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Variations in response to therapy for cervical cancer
Variations
in response to therapy for cervical
cancer JOHN Skokie,
H.
ISAACS,
M.D.
Illinois
Comparisons of salvage rates are usually based on the therapeutic techniques and clinical staging. Little attention is given to the quality of clinical material. Various clinics treat patients of dilferent heredity, dietary, social, and economic backgrounds. The end results of two series of patients treated in the same county institution are compared. The first group was treated in a haphazard fashion with an over-all salvage rate of 29.4 per cent (Stage I60.4 per cent). The second group was managed by a gynecologic tumor board. The over-all salvage rate was 33.0 per cent (Stage I61.2 per cent). Another comparison was made between the above clinic population and a group of patients treated in a private institution. Both groups were managed by a tumor board. The over-all salvage rate in the clinic group zvas 33.0 per cent (Stage I 61.2 per cent, Stage II 38.8 per cent). In the private group, the over-all salvage rate was 60.4 per cent (Stage I 93.5 per cent, Stage II 75.0 per cent). Possible explanations for these discrepancies are presented in the text.
Fo R THE P AS T sixty years, there has been a steady rise in the five-year cure rate for cervical malignancy. Early diagnosis and better therapy are primarily responsible for this improvement. Poor survival statistics are usually attributed to inadequate therapy administered by inexperienced personnel. The obvious solution, therefore, should be to treat all cancer patients in well-equipped, well-staffed oncology centers. Cervical cancer treated in such a fashion would theoretically eliminate deaths from this particular malignancy. Most of us, however, are acquainted with an “exceptional” cancer patient. The one who, in spite of totally inadequate therapy, has continued to thrive. Conversely, the patient with an early cervical lesion, who receives excellent therapy, may fail to respond and progress rapidly downhill. Such conflicting results are difficult to explain, but it does suggest that the dietary, heredity, economic, and social background of the patient, in addition to the virulence of Presented at the Pittsburgh and Gynecological Society $ityi;;gh, Pennsylvania, I .
the tumor and extent of the disease, is an important element in the response to therapy. Most large series represent a kaleidoscopic pattern of patient material and do not separate cases in any manner except by stage of the disease. Since the salvage rate is determined by treatment and clinical material, comparison of end results from different centers is impossible unless the clinical material is equitable. These same observations have been noted by others31 6, I2 The purpose of this report is twofold. One is to demonstrate the difference in results between those patients recently treated and a similar clinical population treated twenty years ago. Second, and of greater importance, is to compare the salvage rates of two varying clinical groups treated concurrently and in a similar fashion. In 1954, Schmitz and associates13 reported on the haphazard treatment of cervical cancer in a large city hospital. The period studied was from 1940 through 1946, during which time there were 602 patients with cervical cancer treated at Cook County Hospital in Chicago. Three hundred and fifty-seven of these patients were followed
Obstetrical Meeting, October 390
Volume Number
110 3
Therapy
140
40
20
0
I
II
III
Fz
SECONDARY
STAGE OF DISEASE
Fig. 1. Four hundred and thirty patients treated at Cook County July 1, 1965, to June 30, 1970.
