Kottmeiei Neilsen and Koller Sal1 Moltz et al. Kalstedt Boronow Lewis et al. Frick
1957 1961 1964 1964 1964 1967 1969 1969 1970 1972 1968 1969 1970 1973
a Kottmeier
No. pt. surviving 12137 19128 11/40 5117 19/81 7 581133 4/153 5/10
318 451103 63 13122 8122
% Survivals 42% 68% 27.5% 29% 24% 9.4% 44% 26% 50% 38% 44% 60% 60% 36.4%
corrected = 51%
series which depends upon clinical examination to identify metastasis will generally have more advanced cancers in the stage II category. More curable patients in stage II will be diagnosed before treatment only when a search for the subclinical metastasis by cervical biopsy and fractional curettage is a routine practice. Whether the report represents clinical or surgical staging becomes important. The differences in clinical staging (FIGO) and the clinicopathological (clinical staging altered by findings at laparotomy and pathological study of the specimen) could explain some reports with unusually good outcome. More accurate interpretations and conclusions of reports would be helped if a single method for staging was employed or if results of both clinical (FIGO) and clinicopathological staging were supplied by the author. Generally, the accomplishments for radical hysterectomy as a treatment for endometrial carcinoma are commendable and help secure a role for this method of treatment.
Treatment
Results
(Stage I)
The results of the management of stage I patients by radical hysterectomy have been successful in diminishing the incidence of vaginal recurrence, but the results with conservative hysterectomy and preoperative irradiation of the upper vagina have been equally successful and more easily accomplished. Most will agree that this is not a strong argument for employing radical hysterectomy in stage I disease and will agree that preoperative irradiation will sterilize subclinical metastasis about the upper vagina preventing local recurrences after conservative hysterectomy for adenocarcinoma of the endometrium. Fewer clinicians are convinced that the external therapy will accomplish the same for nodal metastasis; therefore, the dominant remaining need for extending operation in stage I is lymphadenectomy. Control of the
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CANCER
cancer which has metastasized to the pelvic nodes by operation also has skeptics. A sampling of the reports for the past 25 yr shows that the pelvic lymphadenectomy has not been popular; although several centers have some experience, even the largest of the series represents fewer than 100 patients. This becomes especially significant when the total number of patients treated by these same authors numbers into several hundreds. The curability of positive nodes may be noted in Table VIII to range from 15% to 35%.
Complications
of Treatment
The radical hysterectomy introduces the risk of postoperative urinary tract complications. It increases the dangers of hemorrhage and infection after hysterectomy and because the duration of the operation and recovery are lengthened, the complications of the cardiovascular and respiratory systems must be more frequent. Yet the tolerance as indicated by Table VI seems acceptable. The first listing in the table represents the complications of radical hysterectomy; next are those of total hysterectomy and lymphadenectomy; and lastly, those of conservative hysterectomy alone. These statistics would suggest that with properly chosen patients and expertly performed surgery the radical hysterectomy can be employed safely.
Conclusions
Excerpted
from the Literature
Lees (1969, Sheffield, England) reported 14 yr of his experience performing radical hysterectomy consecutively on 150 patients. This represents all the patients seen in all stages. Although he was dedicated to applying this operation consecutively, only 76 of 150 had the radical hysterectomy and lymphadenectomy. Lees concluded: “The evidence from this consecutive and unselected group indicates that the true incidence of positive nodes is at least 20 per cent. All the evidence indicates that surgery should be the primary treatment and that it must be radical to prevent recurrences.” Lees believed that “an extended radical hysterectomy and hemi-vaginectomy is the best procedure, that to attempt the Wertheim hysterectomy is a mistake. Lymphadenectomy gave no improvement in results in this series and the prognosis in gland positive cases was poor. Postoperative X-ray therapy TABLE
ADENOCARCINOMA ENDOMETRIUM Schwartz and Brunschwig Javert Parsons Lees Andersen and Stephens Barber Wade et al. Dobbie et al. Boronow Lewis et al. Total
1957 1952 1959 1969 1961 1962 1967 1965 1964
1970
VIII
SURVIVAL OF PATIENTS WITH POSITIVE NODES 2112 17% 5 yr 4114 28% 3-l/2 yr 214 2 yr; l/4 3 yr l/9 5 yr l/4 25% 5 yr 14/17 dead; l/17 lost; O/4 5 yr 417 5 yr O/S 5 yr 4111 5 yr 13168 20% 5 yr
l/17
5 yr;
l/17
10 mo
342
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has been adopted to replace the lymphadenectomy; however, note is made of suspicious node groups to aid the radiotherapists in directing the treatment.” Roberts (1961, Chelsea Hospital, London) reported a series of 27 patients who had radical hysterectomy for special indications selected from 223 patients admitted. The majority were treated with preoperative radium plus conservative hysterectomy as the standard treatment. “From the preceding results the operation of choice , . . (after preoperative intracavitary radium) . . . would appear to be total hysterectomy and bilateral salpingo-oophorectomy but if the operative scope is to be widened then there are reasonable grounds for performing Wertheim hysterectomy. This is especially true if there are grounds for suspecting that the cervix is involved.” Parsons (1959, Boston) concluded that the end results in this study compare favorably to those reported in the current literature and justifies further evaluation of the radical surgical approach for the treatment of endometrial carcinoma. “. . . it is hoped that future experience and observation . . . will improve the selection of patients and reduce mortality, at which time the Wertheim hysterectomy and lymphadenectomy may prove worthy of more routine use.” “Mention must be made of the discouragingly high rate of urinary tract complications. This problem, which has been difficult to solve, has precluded routine use of adequate radical surgery in the elderly, poor risk patient with endometrial carcinoma.” Lewis and Stallworthy (1970, Oxford, England): “Granted that the pelvic glands are involved in between 1 in 5 and 1 in 10 women, it would seem quite unnecessary to perform extended surgery on the majority of patients.” “The practical problem, therefore, is to find a way of selecting those patients at maximum risk of nodal spread and to plan the treatment most likely to be effective for the whole field at risk.” I‘ . . * surgical excision of the lymphatic nodes plus postoperative irradiation has had a favorable influence on prognosis.” Gusberg (1962) stated: “The rate of cure will be meager in those in whom nodes are positive. Nonetheless the wide dissection encouraged by the radical operation should permit an operative coverage of the lymphatics but not otherwise possible.” Gusberg recognized a role for extended operation in the treatment of adenocarcinoma, and the frequency with which it is prescribed should be decided for each patient. He plans for individualization of treatment by selecting the most effective methods for the therapeutic problems. From Stallworthy’s consecutive series of 136 patients, he arrived at four practical points of clinical interest, and these serve as an indicator that the field at risk of patients with adenocarcinoma of the endometrium increases with the stage of the disease. In the series, stage II, spread to the cervix occurs in 10% of the patients; positive nodes occur in 14% of all stages; the adnexae are involved in 5%; and in the vagina, 2%. This report provides information not previously available; thus, this article is recommended for detailed study.
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343
TABLE IX THE M. D. ANDERSON HOSPITAL AND TUMOR INSTITUTE CONSERVATIVE HYSTERECTOMY AND LYMPHADENECTOMY [103 Patients with Stage I (71), 11 (24), III (8)] Nodes negative Nodes positive Positive pelvic only Positive aortic only
97/103 6/103 4/103 21103
= = = =
94% 6% 4% 2%
a No survivals of patients with positive nodes.
