Recent Advances in the Surgical Treatment of Primary and Recurrent Cancer of the Uterus

Recent Advances in th(( Surgical Treatment of ~rimary and Recurrent Cancer of the Uterus

,

MICHAEL NEWTON, M.D., F.A.C.S., F.A.C.O.G. .

ProfeJJsur and Chairrrw,n, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine; Obstetri~an and Gynecologist-in-Chief, University of Mississippi Hospital, Jackson

CANCER oF THE UTERUS accounts for the majority of cases of malignant disease of the female genital tract. Several general points applicable to both types, cancer of the cervix and of the fundus uteri, are worth enumeration. First, it is essential to make as exact a diagnosis as possible before beginning treatment. Screening methods such as cytologic studies have recently become available and should b~ fulljr'utilized. However, it is important not to rely solely on these but to obtain a tissue diagnosis in every case. Second, although surgical treatment is an important part of management, radiation is often equally or more effective, while chemotherapy may have an increasing part to play. It is . essential that the surgeon consult with physicians who are well versed in these fields before treatment is decided for the individual patient. Third, recent advances in ancillary services have made possible more radical approaches to excision of the pelvic viscera. However, these procedures must not be undertaken lightly. They should be performed only upon specific indications and with full knowledge of all the difficulties likely to be encountered.

CANCER OF THE CERVIX UTERI

It is essential to determine the extent of the disease before finally deciding upon the exact therapy. Specifically, this involves the full use of all available diagnostic methods, including adequate pelvic examination, colposcopy, spot biopsy and cold-knife conization. 28 Once the diagnosis of intraepithelial disease has been established and invasive cancer excluded, treatment can be begun as outlined below. If,

531

532

MICHAEL NEWTON

Table 1.

Carcinoma of Cervix-Pretreatment Work-up

1. General History and Physical Examination 2. Hematology-Complete blood count, coagulogram 3. Blood Chemistry-Serology, blood urea nitrogen, fasting blood sugar, total serum proteins with albumin/globulin ratio 4. Urinary Tract-Urinalysis (clean-catch specimen), urine culture (if indicated), intravenous pyelogram, cystoscopy 5. Intestinal Tract-Proctoscopy, barium enema 6. Miscellaneous-Chest x-ray, electrocardiogram

however, invasive cancer is found, further work-up and evaluation are essential both to exclude local and distant spread of the disease and to serve as a baseline for future investigations durfug and after treatment. The scope of this study will be guided by the individual case but the minimum is indicated in Table 1. Following appropriate work-up a complete evaluation of the patient should be made. This is best done by those who will be concerned with her treatment (usually the gynecologist and the radiologist). It should cover the pathological diagnosis, the general physical and emotional Table 2.

Carcinoma of Cervix-Clinical Staging*

Intraepithelial, preinvasive, in-situ carcinoma t The carcinoma is confined to the cervix M. Microcarcinomat A. Carcinoma less than 1 em. in diameter B. Carcinoma more than 1 em. in diameter STAGE II. The carcinoma involves the vagina but not the lower third. The carcinoma infiltrates the parametrium but has not reached the pelvic wall. The carcinoma extends to the corpus. A. Carcinoma encroaching upon the vaginal wall or involving the corpus but not obviously infiltrating the parametrium B. Carcinoma infiltrating the parametrium STAGE III. The carcinoma involves the lower third of the vagina. The carcinomatous infiltration of the parametrium has extended into the pelvic wall when on rectal examination the infiltration feels firm and nodular and there is no smooth cancer free space between the tumor and the pelvic wall. A swelling on the pelvic wall, not attached to the tumor, should not be considered in the staging. STAGE IV. The carcinoma involves the bladder or rectum, or has extended outside the true pelvis, i.e., below the vaginal inlet or above the pelvic brim (distant metastasis). A. Clinical invasion of the bladder or rectum B. Histologically proved invasion of the bladder or rectum, ulceration, or fistulas; extension of the carcinoma outside the true pelvis STAGE V. Carcinoma inadequately treated or recurrent after treatment A. Carcinoma inadequately treated B. Carcinoma recurrent after adequate treatment

STAGE 0. STAGE I.

*Adopted from M. Newton and K. A. Bolten.28 t Borderline or questionable invasion is regarded as intraepithelial carcinoma. t Microcarcinoma is diagnosed when invasion of less than 5 mm. though the basement membrane is seen in one area only on semiserial sections from a cone specimen.