cervical Hospital
cancer from
for five years or more, or until their death. Of those followed, there were 124 Stage I lesions with a 60.4 per cent survival rate; there were 109 Stage II lesions with a 21.1 per cent survival rate; and there were 124 cases of Stage III and IV lesions with a 5.6 per cent five-year survival. The over-all five)-ear determinate survival rate was 29.4 per cent. The determinate survival rate means the percentage of patients that surLive a given time when a selected group of patients is considered. Those patients classified as indeterminate are: (1) those lost to follow-up, (2) those seen in consultation only, and (3) those dying of other causes without neoplastic disease. These survival rates were, by the usual criteria, definitely substandard. Schmitz and associates concluded that if such results were to be improved upon a tumor service would have to he developed and should include a pathologist, radiotherapist, and a gynecologist. This tumor board would then evaluate and treat ~11 gynecologic cancer patients admitted to the hospital. On July 1, 1965, almost twelve years later, such a tumor service was established. Since that time, all patients with pelvic can-
response
variations
in cervical
cancer
391
cer admitted to Cook County Hospital have been referred to the tumor service. Prior to the initiation of therapy: a thorough Incdical evaluation is undertaken. The evalllstion includes the usual history, and physical and laboratory studies plus adequate biopsy. In addition to this, proctoscopy, cystnscopy, gastrointestinal x-ray studies, and roentgen bone survey are performed to complete an adequate tumor work-up. This new oncology division has now passed its fifth birthday, and thus it is possible to analyze some of the results. Although there is an insufficient number of patients who have passed the five-year mark since their original therapy, there is a suflicient number that have gone beyond the two-year mark for preliminary analysis. Using a twoyear survival rate seems justified since in most series approximately three quarters of the deaths occur in the first two years and eighty-five to ninety per cent occur in the first three years. Material Since the establishment of the tumor service, 430 patients with cervical cancer have been treated. The grouping as shown in Fig. 1 reflects the type of patient with cervical cancer seen at Cook County Hospital. The patients treated secondarily (shown in Fig. 1 as Secondary) had received some form of therapy elsewhere before being referred to Cook County Hospital and are not included in the statistical evaluation. The patients now being reported are in a slightly more advanced stage of their disease than in the series reported by Srhmitz and associates.13 This is a shocking observation. In the present series, only 21.4 per cent were in the Stage I category, whereas in the Schmitz series 34.7 per cent were in this early stage. The percentage of GISES in Stage II remained about the s
392
lsaacs Amer.
2 60 > i t 5 s w 5
50 40 30 20 10 n
Fig. 2. Comparison of end results of 1940 to 46 series with 1965 to 68 series. in the present series is probably economic and social. With the advent of insurance plans, Medicare, and integration, many of the patients that had previously been referred to Cook County Hospital are being treated in their own local hospitals, most of which probably do not have an organized oncology service. The ones that remain-those patients that we see at Cook County Hospitalhave nowhere else to go. These are the truly indigent patients for whom no other hospital wishes to be responsible. These are the individuals to whom certain popular writers have referred to as the “undesirable poor.” Results
and
comments
Two hundred and forty-two patients of the present series have been followed from two to five years. Fig. 2 compares the end results of the two periods. The over-all salvage rate of 33.0 per cent is a very slight improvement over the Schmitz series. In Stage I., however, the salvage rates showed virtually no change-60.4 compared to 61.2 per cent. There was noticeable improvement in Stage II cases-21 .l against 38.8 per cent survival in the present series. The survival rate in the combined Stages III and IV
June J. Obstet.
I, lYi1 Gyn~c.
lesions improved from 5.6 to 19.0 per cent in the present group. If Stages III and IV are separated, Stage III lesions show a 23.7 per cent survival, and Stage IV, a 10.8 per cent survival. It would seem, therefore, that the establishment of a tumor service did improve the survival rates, but not as much as would have been anticipated, and is far below the over-all survival of 49.1 per cent reported by the American Cancer Society. The published survival rates, taken from the Cancer Prognosis Manual? of the American Cancer Society published in 1966, indicate an expected survival rate of 79.2 per cent in Stage I, 60.3 per cent in Stage II, 36.4 per cent in Stage III, and 21.1 per cent in Stage IV. In another sector of the Chicago area, widely separated both geographically and socioeconomically from Cook County HOSpital, another series of cervical cancer patients was compiled from a large private hospital. Since 1962, all patients with cervical cancer admitted to this hospital have been seen by a tumor board consisting of a pathologist, radiotherapist, and gynecologist. The author is the same gynecologist serving on the tumor board in both institutions. The same protocol was followed in both hospitals. The results are interesting and serve to emphasize the difference in end results based on clinical material. There were 86 cases treated, and these are divided into 31 Stage I cases, 28 Stage II cases, 14 Stage III cases, and 13 Stage IV cases. The two- to five-year determinate survival rate in this more affluent group of patients was 60.4 per cent. Fig. 3 illustrates the difference in salvage rates in the Stage I and II lesions in this private hospital series compared with the national average reported in the Cancer Prognosis Manual.? Those patients with more advanced lesions, i.e., Stages III and IV did not display the same marked improvement in survival. How do we explain these differences in end results? Do the poor general health and malnutrition of the patients in the indigent series alter their resistance to malignancy? Do their mistrust, suspicion, and more casual