Perhaps Professor Stallworthy has acquired a depth of clinical judgment while treating this series of patients which would satisfy our questions about this topic. Stallworthy’s conclusions are: Radical hysterectomy is advised for all patients with stage II lesions. For stage I patients with a well differentiated histology, the operation of choice is conservative hysterectomy; however, lymphadenectomy will be performed if the uterine specimen demonstrates deep myometrial penetration. If in stage I the tumor is poorly differentiated, a Wertheim hysterectomy and lymphadenectomy is performed as the treatment of choice. Patients who are found to have positive nodes receive postoperative X-ray therapy. Stallworthy showed that radical hysterectomy can be applied to a higher percentage of the patients with endometrial carcinoma in both stage I and stage II disease with 131 patients treated consecutively by Wertheim operation with lymphadenectomy. A 14% positive node incidence was encountered for the total series. There were 27 patients with stage II disease, yielding a 41% positive node recovery. The results are excellent for treating stage II lesions -a 5-yr cure rate of 59%. Stallworthy suggested that the treatment for stage II adenocarcinoma of the endometrium may be promptly decided in favor of the intracavitary radium and Wertheim hysterectomy with lymphadenectomy. For stage I lesions, however, the low incidence of metastases for the well-differentiated tumor makes it possible to treat these patients by conservative hysterectomy. When the histologic pattern is undifferentiated, the Wertheim hysterectomy and lymphadenectomy is advocated. We at the M. D. Anderson Hospital have not consistently practiced radical hysterectomy for either stage I or stage II lesions, preferring irradiation therapy and a conservative hysterectomy. An occasional patient has required radical hysterectomy when the anatomy was not suitable for intracavitary radium application. We have had some experience with conservative hysterectomy and lymphadenectomy (Tables IX and X). The development after lymphadenectomy of pelvic wall lymphocysts and added posttreatment fibrosis were the most frequent postoperative complications. These events which threatened ureteral obstruction and chronic leg edema diminished enthusiasm for the procedure, especially after no patients with node metastasis were cured. In addition, the lymphadenectomy prolonged the operation and recovery, conditions undesirable for this group of patients who were less suited physically for surgery.
344
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X
ADENOCARCINOMA ENDOMETRIUM THE M. D. ANDERSON HOSPITAL TREATMENT Stage IA IA IB II III-IV Postop. Depth muscle
Grade
Treatment
I II-III -
Hysterectomy Radium + hysterectomy W.P.a + radium + hysterectomy W.P. + radium + hysterectomy W.P. + radium
invasion ~5% Thickness > 50% Thickness
a Whole-pelvis
Vaginal radium W.P. + vaginal
radium
irradiation.
CONCLUSIONS About 1950 the radical hysterectomy had a surge of new popularity for carcinoma of the cervix, and shortly after this greater use of the radical hysterectomy and lymphadenectomy for endometrial carcinoma was suggested [17]. For several reasons, the more routine use of the radical hysterectomy did not prove feasible. Although the operation is eminently suitable for patients with certain conditions of endometrial carcinoma, the combination of conservative hysterectomy and irradiation found a greater usefulness for the majority. There is no evidence to warrant changing these conditions because: 1. Irradiation methods have improved for dosage and distribution, and when added to conservative hysterectomy, the range is expanded to equal the radical hysterectomy. 2. The high cure rate presently being obtained by conservative hysterectomy indicates that most patients do not need the more hazardous radical hysterectomy. 3. The older-aged patients with associated diseases limit the applicability of radical hysterectomy, often for the patient who needs surgical resection most. 4. Direct pathways to aortic nodes limit effectiveness of eliminating lymph node metastases by lymphadenectomy. A canvass of the reports available in the literature for analysis in whichconsecutive patients were treated with radical hysterectomy provides a very limited basis for assessing the effectiveness of this treatment. Because the number of patients is small, and selectivity makes judgment of the outcome difficult and what happened to the rest of the series is often not provided. Some additional information on the subject can be found among reports in which radical hysterectomy is employed selectively among some patients while the majority are treated with the more conservative hysterectomy. From both sources of information, an answer to several questions about radical hysterectomy to provide a wider resection for adenocarcinoma of the endome-
RADICAL
HYSTERECTOMY
IN
ENDOMETRIAL
345
CANCER
trium can be obtained. Considering only surgical treatment, the conservative hysterectomy is still adequate for the majority of patients’ needs. The percentage of clinical stage I disease in most series is usually more than two thirds the total number. The relative accuracy of the clinical staging is confirmed because removal of the uterus alone will produce a S-yr survival of 80%. Still better survival may be possible, for some stage I patients die because metastases are not included in the treatment. Inability to exclude metastases before treatment prevents a positive statement that none of the patients with stage I would need radical hysterectomy or lymphadenectomy. If we propose to employ extended hysterectomy more liberally, then we must make a decision as to whether to apply it as a routine procedure or selectively on the basis of individual needs. Beecham [ 181 has suggested that radical hysterectomy should be applied routinely and that the disease, adenocarcinema of the endometrium, will benefit if all the patients with the more favorable lesions are treated more radically. Another opinion [8,16] suggests that the radical hysterectomy be prescribed on a more individual basis noting that the incidence of positive nodes in stage I is quite infrequent when the tumor is well differentiated and without muscular wall invasion. These patients with the more favorable lesions will not benefit, and they would be sub jetted unnecessarily to the hazards of the more extended operation. This more conservative approach is supported by the high curability rates of stage I lesions. Still a third philosophy of treatment of adenocarcinoma of the endometrium as practiced by the staff at The University of Texas System Cancer Center M. D. Anderson Hospital employs irradiation to expand the range of the therapy beyond that capable of conservative hysterectomy. To support this plan, one must be confident in the effectiveness of irradiation therapy to destroy metastatic sites of adenocarcinoma both in the parametrium and the upper vagina and pelvic wall nodes (Tables X and XI). There is no reason to doubt that irradiation will sterilize a metastasis which is small. The characteristics of the disease which may indicate the need for a radical hysterectomy and lymphadenectomy are also indicators for a wider range of treatment by irradiation provided by external therapy. For example, patients with an enTABLE
XI
ADENOCARCINOMA ENDOMETRIUM THE M. D. ANDERSON HOSPITAL 1948-1969 RESULTS OF TREATMENT 5-yr Clinical
Total
stage
I II III IV Total u Includes
cases 516 118 70 33 737
death
from
all causes.
survival”
No.
%
367 52 13 1 433
71.1 44.0 17.0 3.0 58.8
346
FELIX
RUTLEDGE
larged uterus and a microscopic pattern of undifferentiated tumor are a signal for intensive preoperative external therapy combined with intracavitary radium. A diminished dose is, of course, necessary because the external therapy contributes to the limits of tolerance. Those patients with stage II adenocarcinema of the endometrium with the clear need for more extended treatment of the primary and pelvic wall nodes should receive more extensive preoperative X-ray therapy followed by conservative hysterectomy. It is not suggested that the more intensive preoperative irradiation therapy be combined with radical hysterectomy, for in our experience such a plan induces intolerable complications. Although we suggest that external therapy will accomplish the same as extended surgical resection, still there is a role for radical hysterectomy in this scheme. For patients who present conditions which conflict with the use of external therapy or have an anatomical problem which is expected to hamper the effectiveness of irradiation therapy, it would seem logical to advocate radical hysterectomy. REFERENCES 1. ROBERTS, D. W. T., Carcinoma of the body of the uterus at Chelsea Hospital for Women, 1943-1953, J. Obstet. Gynaecol. Brit. Commonw. 68,132-138 (1961). 2. PARSONS, L., AND CESARE, F., Wertheim hysterectomy in the treatment of endometrial carcinoma, Surg. Gynecol. Obstet. 108,582-590 (1959). 3. LEFEVRE, H., Node dissection in cancer of the endometrium, Surg. Gynecol. Obstet. 102, 649-656
(1956).