Primary and Recurrent Cancer of the Uterus

533

condition of the patient and a determination of the extent of the cancer. At present the last is best done by "clinical staging" as a result of vaginal and rectal examinations. An international classification has been in use for some years and has been widely accepted as a crude but useful guide to treatment and prognosis. It was expanded and modified by Blaildey et al.2 and we have adopted this modification with minor changes (Table 2). Although many classifications have been suggested and are of value, it is best to use one that is well known so that results may be compared from clinic to clinic. Treatment

INTRAEPITHELIAL CARCINOMA. Definitive treatment of intraepithelial carcinoma consists of a total hysterectomy. The procedure may be done abdominally or vaginally. Because of the possibility of multicentric origin, a 1 to 2 em. length of vaginal cuff should be removed. The ovaries may be safely preserved. In 361 cases where the diagnosis was clearly established Parker et al. 32 found this treatment to be virtually 100 per cent effective. There is no need to perform a radical hysterectomy or to remove the pelvic lymph nodes. By the same token, full radiation is not indicated: the effect of lesser amounts of radiation upon tumor cells is uncertain. In the younger woman who is anxious to have children, it is desirable to avoid hysterectomy. Studies by Parker et al. 32 and by Krieger and McCormack20 have shown that wide conization can usually be safely performed in these patients. Careful follow-up at regular intervals is essential with repeated cytologic studies and further biopsies as indicated. A suggested program is that the patient be seen every three months for the first year, every six months for the second year and yearly thereafter. Although cytologic atypicalities may occasionally follow, the danger of the development of invasive cancer is slight, provided that the patient is seen regularly. Individualization is important, however, since, if the intraepithelial changes are very extensive, complete removal may not be possible by conization. After a woman who has received this conservative treatment has had the family she desires, there is no indication for hysterectomy, unless there is current evidence of disease. When intraepithelial carcinoma is diagnosed during pregnancy-and the same diagnostic methods apply whether the patient is pregnant or not~the patient should generally be allowed to proceed to term and delivery performed by the vaginal route. Later, at the six-weeks' checkup, further studies should be performed and appropriate treatment advised. INVASIVE CARCINOMA. The present status of primary surgical management of invasive carcinoma of the cervix is hard to evaluate. During the years 1920 to 1940 radiation had virtually replaced surgical treat:..

534

MICHAEL NEWTON

ment in the United States and, indeed, still remains the therapy most commonly used here. In other countries, however, the surgical approach was continued in some areas and during the last 15 years there has been a resurgence of interest in it in the United States. As a result, many different techniques of surgical therapy, both alone and in combination with radiation, are used today. 1. Radical Abdominal Hysterectomy. This procedure has been used most often for early invasive cancer-Stages I, IIA and possibly liBand rarely for more advanced disease, because of the difficulty of circumventing the tumor. Recent reports indicate five-year survival rates of 70 to 80 per cent in Stage I and 50 to 60 per cent in Stage II. These figures compare favorably with those for radiation therapy, but in most instances the patients are selected to some degree. The operative procedure most frequently used is derived from that described by Meigs. 25 Emphasis .is placed on dissection of the pelvic nodes from the bifurcation of the aorta down to the inguinal ligament, wide removal of the parametrial and paravaginal tissue with exposure of the lower ureter and ureterovesical junction, and excision of the upper one-third to one-half of the vagina. The ovaries are generally removed, but, in the younger woman, the necessity of this has been questioned by McCall et al. 24 Of the variations in technique which have been suggested, the posterior approach of Yagi40 is of particular interest. Preoperative preparation is important, especially the replacement of blood volume. During operation good anesthetic management is essential and sufficient blood must be available for replacement since the loss may occasionally be large and sudden. Radical hysterectomy should have a low (1 to 2 per cent) operative mortality. However, there are certain recognized complications. These include (1) fistula formation, (2) temporary loss of bladder function, (3) pelvic hematoma and (4) shortening of the vagina. Ureterovaginal, vesicovaginal and rectovaginal fistulas occur in that order of frequency in perhaps 5 to 10 per cent of cases. The ureterovaginal fistula is the most serious, and attempts to prevent its development have included avoiding excessive denudation of the lower ureter and transposition of the ureter within the peritoneal cavity. 31 Bladder dysfunction is common if the operation has been sufficiently radical. Our preference is to leave the indwelling catheter in the bladder for at least seven days and then depend upon cystometrograms to indicate removal by showing whether the patient has return of sensation and motor power. Function usually returns, although it may not be entirely normal for some time. Pelvic hematoma can be minimized by careful hemostasis and occasionally by packing the pelvis at operation, but lymphoceles may sometimes present a problem. There is no .way to avoid shortening the vagina, but it is essential that the patient and her husband be informed of this possibility before operation.