Volume Number
100
110 3
Therapy
n
AMERICAN
m
PRIVATE
CANCER
SOCIETY
PATIENTS
1
20 IO 0 STAGE
OF
DISEASE
Fig. 3. Comparison of end results: American Cancer Society collected series versus a private hospital series. attitude account for patient delay? Does this to the development of delay contribute generally larger lesions in this group of patients even in the same International Stage reported a differof the disease? Jameson ence in outcome of treatment in New Zealanders of European descent compared to Polynesians but attributed this to delay in presenting themselves for treatment. He noted a relatively higher death rate among Polynesians in the first year after therapy. This same higher death rate during the first year post treatment was also noted by us among the impoverished group. The Polynesian’s standard of living in New Zealand and way of life are in many ways similar to that of the poor Negro in a large metropolitan area. Another factor that may be responsible for
response
variations
in cervical
cancer
393
the inferior salvage rate in the truly indigent is lack of understanding and motivation. While there is no firm statistical evidence, casual observations suggest radiation sickness is more severe in these patients and may force them to discontinue therapy prematurely. Diddle and colleagues* noted more severe reactions in a similar group of patients being irradiated for cervical carcinoma. Additionally their nutritional state render irradiation less effective. may Garcia5 reported on the poor end results in the anemic patient being treated for cervical carcinoma. Fletcher? has noted that patients with good nutritional status have a better prognosis. Although it is extremely difficult to ascertain the true nutritional state of the Cook County Hospital patients, it has been documented0 that pregnant patients in the same geographic area have a diet low in protein and iron and high in carbohydrates. The result is a high incidence of anemia and low serum-protein levels. Most of the patients served by Cook County Hospital eat “snack” foods with empty calories. This most likely caltses a chronic nutritional deficiency. Current studies are being done to investigate thB. During the past five years, in order to circumvent the problems involved in delivering a cancerocidal dose of irradiation to such impoverished individuals, the majority of Stage I and early Stage II lesions have been treated surgically at Cook C,ounty Hospital. It was anticipated that by resorting to surgical procedures our salvage: rate might be improved. It has been show1 that adequate operation or adequate radiation gives comparable end results.ll Tlx primary surgical approach in these early lesions has been a wide surgical excision (If the uterus and surrounding tissues p!us a thorough pelvic lymph node dissection as described by Louros. lo Originally, preoperative pelvic lymphangiograms were employed sporadically. The results in those patients on whom the procedure was done were equivocal as to the presence or absence of metastatic lymph nodes. The procedure did seem to help to ensure a more adstquate
394
lsaacs
Amer.
Table I. Associated preoperative complications of Stages I and II cervical cancer treated surgically. Comparison of preoperative complications between the private and clinic patients
Complication No associated complications Anemia Hypertension Kidney disease Obesity Pregnancy Heart disease Pelvic inflammatory disease Pulmonary tuberculosis Diabetes Alcoholism Drug addiction Chronic bronchitis Previous bilateral external iliac artery grafts Age range
1iigi
1ipa$~, 35 16 15 9 8 8 8 7 4 3 2 2 1
19 to 74
22
2 2
1 27 to 72
pelvic lymph node dissection. Because of this impression, pelvic lymphangiograms have been performed routinely on the last twelve private patients. A repeat roentgen examination is done before closure of the abdomen to ascertain if all of the lymph nodes have been removed. In two patients out of the twelve, the roentgenogram detected an incomplete lymph node removal. In both instances additional dissection was carried out prior to abdominal closure. Since July 1, 1965, through June 30, 1970, there were 93 radical hysterectomies performed on the gynecological tumor service at Cook County Hospital. During a somewhat longer period of time, there have been 27 cases in my private practice that were treated by radical operation. This has provided an additional opportunity to compare complications and end results in these two very different populations. The preoperative complications in the two groups are shown in Table I. Although this cannot be substantiated, these complications probably do not fully reflect the difference in the general state of health in the two groups. Postoperative complications. The post-
Table II. Comparison complications between clinic patients
June J. Obstet.