4. SALL, S., SONNENBLICK, B., AND STONE, M. L., Factors affecting survival ofpatients with endometrial carcinoma, Amer. J. Obstet. Gynecol. 107, 116-123 (1970). 5. WINTERTON, W. R., Discussion on carcinoma of the body of the uterus, Proc. Boy. Sot. Med. 47,897-899 (1954). 6. RICKFORD, R. B. K., Involvement of pelvic lymph nodes in carcinoma of the endometrium, 1. Obstet. Gynaecol. Brit. Commonw. 75,580 (1968). 7. LEES, D. H., An evaluation of the treatment of carcinoma of the body of the uterus. J. Obstet. Gynaecol. Brit. Commonw. 76,615-623 (1969). 8. STALLWORTHY, J. A., Surgeru of endometrial cancer in the Bonney tradition, Ann. Roy. Coil. Surg. Engl. 48,293-305 (1971). 9. JAVERT, C. T., Spread of benign and malignant endometrium in lymphatic system with note on coexisting vascular involvement, Amer. J. Obstet. Gynecol. 64, 780-802 (1952). 10. SCHWARTZ, A. E., AND BRUNSCHWIG, A., Radical panhysterectomy and pelvic node excision for carcinoma of the corpus uteri, Surg. Gynecol. Obstet. 105,675-680 (1957). 11. LIU, W., AND MEIGS, J. V., Radical hysterectomy and pelvic lymphadenectomy, Amer. J. Obstet. Gynecol. 69, 1-32 (1955). 12. LEWIS, B. V., STALLWORTHY, J. A., AND COWDELL, R., Adenocarcinoma of the body of the uterus, J. Obstet. Gynaecol. Brit. Commonw. 77,343-348 (1970). 13. DOBBIE, B. M. W., TAYLOR, C. W., AND WATERHOUSE, J. A. H., A study of carcinoma of the endometrium, J. Obstet. Gynaecol. Brit. Commonw. 72,659-673 (1965). 14. BORONOW, R. C., Carcinoma of the corpus: treatment at M. D. Anderson Hospital, in Cancer of the uterus and ovary, Year Book Publ., Chicago, pp. 35-61 (1969). 15. FRICK, H. C., MUNNELL, E. W., RICHART, R. M., BERGER, A. P., AND LAWRY, M. F., Carcinoma of the endometrium, Amer. 1. Obstet. Gynecol. 115,663-675 (1973). 16. GUSBERG, S. B., AND JONES, H. C., Selection of treatment for corpus cancer, Amer. J. Obstet. Gynecol. 80,374-379 (1960). 17. RANDALL, C. L., Letter to the editor: Panhysterectomy for uterine carcinoma, Amer.J. Obstet. Gynecol. 59,942 (1950).
FUDICAL
HYSTERECTOMY
IN
ENDOMETRIAL
CANCER
347
18. BEECHAM, C. T., Discussion of FRICK, H. C., MUNNELL, E. W., RICHART, R. M., BERGER, A. P., and Lawry, M. F. Carcinoma of the endometrium, Amer. J. Obstet. Gynecol. 115, 674 (1973). 19. ANDERSEN, J. L. C., AND STEPHENS, S. R., Survival in carcinoma of the endometrium following pelvic node dissection, Dan. Med. BUZZ. 11, 160-164 (1964). 20. BARBER, K. W., JR., DOCKERTY, M. B., AND PRATT, J. H., A clinicopathologic study of surgically treated carcinoma of the endometrium with nodal metastasis, Surg. Obstet. Gynecol. 115,568-573 (1962). 21. CARMICHAEL, J. A., AND BEAN, H. A., Carcinoma of the endometrium in Saskatchewan, Amer. J. Obstet. Gynecol. 97,294-307 (1967). 22. DAVIS, E. W., JR., Carcinoma of the corpus uteri, Amer. J. Obstet. Gynecol. 88, 163-170 (1964). 23. DELCLOS, L., AND FLETCHER, G. H., Malignant tumors of the endometrium: evaluation of some aspects of radiotherapy, in Cancer of the uterus and ouay, Year Book Publ., Chicago, pp. 62-72 (1969). 24. DEMUELENAERE, G. F. G. O., The case against Wertbeim’s hysterectomy in endometrial carcinoma, J. Obstet. Gynaecol. Brit. Commonw. 80,728-734 (1973). 25. FLETCHER, G. H., RUTLEDGE, F. N., AND DELCLOS, L., Adenocarcinoma of the uterus, Front. radiat. ther. oncol., Vol. 5, S. Karger AG, Basel, pp. 262-275 (1970). 26. GUSBERG, S. B., AND YANNOPOULOUS, D., Therapeutic decisions in corpus cancer, Amer. J. Obstet. Gynecol. 88,157-162 (1964). 27. HAWKSWORTH, W., The treatment of carcinoma of the body of tbe uterus, Proc. Roy. Sot. Med. 57,467-471 (1964). 28. INGIULLA, W., AND COSMI, E. V., Vaginal hysterectomy for the treatment of cancer of the corpus uteri, Amer. J. Obstet. Gynecol. 100,541-543 (1968). 29. KARLSTEDT, K., Carcinoma of the uterine cervix, factors bearing on the curability, Acta Radial. Suppl. 282 (1968). 30. KOTTMEIER, H. L., Carcinoma of the corpus uteri: diagnosis and therapy, Amer. J. Obstet. Gynecol. 78,1127-1140 (1959). 31. KOTTMEIER, H. L., Individualization of therapy in carcinoma of the corpus, in Cancer of the uterus and ouay, Year Book Publ., Chicago, pp. 102-108 (1969). 32. MOLTZ, A., POMERANCE, W., AND STREISFELD, S., Adenocarcinoma endometrium, Obstet. Gynecol. 39, 199-201 (1972). 33. MORROW, C. P., DISALA, P. J., AND TOWNSEND, D. E., Current management of endometrial carcinoma, Obstet. Gynecol. 42,399-406 (1973). 34. NG, A. B. P., AND REAGAN, J. W., Incidence and prognosis of endometrial carcinoma by histologic grade and extent, Obstet. Gynecol. 35,437-443 (1970). 35. NILSEN, P. A., AND KOLLER, O., Carcinoma of the endometrium in Norway 1957-1960 with special reference to treatient results, Amer. J. Obstet. Gynecol. 105, 1099-1109 (1969). 36. SCHLINK, H., Cancer of the female pelvis, J. Obstet. Gynecol. Brit. Commonw. 67,402410 (1960). 37. ULFELDER, H., Advances in therapy of carcinoma of the uterine body and cervix, Acad. Med. N. J. BUZZ.8,201-206 (1962). 38. VAN BOUWDIJK BASTIAANSE, M. A., Cancer of body of uterus, J. Obstet. GynecoZ. BTit. Commonw. 59,611-616 (1952). 39. WADE, M. E., KOHORN, E. I., AND MORRIS, J. McL., Adenocarcinoma of the endometrium, Amer. J. Obstet. Gynecol. 99,869-876 (1967). 40. WHETHAM, J. C. G., Carcinoma of the endometrium, Amer. 1. Obstet. Gynecol. 112,339-343 (1972).
ONCOLOGY
2,331-347
(1974)
The Role of Radical Hysterectomy in Adenocarcinoma of the Endometrium FELIX The M. D. Anderson
University Hospital
RUTLEDGE, of Texas & Tumor
Received
M.D.
System Cancer Center Institute, Houston, Texas
March
77025
18,1974
A retrospective assessment of treatment results for patients with adenocarcinoma of the endometrium shows little progress for the past 20 yr in management of this disease. These accomplishments may have been affected adversely by the increased number of elderly patients treated within recent years, for the prognosis worsens with advanced age. Likewise, because women are living longer, more enter the age when adenocarcinoma of the endometrium is prevalent, increasing the frequency of this disease. Thus, gynecologic oncologists have become aware that the treatment problem for adenocarcinoma of the endometrium deserves more research for methods to improve survival. The primary lesion is readily curable by hysterectomy. Therefore, it is the metastases which need better therapy. For this purpose, megavoltage irradiation therapy is being used more often to supplement intracavitary radium. However, the role of radical hysterectomy has been reconsidered. A review of the experiences with radical hysterectomy has been summarized from the literature and the conclusions presented.
Compared with cancer at other sites within the body, treatment of cancer of the endometrium is notably successful; yet for some patients, treatment is either misdirected or inadequate because regrowths appear within the pelvie region. A recurring question about the management of carcinoma of the endometrium is why should we not use radical hysterectomy more often. As we consider the question, several additional ones are generated, such as (1) What can be expected technically of the radical hysterectomy which cannot be accomplished by conservative hysterectomy? The obvious answer is wider local resection of the primary lesion and the additional excision of regional nodes. (2) Is metastasis to the upper vagina, parametrium, and the regional nodes sufficiently common to include resection of these tissues routinely? Although we recognize these sites as locations for metastasis from cancer of the endometrium, we need proof that this is a problem in treatment for most of the patients. To resolve the question about the greater role of radical hysterectomy in adenocarcinoma of the endometrium, we must first prove a need to replace conservative hysterectomy with a procedure that resects more widely. We must review the records of those patients who were treated by conservative hysterectomy to decide if failure to cure is often because metastases exist beyond the range of the conservative hysterectomy but within the bounds of the more extended radical hysterectomy. To resolve the question concerning such inadequacies of the conservative hysterectomy, the sites of first appear331 Copyright All rights
@ 1974 by Academic Press, Inc. of reproduction in any form reserved.