Primary and Recurrent Cancer of the Uterus

535

2. Radical Vaginal Hysterectomy. This operation has been more popular in Europe than in this country, although interest in it has recently been shown here by Brunschwig4 and McCall. 23 In the hands of the skilled and experienced operator an adequate amount of vagina can be removed and a wide parametrial dissection performed, both of which compare well with those obtained by the abdominal route. This procedure may be less traumatic for the poor-risk patient and may carry slightly less risk of injuring the ureter. However, it suffers from two major disadvantages-(!) the abdomen cannot be explored fully and (2) removal of the pelvic nodes is less satisfactory since it must be a separate procedure and cannot be performed in continuity. It is possible that radical vaginal hysterectomy may have a place in the management of microinvasive carcinoma where the chance of lymph node metastases is low. 3. Combined Vagina-Abdominal Approach. This technique has been suggested in order to combine the advantages of the vaginal dissection with radical abdominal removal of the uterus and pelvic lymph nodes. 1 • 14 • 37 Laparotomy is usually performed first to determine the extent of the disease. This incision is then covered, and, with the patient in the lithotomy position, the vagina is divided and closed, the rectum and bladder separated and the tissue lateral to the vagina clamped, divided and ligated. The legs are then put down and the remainder of the operation completed from above. In our experience dissection deep in the pelvis has been facilitated by this technique, but the total operating time and blood loss have been slightly increased. 4. Combined Radiation and Surgery. Many different techniques have been described, and there has been insufficient time to evaluate them completely. The commonest method is to give either partial or complete radiation and follow this by a hysterectomy which may be radical, modified radical or even simple in type. Results reported so far show fiveyear survivals comparable to those obtained by adequate radiation or radical surgery. 13 • 36 • 38 The advantages of this approach may be an increase in survival rate for patients with Stages II and III lesions. 11 Possible disadvantages are an increase in complications, particularly in fistula formation, since radiated tissue may not withstand surgical trauma so well. The use of radiation following radical surgery has also been reported. 16 The best use of this technique would appear to be when surgical excision was thought to have been incomplete. A special facet of combined therapy has been the use of pelvic lymphadenectomy in association with full radiation therapy. Gorton 9 felt that this additional procedure improved survival rate over a short-term follow-up in patients with Stage I or II lesions. Continued interest in this technique has been reported by Claiborne et al.,7 Gray et al./ 0 and Rutledge and Fletcher36 because of the fact that radiation may not destroy tumor in pelvic lymph nodes. However, .the questionable im-

536

MICHAEL NEWTON

provement in survival rates and the postoperative complications make its value doubtful. It is apparent that further follow-up and more extensive studies are needed before the full value of each of the above methods can be assessed. Present knowledge indicates that in patients with Stages liB, III and IV lesions, radiation should to a large extent be the preferred therapy. However, in Stage I and possibly Stage IIA lesions, adequate radical surgery performed by an experienced operator may be better for the patient than poor radiation therapy. Conversely, good radiation therapy is far better than inadequate and blundering surgery. Where effective therapy in both fields is available, the preference of the physician in charge of the patient and the individual circumstances are important in deciding which to use. CARCINOMA OF THE CERVICAL STUMP. Since the operation of total hysterectomy is gradually superseding that of subtotal hysterectomy, carcinoma of the cervical stump should be found less frequently. Because of the long natural history of this disease, it is always difficult to be certain whether the stump carcinoma existed before the subtotal hysterectomy, especially if it is found within two years of operation. Whenever a cervix is left in place after a hysterectomy it should be studied adequately before the patient is discharged from hospital and she should be reminded to attend regularly for follow-up examinations. The principies of diagnosis and evaluation in stump carcinoma are similar to those described above for the whole cervix. Surgical treatment can be used for early lesions (Stages I and IIA) but presents some difficulty because of the lack of the fundus for traction and the proximity of the bladder to the cervical stump. However, excellent results can be obtained in selected early cases by radical operation. 8 ADENOCARCINOMA OF THE CERVIX UTERI. This and1.the adenaacanthoma (containing both adenomatous and squamous elements) account for about 5 per cent of cancers of the cervix. In a series of 46 patients with adenocarcinoma, Tremblay et al.3 9 found that 34.8 per cent survived five years as compared with 40.8 per cent of 844 patients with squamous cell carcinoma. Their treatment consisted primarily of radiation, but there is no clear evidence that the adenocarcinoma is less or more sensitive to radiation. Therefore, the same principles of diagnosis, evaluation and management apply as to squamous cell carcinoma. CANCER OF THE CERVIX IN PREGNANCY. Cancer of the cervix in pregnancy is uncommon but presents some difficulties in management. Up to 24 weeks of gestation the carcinoma should be treated promptly without regard to the pregnancy, since delay is likely to have serious consequences. In the first trimester, surgical treatment would appear to offer some advantage in early lesions since both the pregnancy and the cancer can be treated at once. For more advanced lesions, radiation therapy is still indicated and the only surgical problem presented may