1, 1971 Gynec.
of postoperative the private and ____--
Complication No complications Bladder atony Wound infection Uterovaginal fistula Vesicovaginal fistula Wound dehiscence Pyelonephritis Lymphocyst Second operation for hemorrhage Pelvic hematoma Pelvic abscess Ileus Pulmonary embolus Sciatic nerve injury with foot drop Tumor found at edge of specimen requiring vaginectomy Radical vulvectomy and groin dissection for associated carcinoma of vulva Deaths due to surgery Postoperative days in hosuital
1
93 44 16 12 8 3 2 2 2 2 1 1 1 1 1
I-
27 12 5 4 3 1
1
3
1
6 13 to 110 11 to 37
operative complications were more numerous and severe in the Cook County Hospital patients. Table II lists the number of complications encountered in the clinic group as compared with the private series. There were six deaths in the Cook County series. Three of these deaths, namely, a death due to hypovolemia, a death of a patient who developed a uterovaginal fistula with superimposed sepsis, and a patient with an undiagnosed bowel obstruction, would probably be classified as preventable. The remaining deaths, however, should be classified as nonpreventable, and may simply be attributable to patient material, although this is philosophical. One patient died of a massive hemorrhage due to a slough of the external iliac artery; she had been discharged from the hospital on the fourteenth postoperative day in good condition. She returned thirteen days later in shock. She was taken to the operating room, and the artery was successfully repaired, but the accom-
Volume Number
Therapy
110 3
Table III.
Salvage rate of 70 patients operated upon for cervical cancer at Cook (bounty Hospital. Results of follow-up for 2 to 5 years
response
in cervical
cancer
395
Table IV. Salvage
rate of 20 patients operated upon for cervical cancer at Cook County Hospital by the author. Result> of follow-up for 2 to 5 years --____
Stape
1
variafions
‘;;,;g[ii
1-i;
I
1
Alive Dead Lost
24 17 6
58.5
Alive Dead Lost
8 10 2
44.4
22”
18 5
1
& 2
0 5 0
II
Alive Dead Lost
8
Alive Dtlad Lost
0 4 0
0
0
0
57.1
6
!”
1
4t
::
1
II
Kecurrent Alive 0 Dead 3 Lost 0 ‘One alive with disease. TTwo surgical deaths. $One
surgical
death.
$0~
surgical
death.
0 2
1
panying massive blood loss and associated sepsis proved fatal. The second patient died of a pelvic abscess. She left the hospital on the eleventh postoperative day in good condition. She returned three days later moribund. Postmortem examination revealed a huge pelvic abscess. The last patient suffered hepatic necrosis with resulting hemorrhagic diathesis and death. For twenty-four hours prior to operation (unknown to the nursing staff), she had consumed a massive quantity of alcohol. The immediate toxic effect of the ethanol, as well as prior excessive alcohol consumption, combined with the anesthesia probably produced the liver necrosis. At the time of autopsy, about 1,500 ml. of blood was found in the pleural cavity. There were also multiple kidney abscesses. The fact that she was also a heroin addict was probably contributory. The convalescence of these Cook County Hospital patients after discharge from the ward is less than ideal. Inadequate hygienic surroundings, lack of home nursing care, untimely coitus, alcohol and narcotic consumption, and ignorance all add up to the possibility of a stormy recovery.
Recurrent Alive Dead Lost
‘,4 -+
1
*One
alive
with
tone
surgical
death.
disease.
$0~
surgical
death.