332
FELIX
RUTLEDGE
ante of recurrent adenocarcinoma in those patients who are not cured need investigation. A study of the treatment failure sites or locations of the first recurrence should point to the deficiencies of the current standard method of treatment without radical hysterectomy. If recurrences appear commonly within the pelvis after our standard therapy, and if the weaknesses can be corrected by wider resection, then we should consider using radical hysterectomy more often. (3) Do the experiences recorded in the literature prove that radical hysterectomy benefits by this wider excision of the primary and regional nodes? In these reports we should look for the conditions of the disease for which radical hysterectomy improves cure rate. Do patients in both stage I and stage II adenocarcinoma of the endometrium benefit, or only the more advanced stage II and III? To decide the role of radical hysterectomy as a part of an individualized treatment plan, we should also study the reports and outcome of those patients treated by lymphadenectomy without the extended hysterectomy since lymphadenectomy is an important part of the plan for more extended operation. Since cure rates will be the guide to the effectiveness and to the specific accomplishment of excising metastasis, we should note the outcome of those patients who have positive nodes excised. How many patients are cured by excising positive nodes? (4) Can the radical hysterectomy be performed upon patients with adenocarcinoma of the endometrium with safety? Clearly, if we are transferring our opinion of the radical hysterectomy from our experience with its use in patients with carcinoma of the cervix, the poor physical health of patients with carcinoma of the endometrium must be considered more carefully. The patient with adenocarcinoma of the endometrium will be older, obese, often diabetic, and physically infirm with hypertensive cardiovascular disease. (5) If we find evidence that the radical hysterectomy should be used more often, what should be the treatment plan? Advise radical hysterectomy for all patients with adenocarcinoma of the endometrium, thus replacing the conservative hysterectomy as the standard operation, or identify patients individually? If the latter method is needed, then by what criteria do we choose those patients who need the radical hysterectomy? Since the present methods of treatment are so successful, benefits from the more radical operation must be assured by individual selection for the hazards of postoperative complications and deaths are going to be greater. DISCUSSION To return to these questions separately for further consideration: What can we expect of the radical hysterectomy which cannot be accomplished by the conservative hysterectomy? The scope of the radical hysterectomy may excise as much as 50% of the vagina measured by the Iength. This additional removal of the vagina will be therapeutic when adenocarcinoma arising within the corpus spreads down into the cervix and on to the vagina. If such an amount and distribution of carcinoma is to be treated surgically, clearly the extended scope of the radical hysterectomy will be necessary. Many gynecologic oncologists recognize that patients with stage II adenocarcinoma of the
RADICAL
HYSTERECTOMY
IN
ENDOMETRIAL
CANCER
333
endometrium are potentially candidates for an operation which removes more of the vagina. A radical hysterectomy also resects parametrium, and this may benefit patients with adenocarcinoma of the corpus involving the lower segment of the uterus, where there is a significant frequency of paracervix metastasis. Within the literature, the statement is repeated that “adenocarcinoma involving the cervix becomes accessible to the lower uterine vasculature and may metastasize laterally by way of the lymphatics serving the cervix. The treatment problem of stage II becomes more like that of cancer of the cervix. Thus, the treatment should be similar” [l-3]. We all recognize that the usefulness of radical hysterectomy for stage I and II carcinoma of the cervix and would be willing to use radical hysterectomy for stage II carcinoma of the endometrium if the spread patterns are indeed similar [4]. Although the use of radical hysterectomy for stage II endometrial carcinoma has good theoretical support, the direction and the schedule for metastasis is still unsettled and may not be sufficiently similar to carcinoma of the cervix for us to assume that an interchange of treatment would be equally effective [5]. Spread may be infrequent, and when present, too complex for surgical excision to make complete excision for all positive nodes feasible. Although the biological behavior of carcinoma of the endometrium favors the patient by a relative reluctance of the cancer to leave the corpus, still lymphatic metastases from the corpus disease stage I do develop [1,6,7]. Extension to the cervix is not necessary for lymphatic metastasis, While the overall incidence of metastasis from stage I adenocarcinoma of the endometrium is approximately 10% and this low incidence may not justify routinely removing the pelvic nodes, some patients may deserve lymphadenectomy. For example, an increased frequency of metastasis to the regional nodes has been demonstrated by some reports [8-111 if there is deep penetration of the uterine wall musculature by the carcinoma, and myometrial invasion occurs earlier when the histologic characteristics of the endometrial cancer are undifferentiated. We must also be reassured that lymphadenectomy will be curative. Since the lymphadenectomy phase of the radical hysterectomy is considered a major aspect of the procedure, we need to understand its potential for increasing the cure rates in those patients treated. Again, we may wish to transfer our knowledge of treating cancer of the cervix to this deliberation. The value of lymphadenectomy for curing node metastasis from carcinoma of the cervix is roughly 30%-50% but for adenocarcinoma of the corpus, the result is more disappointing for it drops from 25% to 30% [12,13]. Still a cure rate with positive nodes in one fourth to one third of the patients with adenocarcinoma of the endometrium is not insignificant, and is especially important to the fortunate individual who was cured by excising node metastasis, and in a small way, these additional cures contribute to the overall salvage of this cancer. These predictions for improvement depend upon a small operative mortality; otherwise, the success will be erased by another form of treatment failure. The question of whether radical hysterectomy can be applied safely and ef-
334
FELIX
RUTLEDGE
ficiently is of major concern. The adverse physical features and poor health of patients with carcinoma of the endometrium will disqualify many patients for radical hysterectomy. Obesity imposes more hazards for complications while the scope of the resection is compromised. Greater age and associated infirmities fail many patients after the postoperative evaluation. Thus, a large portion of those who most need additional radicality of therapy will be unsuitable for operation. Unless we can assure higher incidence of operability and a low primary mortality, the promise of markedly improved cure rates for all patients with adenocarcinoma of the endometrium by more frequent use of radical hysterectomy dims. For those patients who are a greater risk for metastasis and are physically suitable, there is the potential of benefit. Whether it is an attempt to apply radical hysterectomy as routinely as possible or on an individual basis may be decided by our ability to identify those patients who need more extended resection. To support the radical hysterectomy as a more standard therapy, there should be supporting evidence that spread to the upper vagina, parametrium, and regional nodes is a common cause for failure by the more standard conservative hysterectomy. What proportion of the disease in carcinoma of the endometrium is stage II and III. Certainly there should be a high incidence to justify a more radical resection.
Radical
Hysterectomy
for Corpus et Endocervicis
(stage II)
We should consider stage II first for extension to the cervix has the most popular support for radical hysterectomy and presents three sites for greater potential metastasis which would not be adequately included in the conservative hysterectomy. Frequent parametrial and upper vaginal and pelvic wall node metastasis makes the stage II patient a more likely candidate for the radical hysterectomy. The proportion of stage I and stage II disease varies surprisingly among different series of patients from 6% to 20% (Table I). This range of incidence figures may seem to reflect upon our ability to clinically stage the disease and could be used as an argument for wider resection of stage I disease to assure adequacy; however, several factors may influence the ratio of early to late stages among various series of patients reviewed. The population which comprises the series, the motivation of the patients to seek medical attention early, the economic means to obtain the diagnostic testing, and the medical program provided for them for early detection are factors which raise the proportion of stage I and lower the incidence of stage II and III. This range in frequency may be due to an inconsistent clinical staging. To suggest that this variation in the ratio to stage I to II could be due to different techniques for establishing the diagnosis is only speculative; however, the readiness with which the diagnosis is made depends upon the clinical evidence of spread to the cervix and the thoroughness with which a search is made. An accurate diagnosis for those patients who have a lesion on the cervix can be made by biopsy directed at the clinically apparent lesion. There are additional patients with stage II cancer of the endometrium for whom the cervix
RADICAL
HYSTERECTOMY
IN
ENDOMETRIAL
TABLE I ADENOCARCINOMA ENDOMETRIUM FREQUENCY OF CORFVS ET CERVICIS Author
Year
Roberts Gusberg Hawksworth Morris Carmichael Rickford Kotlmeier Lee Neilsen and Koller Sal1 et al. Moltz et al. Karlstedt Boronow (MDAH)” Davis Lewis et al. Frick MDAH
1961 1964 1964 1967 1967 1968 1969 1969 1969 1970 1972 1968 1969 1964 1970 1973 1973
a The
University
of Texas
System
Cancer
Number
CANCER
STAGE
II
of patients
% Stage
281223 40/518 271345 71265 58l693 9150 133/1123 14/150 1531634 10/307 81169 103/1165 631270 751525 221129 221348 1091737 Center
M. D. Anderson
335
13 8 8 3 10 18 11 9 24 3 5 9 23 14 17 6 15 Hospital
and Tumor
Institute.