Prim ary and Recurrent Cancer of the Uterus

537

be that of mana ging the abor tion whic h inevi tably occurs. In the second trime ster, again , both objec tives are achie ved by surgical thera py in early disease. If radia tion is used , hyste rotom y is indic ated befor e treat ment is begu n. In the last trime ster it is prob ably advis able to perm it the fetus to reach viabi lity (32 to 34 weeks) befor e definitive treat men t of the carci noma . Cesa rean secti on is then the proce dure of choice, followed by treat men t of the carci noma acco rding to the stage . Cesa rean secti onradic al hyste recto my may be perfo rmed or the deliv ery may be followed later by radia tion thera py acco rding to the stage of the disease. The prognosis in carci noma of the cervi x durin g preg nanc y is simil ar to that when the wom an is not preg nant P Dela y in diagnosis is a parti cular haza rd in preg nanc y. RECURRENT OR RADIORESISTANT CARCINOM A. Re-ir radia tion and chem other apy can offer little to the wom an whose canc er has not respon ded to radia tion or has recur red. Oper ative treat men t in the form of radic al hyste recto my or pelvic exen terat ion may give some wom en their only chan ce of survi val. Seve ral cond ition s need to be prese nt befor e radic al surge ry shou ld even be conte mpla ted for recu rrent carci noma of the cervix. First , patho logic al evide nce of activ e growing tumo r must be obtai ned. Second, there must be a chan ce of cure: there is little place for a palli ative exen terat ion. Thir d, the patie nt and her fami ly must unde rstan d and acce pt the proc edur e: this inclu des the possi bility of exen terat ion whic h must alwa ys be enter taine d in any surgi cal appr oach to this prob lem. Lastl y, the patie nt's circu msta nces and emot ional statu s must be such as to enab le her to take care of herse lf and the stom ata whic h may resul t. The most difficult of the abov e requ irem ents is often to obta in evidence of activ ely grow ing tumo r. The value of vario us type s of cytologic studi es is as yet unce rtain . It is impo rtant to follow patie nts closely by pelvic exam inati ons and clinical evalu ation . Incre ase in the size of a lesion and nodu larity are impo rtant in the diagnosis of recur rence . Biopsies shou ld be take n wher e indic ated and even needle biop sy of the para metr ium may be usefu l in certa in insta nces. 29 In spite of all possible care, it is frequ ent for the tragi c triad of sciat ic pain, leg swell ing and urete ral obstr uctio n to deve lop befor e one's eyes. Once a decision for surgi cal treat men t has been reach ed, prop er preoper ative prep arati on is essential.3 3 At oper ation there are sever al steps whic h shou ld be take n in logical orde r to deter mine whet her a given lesion is resec table . First , the patie nt shou ld be exam ined unde r anesthesi a. Next , the perit onea l cavit y shou ld be caref ully inves tigat ed and any suspicious para- aorti c node s remo ved for frozen secti on exam inati on. A diagnosis of meta stati c carci noma shou ld precl ude furth er oper ation . Lastl y, gentl e disse ction shou ld be perfo rmed anter iorly and on the most adhe rent side to see if the lesio n is mova ble befor e vital struc tures such as the urete r or sigm oid colon are divid ed. Ther e is a natu ral tende ncy

MICHAEL

538

N EW'l'ON

on the part of the operator to want to preserve as much normal function as possible. However, when operation for recurrent disease is performed, it is usually better to err on the side of radical rather than conservative treatment. Thus, a total or anterior exenteration is more likely to be curative than a difficult radical hysterectomy. A posterior exenteration is rarely indicated. A combined abdominoperineal approach is preferable although it is possible to complete all the dissection from above. The ureters are most satisfactorily handled by transplantation into an isolated loop of ileum or possibly into an isolated sigmoid loop. Although ureterocolic anastomosis is quicker, it carries increased danger of ascending infection and electrolyte imbalance. 27 Pelvic exenteration carries an operative mortality of 10 to 30 per cent or even higher, varying according to different investigators and according to the extent of the procedure. 26 Five-year survival rates usually range from 15 to 25 per cent. 26 The postoperative course is often stormy. In a series of 150 exenterations, Bricker et al.3 found 94 early complications in 69 patients (46 per cent). Most frequent were wound infections and intestinal obstruction. After discharge from the hospital these patients require careful supervision and rehabilitation. Bricker et al. noted 59 late complications in 40 out of 135 patients (30 per cent). Prominent among these were pyelonephritis and difficulties connected with the ileal or colonic stomata. CANCER OF THE CORPUS UTERI