The survival rates in this surgical series are far below what might have been anticipated. Of the seventy patients operated upon two to five years ago, the determinate two- to five-year survival rate in the Stage I lesions was only 58.5 per cent (Table III). A somewhat similar experience was noted with the same type of clinic material treated for recurrent carcinoma at King’s County Hospital; only 8 of 193 of their patients survived five years after therapy.* It could be suggested that such poor results would not have occurred if these Cook County women had been surgically treated by the senior attending staff rather than by residents with attending staff supervision. However, twenty of the seventy cases in the indigent series herein reported were operated upon personally by the author. The salvage rate in the Stage I lesions in this group was 57.1 per cent, a percentage virtually identical with the over-all indigent series. This is seen in Table IV. The one patient cited is preterminal. The two- to ten-year surviva1 rat<: of 18 patients in the author’s private practice was 93.7 per cent. The one patient who died of
396 lsaacs
recurrent disease did not receive postoperative irradiation even though a positive node was found. The material presented demonstrates differences in survival rates based on clinical material. I cannot explain why such a discrepancy exists but have shown only that it does exist. Perhaps well-planned prospective studies could help to discover the actual factors that account for these staggering differences. It might be worthwhile to postpone treatment in the indigent patient for a month or more. During this time they could be housed in a “diagnostic pretreatment compound.” In such an environment in addition to the usual tumor work-up, their nutritional, social, and physical state might be
REFERENCES
1.
Calame, R. J.: AMER. J. OBSTET. GYNEC. 105: 380, 1969. 2. Diddle, A. W., Davis, M., O’Connor, K. A., and Brown, B.: AMER. J. OBSTET. GYNEC. 71: 768, 1956. 3. Fletcher, G. H.: Cancer of the Uterus and Ovary, Chicago, 1969, Year Book Medical Publishers, Inc., p. 192. 4. Fletcher, G. H.: Uterine cervix, in Textbook of Radiotherapy, chap. 10, Philadelphia, 1966, Lea & Febiger, Publishers. 5. Garcia, M.: The Effect of Anemia and Uropathy on the Curability of Carcinoma of the Cervix. Read before 58th Annual Meeting, American Roentgen Ray Society, 1957. 6. Graham, J. B., Sotto, L. S. J., and Paloncek, F. P.: Carcinoma of the Cervix, Philadelphia, 1962, W. B. Saunders Company.
Amer.
June J. Obstet.
1, 1971 Gynec.
vastly improved. Good hygiene, nourishing food, isolation from the stresses of their ordinary type of existence, and patient and understanding counseling in comfortable surroundings might add more to improved salvage rates than simply an efficient medical evaluation and an immediate institution of therapy. Would this be more costly? Probably not. The average Stage IV cervical cancer patient lives about 13 months, during which time the suffering and medical expense can be astronomical. Much of this expense is born by the state, and the end result is tragedy. If this same financial expenditure could be utilized for proper pretreatment preparations, the cost might be lowered and the end result more gratifying.
7.
James, A. G.: Cancer Prognosis Manual, 1966, American Cancer Society, Inc., p. 59. 8. Tameson. M. H.: Aust. New Zeal. ”T. Obstet. “Gynaec.‘% 258, 1969. 9. Keith, L., Evenhouse, H., and Webster, A.: Obstet. Gynec. 32: 415, 1968. 10. Louros. N. Cl.: Int. T. Gvnec. Obstet. 8: 62, 1970. 11. Masubuchi, K., Tenjin, Y., Kubo, H., and Kimura, M.: AMER. J. OBSTET. GYNEC. 103: 566, 1969. 12. Rotkin, I. D., and Cameron, J. R.: Cancer 21: 663, 1968. 13. Schmitz, H. E., Geiger, C. A., Smith, C. J., and Bleichert, P. A.: Obstet. Gynec. 4: 75, 1954. ”
64 Old Skokie,
Orchard Illinois
60076
I
in response to therapy for cervical
cancer JOHN Skokie,
H.
ISAACS,
M.D.