appears grossly normal, and for these a routine biopsy of the portio of the cervix and a fractional curettage of the endocervical canal would detect the subclinical metastasis. If applied routinely, these tests are more likely to establish the true condition of the lower segment of the uterus; the reverse may be true if certain precautions are not practiced [2,5,8,14]. False positive specimens may be obtained by fractional curettage as contaminants by fragments of cancer from the corpus, or by a polyploid portion of the corpus cancer extending down into the endocervical canal. Although this is not likely to occur often, it would influence the frequency ratio of stage I to stage II. Whether curettage alone is accepted by the clinician as a single evidence of spread to the cervix or discounted would influence the incidence of stage II. The care by which the corpus is excluded before fractional curettage by inserting a gauze plug to the level of the internal OSmay lower the incidence of some series by eliminating false positive specimens. Likewise, the true condition of the cervix will be confirmed if the histologic specimen contains adenocarcinoma growing in relationship to the endocervical glands or endocervical stroma. When consideration is given to all these factors for establishing spread to the cervix, the portion of patients with early stage I still dominates. If we accept the occurrence incidence range of 15%-20% of the patients with endometrial cancer as having spread to the cervix, we see that the frequency alone would not justify routine radical hysterectomy for all patients with adenocarcinoma of the endometrium. Yet stage II may remain an indication for individualized treatment by radical hysterectomy in about one fifth of
336
FELIX
RUTLEDGE
the patients. We need not conclude that the different ratios from stage I to stage II among various series reported reflect seriously upon our ability to clinically identify spread to the cervix. Only a few patients with stage I prove to be more advanced by examination of the surgical specimen 1151. When care is taken to sample the cervix and lower uterine segment, there is consistency between the clinical appraisal and the findings at the time of operation and histologic study of the specimen. The role for radical hysterectomy and lymphadenectomy seems established for stage II patients where the frequency of metastasis beyond the uterus warrants treating all stage II patients as if the metastasis was established. Treatment by radical hysterectomy is most popular for stage II adenocarcinema of the endometrium, and with this stage, more information is available about 5 yr survivals and incidence of metastasis. Although the 5-yr cure rates for stage II treated by extended surgery range from some 20% to 50% among the reports reviewed, the success rate with radical hysterectomy generally is superior, Although we expect the modern irradiation therapy methods to show improvement with the new megavoltage equipment, the evidence is not yet conclusive. At present, the radical hysterectomy has a strong position in the treatment of stage II lesions, but much less secure in the treatment of stage I. The literature provides few statistics with the results of radical hysterectomy for stage I carcinoma of the endometrium. The preponderance of reports available are concerned with those patients treated by conservative hysterectomy and irradiation. In addition, from the material available, a comparative evaluation of radical hysterectomy is not possible in many instances because operability rates for the series using radical hysterectomy indicates much selectivity. There is some information provided about the cure rates obtainable by radical hysterectomy from series in which all patients are included. Radical
Hysterectomy
for Corpus
(Stage I)
Any superiority of radical hysterectomy over the conventional hysterectomy for stage I lesions would indicate that the patient did have metastasis removed by the more extended operation. We recognize a spread pattern from the corpus to the regional nodes without the necessity of the involvement of the cervix. Since the corpus lesion is adequately treated by conservative hysterectomy, to advise radical hysterectomy with associated lymphadenectomy for stage I expresses a concern for metastases to the regional nodes. The incidence of positive nodes for stage I adenocarcinoma of the endometrium averages about 10% (Table II). The higher incidence of figures ranging up to 24% for some series can usually be explained by selection of patients with a greater risk for positive nodes or by counting patients whose nodes were removed only because they were abnormal. It is apparent that the frequency of positive nodes for stage I carcinoma of the endometrium will not justify routine lymphadenectomy; however, lymphadenectomy may well be a useful treatment if by selectivity the patients with a greater risk for node metastasis can be identified, The incidence of me-
RADICAL
HYSTERECTOMY
IN TABLE
ENDOMETRIAL
337
CANCER
II
ENDOMETFUAL CARCINOMA FREQUENCY OF LYMPH NODE METASTASES Patients positive Author Randall Bmnschwig Liu and Meigs Lefevre Schwartz and Brunschwig Roberts Andersen and Stephens Barber et al. Davis Parsons Hawksworth Winterton Rickford Lees Morris Lewis Stallworthy
Year
No.
1950 1954 1955 1956 1957 1961 1961 1962 1964 1959 1964 1964 1968 1969 1967 1970 1973
4120 lOj57 11147 7145 13196 10/34 4152 12185 7156 4150 8164 8176 5150 13/76 4/21 17/129 18/131
with nodes % 20% 17% 23% 16% 14% 29% 8% 20% 12.5% 8% 12.5% 10% 10% 17% 20% 13.2% 14%
Stage Not
I
stated
Stage Not
II
stated
4133 12% Not stated
7114 50% Not stated
5122 23% Not stated
218 25% Not stated
Not
Not
stated
6/11 2136 3156 16 12/107
stated 18.7%
219
418 11.2%
5 5122 23% 11127 40%
tastasis to the regiona nodes is increased when the histologic pattern of the carcinoma is undifferentiated and penetration of the cancer into the uterine wall is deep [Z&16]. Under these conditions, the incidence of regional nodes is increased to a frequency that requires treatment either by lymphadenectomy or irradiation.
Results
(Findings)
Table III presents some example reports of treatment results employing varied methods. For some authors both the absolute and the corrected 5-yr survivals are presented. From the representative reports the inadequacies of current treatment of adenocarcinoma of the endometrium are evident and show that we should not be complacent, but instead, strive to better our treatment of this disease. The reports which give results of treatment of radical hysterectomy are presented in Table IV. The 5-yr survival statistics are generally superior. Since patients with adenocarcinoma of the endometrium are poor candidates for operation, the operability percentages shown in Table V are of practical interest. When selection is liberal, a larger percentage of the poor-risk patients and those with more advanced spread may be judged operable. One wonders about the number of operative deaths, and notes in Table VI that the primary mortality for radical hysterectomy is not significantly greater than those experienced in other reports employing conservative hysterectomies. This may suggest that, if a patient can tolerate laparotomy, her postoperative course may
338
FELIX
RUTLEDGE TABLE
TREATMENT
III
ADENOCARCINOMA ENDOMETRIUM 5-Yr
Author
survival
Year
No. Pts.
Absolute
Whetham Ingiulla Moltz et al. Bastiaanse Roberts Parsons Gusberg Hawksworth
1972 1968 1972 1952 1961 1959 1964 1964
257 22/112 169 2171264 223 62 2901518 167/243
58.3% 73.2% 72% 72.5% 1431223 (23/33) 78% 55.9% 69%
Anderson Carmichael Wade et al. Karlstedt Keller Lewis and Stallworthy
1964 1967 1967 1968 1969 1970
52 3981603 265 1123 4091634 252
83% 66% 67.5% 61% 64.6% 68.2%
Sal1 Stallworthy Frick Schlink
1970 1970 1973
307 131 348 3651465
68195 = 71.6% 66.1% 60%
a Corrected
= death
from
intercurrent
Corrected’
Year
Radical hysterectomy plus lymphadenectomy Schwartz and Brunschwig” 1957 Parsons 1959 Winterton 1959 Roberts 1961 Lees 1969 Rickford” 1968 Lewis 1970 Stallworthy 1970 Total hysterectomy plus lymphadenectomy Andersen and Stephens 1964 LefevreC 1956 Davis 1964 o Brunschwig advocated radical b Full Wertheim all patients. c Advocated radical hysterectomy.
hysterectomy
Vaginal
hysterectomy
60.4%
Radical hysterectomy lymphadenectomy 85% 72.6% 69% Radical hysterectomy, 129 patients, 71.5% 68% 73%
diseases
not counted.
TABLE
IV
ADENOCARCINOMA ENDOMETFUUM TREATMENT
Author
Vaginal
BY EXTENDED OPERATION
Absolute 5-yr survival
No. pt
37
129 131
2.8137 73% 78% 76% Not 63% Not 71.5% 68/95 71%
52 42 151
83% Not 68.5%
99 27 76
hysterectomy.