Cancer of the corpus uteri ranks second to that of the cervix in malignant tumors of the female genital tract. The relative frequency of the two lesions is of some interest. Earlier data suggested that seven or eight cervical cases were found for each corpus cancer. Recent authors have suggested that in the United States this ratio is now three or two to one or even lower. Statistics vary with the type of institution in which they are collected, but two reasons for a change in the ratio might be the increasing age of the population (since corpus cancer is a disease of older women) and the earlier diagnosis and treatment of carcinoma of the cervix in many areas as a result of mass screening techniques. The commonest type of cancer of the corpus is adenocarcinoma of the endometrium. Less common are adeno-acanthoma, in which squamous metaplasia of some of the adenomatous elements takes place, sarcoma and mixed mesodermal tumors. Diagnosis and Evaluation

Diagnosis is facilitated by a sense of suspicion on the part of both patient and physician. A tendency to delay the report of postmenopausal bleeding as well as the avoidance of examinations during an episode of bleeding may lead to tragic consequences. Cytologic studies are of limited

Primary and Recurrent Cancer of the Uterus

539

value since they are positive in only about 50 per cent of cases. Endometrial biopsy may occasionally be helpful, particularly in advanced cases where definite localization of the site of the tumor is not needed. However, an accurate fractional curettage combined with examination under anesthesia and cervical biopsy remain the most accurate techniques for diagnosis and for deciding the site of the tumor in the uterus and in the lower uterine segment or cervix. Sarcomas frequently present difficulties in diagnosis, since vaginal bleeding may not occur. Often, they are found only upon pathological examination of a resected uterus. Women in whom a diagnosis of carcinoma of the corpus has been made should receive a work-up and combined evaluation similar to that used for carcinoma of the cervix. Particularly important is the evaluation of the patient as an operative risk, since many of these women are elderly. obese, hypertensive and may be diabetic. It is most important to obtain a precise diagnosis and have the patient properly studied before treatment is decided. In carcinoma of the cervix, clinical staging of the disease prior to treatment is a valuable aid in planning therapy and in offering a prognosis. In carcinoma of the corpus such staging has not yet been found so helpful and several classifications have been suggested. 18 Of recent interest is that proposed by Gusberg et al./ 2 which omits any consideration of operability but includes provision for differentiation of the tumor on microscopic examination and for involvement of the cervix: STAGE STAGE STAGE STAGE

I.

Uterus normal in size. The cervix is uninvolved and the tumor differentiated. II. The uterus is mildly enlarged, up to the size of a 272 months' pregnancy or more than 10 em. in depth. III. Uterus markedly enlarged: over size of 3 months' pregnancy or more than 10 em. in depth. IV. Bowel or bladder involved. Distant metastases.

In each instance the stage is advanced one for anaplastic tumor and/or involvement of the cervix: Treatment

ADENOCARCINOMA OF THE ENDOMETRIUM. The two techniques of treatment commonly used today are a primary surgical approach and various combinations of radiation and surgical therapy. Of the latter, probably the most widely employed is the preliminary insertion of radium into the uterine cavity, followed in four to six weeks by a total hysterectomy and bilateral salpingo-oophorectomy with removal of a wide vaginal cuff. The extent of surgical treatment varies. Often it consists only of total hysterectomy, bilateral salpingo-oophorectomy and excision of the upper part of the vagina. However, Parsons and Cesare34 point out that this may not be sufficient for several reasons. These include the possible

540

MICHAEL NEWTON

spread of the lesion through all or part of the myometrium and into the parametrium, which cannot easily be determined by preoperative examination, the chance of involvement of the vagina, and the contingency of lymph node metastases (up to 25 per cent). These authors recommend radical hysterectomy of the type used for carcinoma of the cervix with wide dissection of the parametria, pelvic lymphadenectomy and excision of the upper one-third of the vagina. Primary surgery has advantages which have been summarized by Javert and Douglas.15 The treatment is completed at one time, particularly when the disease is localized to the endometrium or superficial layers of the myometrium. The theoretical disadvantages of preoperative radium are avoided-in that its cancericidal effect may not extend beyond the myometrium, that active tumor is often found in the endometrium at the time of operation several weeks later and that the incidence of vaginal metastases may not be reduced. The disadvantages of primary radical surgery of the magnitude used for carcinoma of the cervix are: (1) many patients with this disease are poor operative risks, and such a major procedure may be hazardous; (2) such wide excision may not be necessary for the early lesion, and (3) where extension outside the confines of the uterus has occurred, the bulk of the uterus and particularly of the lower uterine segment makes dissection difficult. Apart from the theoretical disadvantages mentioned above, the preliminary application of radium frequently reduces the size of the uterus. This makes the subsequent operative procedure simpler. The disadvantages of applying radium in this manner consist first of the difficulty of filling the large uterus completely with radium and of packing enough radium into the smaller uterus. Second, the measurement of radiation dosage is difficult. Finally, the preliminary use of radium exposes the poor-risk patient to a period of waiting and to at least two anesthetics. We have adopted an approach along the lines suggested by Gusberg et al. 12 which utilizes both methods of therapy, each on specific indications. Thus, in the Stage I lesion, where the uterus is small, there is no involvement of the cervix and the tumor is well-differentiated, it is likely that either method will be successful: this fact probably accounts for the good results obtained in series where patients are seen early and where "planned" or "ideal" treatment can be used. When surgery is used (and our preference is for this in the good-risk patient), it should not be the routine simple hysterectomy. The parametria should be widely dissected, the ureterovesical angle exposed and the upper onethird of the vagina removed. Under these conditions lymphadenectomy may be unnecessary. In the event of evidence of unexpected extension found in the pathological specimen, postoperative deep x-ray therapy should be given. For Stages II and III, preliminary application of