Illinois
Comparisons of salvage rates are usually based on the therapeutic techniques and clinical staging. Little attention is given to the quality of clinical material. Various clinics treat patients of dilferent heredity, dietary, social, and economic backgrounds. The end results of two series of patients treated in the same county institution are compared. The first group was treated in a haphazard fashion with an over-all salvage rate of 29.4 per cent (Stage I60.4 per cent). The second group was managed by a gynecologic tumor board. The over-all salvage rate was 33.0 per cent (Stage I61.2 per cent). Another comparison was made between the above clinic population and a group of patients treated in a private institution. Both groups were managed by a tumor board. The over-all salvage rate in the clinic group zvas 33.0 per cent (Stage I 61.2 per cent, Stage II 38.8 per cent). In the private group, the over-all salvage rate was 60.4 per cent (Stage I 93.5 per cent, Stage II 75.0 per cent). Possible explanations for these discrepancies are presented in the text.
Fo R THE P AS T sixty years, there has been a steady rise in the five-year cure rate for cervical malignancy. Early diagnosis and better therapy are primarily responsible for this improvement. Poor survival statistics are usually attributed to inadequate therapy administered by inexperienced personnel. The obvious solution, therefore, should be to treat all cancer patients in well-equipped, well-staffed oncology centers. Cervical cancer treated in such a fashion would theoretically eliminate deaths from this particular malignancy. Most of us, however, are acquainted with an “exceptional” cancer patient. The one who, in spite of totally inadequate therapy, has continued to thrive. Conversely, the patient with an early cervical lesion, who receives excellent therapy, may fail to respond and progress rapidly downhill. Such conflicting results are difficult to explain, but it does suggest that the dietary, heredity, economic, and social background of the patient, in addition to the virulence of Presented at the Pittsburgh and Gynecological Society $ityi;;gh, Pennsylvania, I .
the tumor and extent of the disease, is an important element in the response to therapy. Most large series represent a kaleidoscopic pattern of patient material and do not separate cases in any manner except by stage of the disease. Since the salvage rate is determined by treatment and clinical material, comparison of end results from different centers is impossible unless the clinical material is equitable. These same observations have been noted by others31 6, I2 The purpose of this report is twofold. One is to demonstrate the difference in results between those patients recently treated and a similar clinical population treated twenty years ago. Second, and of greater importance, is to compare the salvage rates of two varying clinical groups treated concurrently and in a similar fashion. In 1954, Schmitz and associates13 reported on the haphazard treatment of cervical cancer in a large city hospital. The period studied was from 1940 through 1946, during which time there were 602 patients with cervical cancer treated at Cook County Hospital in Chicago. Three hundred and fifty-seven of these patients were followed
Obstetrical Meeting, October 390
Volume Number
110 3
Therapy
140
40
20
0
I
II
III
Fz
SECONDARY
STAGE OF DISEASE
Fig. 1. Four hundred and thirty patients treated at Cook County July 1, 1965, to June 30, 1970.
cervical Hospital
cancer from
for five years or more, or until their death. Of those followed, there were 124 Stage I lesions with a 60.4 per cent survival rate; there were 109 Stage II lesions with a 21.1 per cent survival rate; and there were 124 cases of Stage III and IV lesions with a 5.6 per cent five-year survival. The over-all five)-ear determinate survival rate was 29.4 per cent. The determinate survival rate means the percentage of patients that surLive a given time when a selected group of patients is considered. Those patients classified as indeterminate are: (1) those lost to follow-up, (2) those seen in consultation only, and (3) those dying of other causes without neoplastic disease. These survival rates were, by the usual criteria, definitely substandard. Schmitz and associates concluded that if such results were to be improved upon a tumor service would have to he developed and should include a pathologist, radiotherapist, and a gynecologist. This tumor board would then evaluate and treat ~11 gynecologic cancer patients admitted to the hospital. On July 1, 1965, almost twelve years later, such a tumor service was established. Since that time, all patients with pelvic can-
response
variations
in cervical
cancer
391
cer admitted to Cook County Hospital have been referred to the tumor service. Prior to the initiation of therapy: a thorough Incdical evaluation is undertaken. The evalllstion includes the usual history, and physical and laboratory studies plus adequate biopsy. In addition to this, proctoscopy, cystnscopy, gastrointestinal x-ray studies, and roentgen bone survey are performed to complete an adequate tumor work-up. This new oncology division has now passed its fifth birthday, and thus it is possible to analyze some of the results. Although there is an insufficient number of patients who have passed the five-year mark since their original therapy, there is a suflicient number that have gone beyond the two-year mark for preliminary analysis. Using a twoyear survival rate seems justified since in most series approximately three quarters of the deaths occur in the first two years and eighty-five to ninety per cent occur in the first three years. Material Since the establishment of the tumor service, 430 patients with cervical cancer have been treated. The grouping as shown in Fig. 1 reflects the type of patient with cervical cancer seen at Cook County Hospital. The patients treated secondarily (shown in Fig. 1 as Secondary) had received some form of therapy elsewhere before being referred to Cook County Hospital and are not included in the statistical evaluation. The patients now being reported are in a slightly more advanced stage of their disease than in the series reported by Srhmitz and associates.13 This is a shocking observation. In the present series, only 21.4 per cent were in the Stage I category, whereas in the Schmitz series 34.7 per cent were in this early stage. The percentage of GISES in Stage II remained about the s
392
lsaacs Amer.