Corrected 5-yr survival
81.5% 84.0%
Selection
Selective (26%) Selective Consecutive
given Consecutive Consecutive Consecutive
given
85% given
Consecutive Consecutive Selective
+
RADICAL
HYSTERECTOMY
IN
ENDOMETRIAL
CANCER
339
TABLE V OPERABILITY Inguilla Andersen and Stephens Lees Bastiaanse Wade et al. Hawksworth Roberts Rutledge Winterton Rickford
5961573 52171 76/150 2521264 2451265 2211243 271223 5161737 89190 1521174
88.3% 74% 50% 96.2% 85.7% 91% 12% 70% 95% 87%
be as safe with radical hysterectomy and lymphadenectomy, or lymphadenectomy alone, as with conservative hysterectomy only. Perhaps our fears of the increased hazards of radical hysterectomy above those of the conservative hysterectomy are not founded in these experiences. Treatment
Results
(Stage ZZ)
The indication for radical hysterectomy in adenocarcinoma of the endometrium stage II seems better supported for several reasons already mentioned. The results are noted in Table VII. Just as the incidence of stage II ranges widely among authors, the presented survival also varies widely. The various degrees of advanced cancer and amounts of metastatic cancer may be the explanation. The rigidity by which the criteria for operability are applied and the preoperative search for metastases will influence treatment results. The TABLE VI COMPLICATIONS
Year
Size of series reported
Liu Meigs Brunschwig
1955 1957
57
Parsons
1959
62
Winterton Andersen and Stephens Roberts Davis Lees Lewis and Stallworthy Rutledge Ingiulla Rickford
1959 1961 1961 1964 1969
Author
a Op.
mort.
= postoperative
1973 1968 1968 mortality.
99 52 27 56 R.H. 76 R.H. 129 5231737 5031573 50
+ La.
Complications l/60 op. mart.” 1.6% Fistulas (6/57) 11%; op. mort. 2196 = 2.2% Fistulas (S/60) 8%; atony and incontinence 12%; 27% postop. complications Op. mort. 3/99; one fistula No op. mort.; no fistulas Op. mort. 2/27 = 7%; no fistulas Op. mort. l/2%; 1.5% fistulas Op. mort. 2/76; 2.6% pul. emb. Op. mort. 3/129 = 2.3% Op. mort. 1 = 3% Op. mort. 2% Not given
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TABLE VII ADENOCARCINOMA ENDOMETRIUM SURVIVAL CORPUS ET CERVICIS (STAGE II) Author
Year
Schwartz and Brunschwig Roberts Gusberg Hawksworth Davis Wade et al. Kottmeiei Neilsen and Koller Sal1 Moltz et al. Kalstedt Boronow Lewis et al. Frick
1957 1961 1964 1964 1964 1967 1969 1969 1970 1972 1968 1969 1970 1973
a Kottmeier
No. pt. surviving 12137 19128 11/40 5117 19/81 7 581133 4/153 5/10
318 451103 63 13122 8122
% Survivals 42% 68% 27.5% 29% 24% 9.4% 44% 26% 50% 38% 44% 60% 60% 36.4%
corrected = 51%
series which depends upon clinical examination to identify metastasis will generally have more advanced cancers in the stage II category. More curable patients in stage II will be diagnosed before treatment only when a search for the subclinical metastasis by cervical biopsy and fractional curettage is a routine practice. Whether the report represents clinical or surgical staging becomes important. The differences in clinical staging (FIGO) and the clinicopathological (clinical staging altered by findings at laparotomy and pathological study of the specimen) could explain some reports with unusually good outcome. More accurate interpretations and conclusions of reports would be helped if a single method for staging was employed or if results of both clinical (FIGO) and clinicopathological staging were supplied by the author. Generally, the accomplishments for radical hysterectomy as a treatment for endometrial carcinoma are commendable and help secure a role for this method of treatment.
Treatment
Results
(Stage I)
The results of the management of stage I patients by radical hysterectomy have been successful in diminishing the incidence of vaginal recurrence, but the results with conservative hysterectomy and preoperative irradiation of the upper vagina have been equally successful and more easily accomplished. Most will agree that this is not a strong argument for employing radical hysterectomy in stage I disease and will agree that preoperative irradiation will sterilize subclinical metastasis about the upper vagina preventing local recurrences after conservative hysterectomy for adenocarcinoma of the endometrium. Fewer clinicians are convinced that the external therapy will accomplish the same for nodal metastasis; therefore, the dominant remaining need for extending operation in stage I is lymphadenectomy. Control of the
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cancer which has metastasized to the pelvic nodes by operation also has skeptics. A sampling of the reports for the past 25 yr shows that the pelvic lymphadenectomy has not been popular; although several centers have some experience, even the largest of the series represents fewer than 100 patients. This becomes especially significant when the total number of patients treated by these same authors numbers into several hundreds. The curability of positive nodes may be noted in Table VIII to range from 15% to 35%.
Complications
of Treatment
The radical hysterectomy introduces the risk of postoperative urinary tract complications. It increases the dangers of hemorrhage and infection after hysterectomy and because the duration of the operation and recovery are lengthened, the complications of the cardiovascular and respiratory systems must be more frequent. Yet the tolerance as indicated by Table VI seems acceptable. The first listing in the table represents the complications of radical hysterectomy; next are those of total hysterectomy and lymphadenectomy; and lastly, those of conservative hysterectomy alone. These statistics would suggest that with properly chosen patients and expertly performed surgery the radical hysterectomy can be employed safely.
Conclusions
Excerpted
from the Literature
Lees (1969, Sheffield, England) reported 14 yr of his experience performing radical hysterectomy consecutively on 150 patients. This represents all the patients seen in all stages. Although he was dedicated to applying this operation consecutively, only 76 of 150 had the radical hysterectomy and lymphadenectomy. Lees concluded: “The evidence from this consecutive and unselected group indicates that the true incidence of positive nodes is at least 20 per cent. All the evidence indicates that surgery should be the primary treatment and that it must be radical to prevent recurrences.” Lees believed that “an extended radical hysterectomy and hemi-vaginectomy is the best procedure, that to attempt the Wertheim hysterectomy is a mistake. Lymphadenectomy gave no improvement in results in this series and the prognosis in gland positive cases was poor. Postoperative X-ray therapy TABLE
ADENOCARCINOMA ENDOMETRIUM Schwartz and Brunschwig Javert Parsons Lees Andersen and Stephens Barber Wade et al. Dobbie et al. Boronow Lewis et al. Total
1957 1952 1959 1969 1961 1962 1967 1965 1964
1970
VIII
SURVIVAL OF PATIENTS WITH POSITIVE NODES 2112 17% 5 yr 4114 28% 3-l/2 yr 214 2 yr; l/4 3 yr l/9 5 yr l/4 25% 5 yr 14/17 dead; l/17 lost; O/4 5 yr 417 5 yr O/S 5 yr 4111 5 yr 13168 20% 5 yr
l/17
5 yr;
l/17
10 mo
342
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has been adopted to replace the lymphadenectomy; however, note is made of suspicious node groups to aid the radiotherapists in directing the treatment.” Roberts (1961, Chelsea Hospital, London) reported a series of 27 patients who had radical hysterectomy for special indications selected from 223 patients admitted. The majority were treated with preoperative radium plus conservative hysterectomy as the standard treatment. “From the preceding results the operation of choice , . . (after preoperative intracavitary radium) . . . would appear to be total hysterectomy and bilateral salpingo-oophorectomy but if the operative scope is to be widened then there are reasonable grounds for performing Wertheim hysterectomy. This is especially true if there are grounds for suspecting that the cervix is involved.” Parsons (1959, Boston) concluded that the end results in this study compare favorably to those reported in the current literature and justifies further evaluation of the radical surgical approach for the treatment of endometrial carcinoma. “. . . it is hoped that future experience and observation . . . will improve the selection of patients and reduce mortality, at which time the Wertheim hysterectomy and lymphadenectomy may prove worthy of more routine use.” “Mention must be made of the discouragingly high rate of urinary tract complications. This problem, which has been difficult to solve, has precluded routine use of adequate radical surgery in the elderly, poor risk patient with endometrial carcinoma.” Lewis and Stallworthy (1970, Oxford, England): “Granted that the pelvic glands are involved in between 1 in 5 and 1 in 10 women, it would seem quite unnecessary to perform extended surgery on the majority of patients.” “The practical problem, therefore, is to find a way of selecting those patients at maximum risk of nodal spread and to plan the treatment most likely to be effective for the whole field at risk.” I‘ . . * surgical excision of the lymphatic nodes plus postoperative irradiation has had a favorable influence on prognosis.” Gusberg (1962) stated: “The rate of cure will be meager in those in whom nodes are positive. Nonetheless the wide dissection encouraged by the radical operation should permit an operative coverage of the lymphatics but not otherwise possible.” Gusberg recognized a role for extended operation in the treatment of adenocarcinoma, and the frequency with which it is prescribed should be decided for each patient. He plans for individualization of treatment by selecting the most effective methods for the therapeutic problems. From Stallworthy’s consecutive series of 136 patients, he arrived at four practical points of clinical interest, and these serve as an indicator that the field at risk of patients with adenocarcinoma of the endometrium increases with the stage of the disease. In the series, stage II, spread to the cervix occurs in 10% of the patients; positive nodes occur in 14% of all stages; the adnexae are involved in 5%; and in the vagina, 2%. This report provides information not previously available; thus, this article is recommended for detailed study.