Primary and Recurrent Cancer of the Uterus

541

radium is preferred. The Heyman applicators are used. Recent modifications in this apparatus suggested by Kraemer and Lewis19 may be helpful. The additional application of radium (in plastic ovoids) to the vagina is likely to be of value, particularly if there is evidence of cervical or vaginal involvement. Hysterectomy is performed six to eight weeks later (earlier than this may be practical). This operative procedure is not as radical as that described above, but the upper 2 em. of the vagina is excised although no attempt is made to perform a wide parametrial dissection. Occasionally a more radical procedure including lymphadenectomy is indicated in these cases, particularly if the cervix is involved. ·If the patient is a poor operative risk the insertion of radium may be repeated or may be supplemented by deep x-ray therapy. For Stage IV lesions x-ray therapy to the pelvis, possibly followed by the application of radium, is used. Overall five year survival rates are of the order of 60 to 70 per cent, somewhat higher than those for cancer of the cervix. In early and favorable cases even better results may be obtained. ADENO-ACANTHOMA. The incidence of this tumor, in which squamous and adenomatous elements co-exist, has been variously reported to be from very low up to 20 per cent22 and 24 per cent. 6 It appears to be responsive to radiation and to have characteristics similar to the adenocarcinoma. The results of treatment vary. Novak and Nalley30 had excellent results in 16 cases, with survival in 15. More recently Liggins and Way 22 noted a 27.6 per cent relative five-year survival as compared with 54.5 per cent for adenocarcinoma. Similar differences were noted by Chanen (59 per cent and 73 per cent respectively). 6 In the absence of further evidence, it has been our practice to treat these lesions in the same way as adenocarcinoma. SARCOMA. This includes those tumors in which sarcomatous change has occurred in a myoma and those in which a sarcoma has arisen primarily in the myometrium. If the diagnosis can be made preoperatively (which is rare), total hysterectomy and bilateral salpingo-oophorectomy should be performed. More radical procedures are not indicated. Often the diagnosis is suspected at the time of operation for myomas, and the soft spongy sarcoma may be confused with a pregnant uterus in the woman of reproductive age. The prognosis is generally poor except for those sarcomas found incidentally in a myoma. These tumors are not responsive to radiation and as yet chemotherapy has little to offer. MIXED MESODERMAL TuMORS. This is an unusual mali!!;nant neoplasm which is thought to arise from the epithelial stroma of the endometrium, endocervix or the upper vaginal epithelium of children. This primitive tissue may develop into epithelial and sarcomatous elements and these changes are frequently multicentric in origin. It is a disease of the very old or very young, and is uncommon in women of reproductive age. The polypoid structure of some of these tumors has given rise to the term "sarcoma botryoides."

MICHAEL NEWTON

542

The diagnosis of a mixed mesodermal tumor is often made only after thorough pathological examination of a removed uterus. The inability to make an early diagnosis accounts in part for the very poor prognosis in patients with this tumor. Thus, Krupp et al.,2 1 in a series of 51 patients, noted 49 deaths within two years and the longest survival was 331; years. If a preoperative diagnosis can be made, the best treatment would appear to be a radical hysterectomy with pelvic lymphadenectomy. When the tumor is discovered in the resected specimen, radiation therapy has little to offer. Chemotherapy provides some hope for these women, but at present no entirely satisfactory agent is known. RECURRENT CARCINOMA. Carcinoma of the corpus may recur locally or be widely disseminated through the body. The most common site for local recurrence is the vagina. When a solitary metastasis is present in this area, local application of radium with or without external radiation therapy may be curative. Rarely, vaginectomy is indicated. When the disease recurs within the pelvis and distant metastases can be excluded, radical surgery can occasionally be offered to the patient. The same considerations apply as in recurrent or radioresistant carcinoma of the cervix. In a series of 33 patients with recurrent disease, subjected to pelvic exenteration, Brunschwig6 recorded six five-year survivals (18 per cent). In the long run, chemotherapy may have something to offer these patients. SUMMARY