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TABLE IX THE M. D. ANDERSON HOSPITAL AND TUMOR INSTITUTE CONSERVATIVE HYSTERECTOMY AND LYMPHADENECTOMY [103 Patients with Stage I (71), 11 (24), III (8)] Nodes negative Nodes positive Positive pelvic only Positive aortic only
97/103 6/103 4/103 21103
= = = =
94% 6% 4% 2%
a No survivals of patients with positive nodes.
Perhaps Professor Stallworthy has acquired a depth of clinical judgment while treating this series of patients which would satisfy our questions about this topic. Stallworthy’s conclusions are: Radical hysterectomy is advised for all patients with stage II lesions. For stage I patients with a well differentiated histology, the operation of choice is conservative hysterectomy; however, lymphadenectomy will be performed if the uterine specimen demonstrates deep myometrial penetration. If in stage I the tumor is poorly differentiated, a Wertheim hysterectomy and lymphadenectomy is performed as the treatment of choice. Patients who are found to have positive nodes receive postoperative X-ray therapy. Stallworthy showed that radical hysterectomy can be applied to a higher percentage of the patients with endometrial carcinoma in both stage I and stage II disease with 131 patients treated consecutively by Wertheim operation with lymphadenectomy. A 14% positive node incidence was encountered for the total series. There were 27 patients with stage II disease, yielding a 41% positive node recovery. The results are excellent for treating stage II lesions -a 5-yr cure rate of 59%. Stallworthy suggested that the treatment for stage II adenocarcinoma of the endometrium may be promptly decided in favor of the intracavitary radium and Wertheim hysterectomy with lymphadenectomy. For stage I lesions, however, the low incidence of metastases for the well-differentiated tumor makes it possible to treat these patients by conservative hysterectomy. When the histologic pattern is undifferentiated, the Wertheim hysterectomy and lymphadenectomy is advocated. We at the M. D. Anderson Hospital have not consistently practiced radical hysterectomy for either stage I or stage II lesions, preferring irradiation therapy and a conservative hysterectomy. An occasional patient has required radical hysterectomy when the anatomy was not suitable for intracavitary radium application. We have had some experience with conservative hysterectomy and lymphadenectomy (Tables IX and X). The development after lymphadenectomy of pelvic wall lymphocysts and added posttreatment fibrosis were the most frequent postoperative complications. These events which threatened ureteral obstruction and chronic leg edema diminished enthusiasm for the procedure, especially after no patients with node metastasis were cured. In addition, the lymphadenectomy prolonged the operation and recovery, conditions undesirable for this group of patients who were less suited physically for surgery.
344
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X
ADENOCARCINOMA ENDOMETRIUM THE M. D. ANDERSON HOSPITAL TREATMENT Stage IA IA IB II III-IV Postop. Depth muscle
Grade
Treatment
I II-III -
Hysterectomy Radium + hysterectomy W.P.a + radium + hysterectomy W.P. + radium + hysterectomy W.P. + radium
invasion ~5% Thickness > 50% Thickness
a Whole-pelvis
Vaginal radium W.P. + vaginal
radium
irradiation.
CONCLUSIONS About 1950 the radical hysterectomy had a surge of new popularity for carcinoma of the cervix, and shortly after this greater use of the radical hysterectomy and lymphadenectomy for endometrial carcinoma was suggested [17]. For several reasons, the more routine use of the radical hysterectomy did not prove feasible. Although the operation is eminently suitable for patients with certain conditions of endometrial carcinoma, the combination of conservative hysterectomy and irradiation found a greater usefulness for the majority. There is no evidence to warrant changing these conditions because: 1. Irradiation methods have improved for dosage and distribution, and when added to conservative hysterectomy, the range is expanded to equal the radical hysterectomy. 2. The high cure rate presently being obtained by conservative hysterectomy indicates that most patients do not need the more hazardous radical hysterectomy. 3. The older-aged patients with associated diseases limit the applicability of radical hysterectomy, often for the patient who needs surgical resection most. 4. Direct pathways to aortic nodes limit effectiveness of eliminating lymph node metastases by lymphadenectomy. A canvass of the reports available in the literature for analysis in whichconsecutive patients were treated with radical hysterectomy provides a very limited basis for assessing the effectiveness of this treatment. Because the number of patients is small, and selectivity makes judgment of the outcome difficult and what happened to the rest of the series is often not provided. Some additional information on the subject can be found among reports in which radical hysterectomy is employed selectively among some patients while the majority are treated with the more conservative hysterectomy. From both sources of information, an answer to several questions about radical hysterectomy to provide a wider resection for adenocarcinoma of the endome-
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trium can be obtained. Considering only surgical treatment, the conservative hysterectomy is still adequate for the majority of patients’ needs. The percentage of clinical stage I disease in most series is usually more than two thirds the total number. The relative accuracy of the clinical staging is confirmed because removal of the uterus alone will produce a S-yr survival of 80%. Still better survival may be possible, for some stage I patients die because metastases are not included in the treatment. Inability to exclude metastases before treatment prevents a positive statement that none of the patients with stage I would need radical hysterectomy or lymphadenectomy. If we propose to employ extended hysterectomy more liberally, then we must make a decision as to whether to apply it as a routine procedure or selectively on the basis of individual needs. Beecham [ 181 has suggested that radical hysterectomy should be applied routinely and that the disease, adenocarcinema of the endometrium, will benefit if all the patients with the more favorable lesions are treated more radically. Another opinion [8,16] suggests that the radical hysterectomy be prescribed on a more individual basis noting that the incidence of positive nodes in stage I is quite infrequent when the tumor is well differentiated and without muscular wall invasion. These patients with the more favorable lesions will not benefit, and they would be sub jetted unnecessarily to the hazards of the more extended operation. This more conservative approach is supported by the high curability rates of stage I lesions. Still a third philosophy of treatment of adenocarcinoma of the endometrium as practiced by the staff at The University of Texas System Cancer Center M. D. Anderson Hospital employs irradiation to expand the range of the therapy beyond that capable of conservative hysterectomy. To support this plan, one must be confident in the effectiveness of irradiation therapy to destroy metastatic sites of adenocarcinoma both in the parametrium and the upper vagina and pelvic wall nodes (Tables X and XI). There is no reason to doubt that irradiation will sterilize a metastasis which is small. The characteristics of the disease which may indicate the need for a radical hysterectomy and lymphadenectomy are also indicators for a wider range of treatment by irradiation provided by external therapy. For example, patients with an enTABLE
XI
ADENOCARCINOMA ENDOMETRIUM THE M. D. ANDERSON HOSPITAL 1948-1969 RESULTS OF TREATMENT 5-yr Clinical
Total
stage
I II III IV Total u Includes
cases 516 118 70 33 737
death
from
all causes.
survival”
No.