Although cancer of the cervix uteri and of the corpus uteri have different characteristics, the same principles of diagnosis and evaluation apply to both. A tissue diagnosis must be obtained before treatment is begun. A basic work-up and a combined evaluation by those concerned in treatment are essential if the individual patient is to receive the best care. The role of surgical treatment in carcinoma of the cervix has increased in importance in recent years because of the wider applicability of radical hysterectomy for primary treatment and of exenteration for recurrent or radioresistant disease. In addition, opportunities for surgical management of the complications of the disease and its treatment are increasing. However, radiation therapy remains very effective, especially in more advanced lesions. Combinations of radiation and surgical therapy are being tried in various centers and will need further time for proper evaluation. As yet, chemotherapy has little to offer the patient with cervical cancer. In carcinoma of the endometrium, increasing information is becoming available on the factors influencing prognosis. In the early lesion primary surgical therapy, in the form of modified radical hysterectomy with bilateral salpingo-oophorectomy, appears to be of some advantage. When

Primary and Recurrent Cancer of the Uterus

543

the disease is more advanced, preliminary radiation therapy by the insertion of radium, followed by a total hysterectomy and bilateral salpingo-oophorectomy, may be used. In the patient who is a very poor operative risk, radiation therapy alone is of some benefit. As yet, surgical treatment provides the only management for patients with uterine sarcomas or mixed mesodermal tumors. REFERENCES 1. Atlee, H. B. and Tupper, C.: The Vaginoabdominal Approach in Radical Pelvic Surgery. Am. J. Obst. & Gynec. 73: 141, 1957. 2. Blaikley, J. B., Kottmeier, H. L., Martius, H. and Meigs, J. V.: Classification and Clinical Staging of Carcinoma of the Uterus. Am. J. Obst. & Gynec. 75: 1286, 1958. 3. Bricker, E. M., Butcher, H. R. Jr., Lawler, W. H. Jr. and McAfee, C. A.: Surgical Treatment of Advanced and Recurrent Cancer of the Pelvic Viscera. Ann. Surg. 152: 388, 1960. 4. Brunschwig, A.: Radical Vaginal Operation (Schauta) for Carcinoma of Cervix. Am. J. Obst. & Gynec. 66: 153, 1953. 5. Brunschwig, A.: Surgical Treatment of Recurrent Endometrial Cancer. Obst. & Gynec. 18: 272, 1961. 6. Chanen, W.: A Clinical and Pathological Study of Adenoacanthom a of the Uterine Body. J. Obst. & Gynaec. Brit. Emp. 67: 287, 1960. 7. Claiborne, H. A., Thornton, W. N. and Wilson, L.A. Jr.: Pelvic Lymphadenectomy for Carcinoma of the Uterine Cervix. Am. J. Obst. & Gynec. 80: 672, 1960. 8. Creadick, R.N.: Carcinoma of the Cervical Stump. Am. J. Obst. & Gynec. 75: 565, 1958. 9. Gorton, G.: Postirradiation Prophylactic Extraperitoneal Lympha-"enectomy in Carcinoma of the Uterine Cervix. Acta radiol. suppl. 100: 1, 1953. 10. Gray, M. J., Gusberg, S. B. and Guttman, R.: Pelvic Lymph Node Dissection Following Radiotherapy. Am. J. Obst. & Gynee. 76: 629, 1958. 11. Greiss, F. C., Blake, D. D. and Lock, F. R.: Treatment of Cancer of the Cervix by Radiation and Elective Radical Hysterectomy. Am. J. Obst. & Gynec. 82: 1042, 1961. 12. Gusberg, S. B., Jones, H. C. Jr. and Tovell, H. M. M.: Selection of Treatment for Corpus Cancer. Am. J. Obst. & Gynec. 80: 374, 1960. 13. Hollenbeck, Z. J. R.: Carcinoma of the Cervix-Treatm ent by Radical Hysterectomy Following Central Irradiation. Am. J. Obst. & Gynec. 79: 944, 1960. 14. Howkins, J.: Synchronous Combined Abdomino-vaginal Hysterocolpecto my for Cancer of the Cervix-A Report of Fifty Patients. J. Obst. & Gynaec. Brit. Emp. 66: 212, 1959. 15. Javert, C. T. and Douglas, R. G.: Treatment of Endometrial Adenocarcinoma: A Study of 381 Cases at the New York Hospital; A Preliminary Report. Am. J. Roentgenol. 75: 508, 1956. 16. Kelso, J. W.: Surgical Management of Carcinoma of the Cervix. South. M. J. 52: 681, 1959. 17. Kinch, R. A. H.: Factors Affecting the Prognosis of Cancer of the Cervix in Pregnancy. Am. J. Obst. & Gynec. 82: 45, 1961. 18. Kottmeier, H. L.: Carcinoma of the Corpus Uteri: Diagnosis and Therapy. Am. J. Obst. & Gynec. 78: 1127, 1959. 19. Kraemer, D. W. and Lewis, G. C. Jr.: Multiple-Source Intracavitary Radium Applicator. Obst. & Gynec. 13: 614, 1959. 20. Krieger, J. S. and McCormack, L. J.: Individualizatio n of Therapy for Cervical Carcinoma in Situ. Surg. Gynec. & Obst. 109: 328, 1959. 21. Krupp, P. J., Sternberg, W. H., Clark, W. H., St. Romain, M. J. Jr. and Smith,