%
367 52 13 1 433
71.1 44.0 17.0 3.0 58.8
346
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RUTLEDGE
larged uterus and a microscopic pattern of undifferentiated tumor are a signal for intensive preoperative external therapy combined with intracavitary radium. A diminished dose is, of course, necessary because the external therapy contributes to the limits of tolerance. Those patients with stage II adenocarcinema of the endometrium with the clear need for more extended treatment of the primary and pelvic wall nodes should receive more extensive preoperative X-ray therapy followed by conservative hysterectomy. It is not suggested that the more intensive preoperative irradiation therapy be combined with radical hysterectomy, for in our experience such a plan induces intolerable complications. Although we suggest that external therapy will accomplish the same as extended surgical resection, still there is a role for radical hysterectomy in this scheme. For patients who present conditions which conflict with the use of external therapy or have an anatomical problem which is expected to hamper the effectiveness of irradiation therapy, it would seem logical to advocate radical hysterectomy. REFERENCES 1. ROBERTS, D. W. T., Carcinoma of the body of the uterus at Chelsea Hospital for Women, 1943-1953, J. Obstet. Gynaecol. Brit. Commonw. 68,132-138 (1961). 2. PARSONS, L., AND CESARE, F., Wertheim hysterectomy in the treatment of endometrial carcinoma, Surg. Gynecol. Obstet. 108,582-590 (1959). 3. LEFEVRE, H., Node dissection in cancer of the endometrium, Surg. Gynecol. Obstet. 102, 649-656
(1956).
4. SALL, S., SONNENBLICK, B., AND STONE, M. L., Factors affecting survival ofpatients with endometrial carcinoma, Amer. J. Obstet. Gynecol. 107, 116-123 (1970). 5. WINTERTON, W. R., Discussion on carcinoma of the body of the uterus, Proc. Boy. Sot. Med. 47,897-899 (1954). 6. RICKFORD, R. B. K., Involvement of pelvic lymph nodes in carcinoma of the endometrium, 1. Obstet. Gynaecol. Brit. Commonw. 75,580 (1968). 7. LEES, D. H., An evaluation of the treatment of carcinoma of the body of the uterus. J. Obstet. Gynaecol. Brit. Commonw. 76,615-623 (1969). 8. STALLWORTHY, J. A., Surgeru of endometrial cancer in the Bonney tradition, Ann. Roy. Coil. Surg. Engl. 48,293-305 (1971). 9. JAVERT, C. T., Spread of benign and malignant endometrium in lymphatic system with note on coexisting vascular involvement, Amer. J. Obstet. Gynecol. 64, 780-802 (1952). 10. SCHWARTZ, A. E., AND BRUNSCHWIG, A., Radical panhysterectomy and pelvic node excision for carcinoma of the corpus uteri, Surg. Gynecol. Obstet. 105,675-680 (1957). 11. LIU, W., AND MEIGS, J. V., Radical hysterectomy and pelvic lymphadenectomy, Amer. J. Obstet. Gynecol. 69, 1-32 (1955). 12. LEWIS, B. V., STALLWORTHY, J. A., AND COWDELL, R., Adenocarcinoma of the body of the uterus, J. Obstet. Gynaecol. Brit. Commonw. 77,343-348 (1970). 13. DOBBIE, B. M. W., TAYLOR, C. W., AND WATERHOUSE, J. A. H., A study of carcinoma of the endometrium, J. Obstet. Gynaecol. Brit. Commonw. 72,659-673 (1965). 14. BORONOW, R. C., Carcinoma of the corpus: treatment at M. D. Anderson Hospital, in Cancer of the uterus and ovary, Year Book Publ., Chicago, pp. 35-61 (1969). 15. FRICK, H. C., MUNNELL, E. W., RICHART, R. M., BERGER, A. P., AND LAWRY, M. F., Carcinoma of the endometrium, Amer. 1. Obstet. Gynecol. 115,663-675 (1973). 16. GUSBERG, S. B., AND JONES, H. C., Selection of treatment for corpus cancer, Amer. J. Obstet. Gynecol. 80,374-379 (1960). 17. RANDALL, C. L., Letter to the editor: Panhysterectomy for uterine carcinoma, Amer.J. Obstet. Gynecol. 59,942 (1950).
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18. BEECHAM, C. T., Discussion of FRICK, H. C., MUNNELL, E. W., RICHART, R. M., BERGER, A. P., and Lawry, M. F. Carcinoma of the endometrium, Amer. J. Obstet. Gynecol. 115, 674 (1973). 19. ANDERSEN, J. L. C., AND STEPHENS, S. R., Survival in carcinoma of the endometrium following pelvic node dissection, Dan. Med. BUZZ. 11, 160-164 (1964). 20. BARBER, K. W., JR., DOCKERTY, M. B., AND PRATT, J. H., A clinicopathologic study of surgically treated carcinoma of the endometrium with nodal metastasis, Surg. Obstet. Gynecol. 115,568-573 (1962). 21. CARMICHAEL, J. A., AND BEAN, H. A., Carcinoma of the endometrium in Saskatchewan, Amer. J. Obstet. Gynecol. 97,294-307 (1967). 22. DAVIS, E. W., JR., Carcinoma of the corpus uteri, Amer. J. Obstet. Gynecol. 88, 163-170 (1964). 23. DELCLOS, L., AND FLETCHER, G. H., Malignant tumors of the endometrium: evaluation of some aspects of radiotherapy, in Cancer of the uterus and ouay, Year Book Publ., Chicago, pp. 62-72 (1969). 24. DEMUELENAERE, G. F. G. O., The case against Wertbeim’s hysterectomy in endometrial carcinoma, J. Obstet. Gynaecol. Brit. Commonw. 80,728-734 (1973). 25. FLETCHER, G. H., RUTLEDGE, F. N., AND DELCLOS, L., Adenocarcinoma of the uterus, Front. radiat. ther. oncol., Vol. 5, S. Karger AG, Basel, pp. 262-275 (1970). 26. GUSBERG, S. B., AND YANNOPOULOUS, D., Therapeutic decisions in corpus cancer, Amer. J. Obstet. Gynecol. 88,157-162 (1964). 27. HAWKSWORTH, W., The treatment of carcinoma of the body of tbe uterus, Proc. Roy. Sot. Med. 57,467-471 (1964). 28. INGIULLA, W., AND COSMI, E. V., Vaginal hysterectomy for the treatment of cancer of the corpus uteri, Amer. J. Obstet. Gynecol. 100,541-543 (1968). 29. KARLSTEDT, K., Carcinoma of the uterine cervix, factors bearing on the curability, Acta Radial. Suppl. 282 (1968). 30. KOTTMEIER, H. L., Carcinoma of the corpus uteri: diagnosis and therapy, Amer. J. Obstet. Gynecol. 78,1127-1140 (1959). 31. KOTTMEIER, H. L., Individualization of therapy in carcinoma of the corpus, in Cancer of the uterus and ouay, Year Book Publ., Chicago, pp. 102-108 (1969). 32. MOLTZ, A., POMERANCE, W., AND STREISFELD, S., Adenocarcinoma endometrium, Obstet. Gynecol. 39, 199-201 (1972). 33. MORROW, C. P., DISALA, P. J., AND TOWNSEND, D. E., Current management of endometrial carcinoma, Obstet. Gynecol. 42,399-406 (1973). 34. NG, A. B. P., AND REAGAN, J. W., Incidence and prognosis of endometrial carcinoma by histologic grade and extent, Obstet. Gynecol. 35,437-443 (1970). 35. NILSEN, P. A., AND KOLLER, O., Carcinoma of the endometrium in Norway 1957-1960 with special reference to treatient results, Amer. J. Obstet. Gynecol. 105, 1099-1109 (1969). 36. SCHLINK, H., Cancer of the female pelvis, J. Obstet. Gynecol. Brit. Commonw. 67,402410 (1960). 37. ULFELDER, H., Advances in therapy of carcinoma of the uterine body and cervix, Acad. Med. N. J. BUZZ.8,201-206 (1962). 38. VAN BOUWDIJK BASTIAANSE, M. A., Cancer of body of uterus, J. Obstet. GynecoZ. BTit. Commonw. 59,611-616 (1952). 39. WADE, M. E., KOHORN, E. I., AND MORRIS, J. McL., Adenocarcinoma of the endometrium, Amer. J. Obstet. Gynecol. 99,869-876 (1967). 40. WHETHAM, J. C. G., Carcinoma of the endometrium, Amer. 1. Obstet. Gynecol. 112,339-343 (1972).