544 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38.

39. 40.

MICHAEL NEWTON

R. C.: Malignant Mixed Mullerian Neoplasms (Mixed Mesodermal Tumors). Am. J. Obst. & Gynec. 81: 959, 1961. Liggins, G. C. and Way, S.: Comparison of the Prognosis of Adenoacanthoma and Adenocarcinoma of the Corpus Uteri. J. Obst. & Gynaec. Brit. Emo. 67. 294, 1960. McCall, M. L.: Radical Vaginal Operative Approach in the Treatment of Carcinoma of the Cervix. Am. J. Obst. & Gynec. 78: 712, 1959. McCall, M. L., Keaty, E. C. and Thompson, J. D.: Conservation of Ovarian Tissue in the Treatment of Carcinoma of the Cervix with Radical Surgery. Am. J. Obst. & Gynec. 75: 590, 1958. Meigs, J. V.: Surgical Treatment of Cancer of the Cervix. New York, Grune & Stratton, 1954. Mikuta, J. J.: Pelvic Exenteration in Carcinoma of the Cervix. A Review of the Literature. Am. J. M. Sc. 236: 797, 1958. Murphy, J. J. and Mikuta, J. J.: Urinary Diversion in Pelvic Exenteration. Surg. Gynec. & Obst. 112: 743, 1961. Newton, M. and Bolten, K. A.: Carcinoma of the Cervix: Diagnosis and Evaluation. J. Mississippi State M. A. 2: 239, 1961. Newton, M., Hickman, B. T. and Bolten, K. A.: Carcinoma of the Cervix: Treatment and Follow-Up. J. Mississippi State M. A. 2: 279, 1961. Novak, E. R. and Nalley, W. B.: Uterine Adenoacanthoma. Obst. & Gynec. 9: 396, 1957. Novak, F.: Procedure for the Reduction of the Number of Ureterovaginal Fistulas Mter Wertheim's Operation. Am. J. Obst. & Gynec. 72: 506, 1956. Parker, R. T. and others: Intraepithelial (Stage O) Cancer of the Cervix. Am. J. Obst. & Gynec. 80: 693, 1960. Parsons, L.: p. 322 ff. in Meigs, J. V. (Ed.): Surgical Treatment of Cancer of the Cervix. New York, Grune & Stratton, 1954. Parsons, L. and Cesare, F.: Wertheim Hysterectomy in the Treatment of Endometrial Carcinoma. Surg. Gynec. & Obst. 108: 582, 1959. Riva, H. L., Andreson, P. S., Hathaway, C. R. Jr., DesRosiers, J. L. and Stoehr, N. U.: Surgical Experience in Cancer of the Cervix. Am. J. Obst. & Gynec. 82: 64, 1961. Rutledge, F. N. and Fletcher, G. H.: Transperitoneal Pelvic Lymphadenectomy Following Supervoltage Irradiation for Squamous-Cell Carcinoma of the Cervix. Am. J. Obst. & Gynec. 76: 321, 1958. Simmonds, R. J.: Vaginoabdominal Approach to Pelvic Cancer Surgery. Obst. & Gynec. 7: 527, 1956. Stevenson, C. S.: The Combined Treatment of Carcinoma of the Cervix with Full Irradiation Therapy Followed by Radical Pelvic Operation (Second Progress Report on a Series Now Numbering 95 Cases). Am. J. Obst. & Gynec. 81: 156, 1961. Tremblay, P. C., Latour, J. P. A. and Dodds, J. R.: Adenocarcinoma of the Cervix Uteri. Obst. & Gynec. 15: 299, 1960. Yagi, H.: Extended Abdominal Hysterectomy with Pelvic Lymphadenectomy for Carcinoma of the Cervix. Am. J. Obst. & Gynec. 69: 33, 1955.

2500 North State Street Jackson 6, Mississippi