2 60 > i t 5 s w 5
50 40 30 20 10 n
Fig. 2. Comparison of end results of 1940 to 46 series with 1965 to 68 series. in the present series is probably economic and social. With the advent of insurance plans, Medicare, and integration, many of the patients that had previously been referred to Cook County Hospital are being treated in their own local hospitals, most of which probably do not have an organized oncology service. The ones that remain-those patients that we see at Cook County Hospitalhave nowhere else to go. These are the truly indigent patients for whom no other hospital wishes to be responsible. These are the individuals to whom certain popular writers have referred to as the “undesirable poor.” Results
and
comments
Two hundred and forty-two patients of the present series have been followed from two to five years. Fig. 2 compares the end results of the two periods. The over-all salvage rate of 33.0 per cent is a very slight improvement over the Schmitz series. In Stage I., however, the salvage rates showed virtually no change-60.4 compared to 61.2 per cent. There was noticeable improvement in Stage II cases-21 .l against 38.8 per cent survival in the present series. The survival rate in the combined Stages III and IV
June J. Obstet.
I, lYi1 Gyn~c.
lesions improved from 5.6 to 19.0 per cent in the present group. If Stages III and IV are separated, Stage III lesions show a 23.7 per cent survival, and Stage IV, a 10.8 per cent survival. It would seem, therefore, that the establishment of a tumor service did improve the survival rates, but not as much as would have been anticipated, and is far below the over-all survival of 49.1 per cent reported by the American Cancer Society. The published survival rates, taken from the Cancer Prognosis Manual? of the American Cancer Society published in 1966, indicate an expected survival rate of 79.2 per cent in Stage I, 60.3 per cent in Stage II, 36.4 per cent in Stage III, and 21.1 per cent in Stage IV. In another sector of the Chicago area, widely separated both geographically and socioeconomically from Cook County HOSpital, another series of cervical cancer patients was compiled from a large private hospital. Since 1962, all patients with cervical cancer admitted to this hospital have been seen by a tumor board consisting of a pathologist, radiotherapist, and gynecologist. The author is the same gynecologist serving on the tumor board in both institutions. The same protocol was followed in both hospitals. The results are interesting and serve to emphasize the difference in end results based on clinical material. There were 86 cases treated, and these are divided into 31 Stage I cases, 28 Stage II cases, 14 Stage III cases, and 13 Stage IV cases. The two- to five-year determinate survival rate in this more affluent group of patients was 60.4 per cent. Fig. 3 illustrates the difference in salvage rates in the Stage I and II lesions in this private hospital series compared with the national average reported in the Cancer Prognosis Manual.? Those patients with more advanced lesions, i.e., Stages III and IV did not display the same marked improvement in survival. How do we explain these differences in end results? Do the poor general health and malnutrition of the patients in the indigent series alter their resistance to malignancy? Do their mistrust, suspicion, and more casual
Volume Number
100
110 3
Therapy
n
AMERICAN
m
PRIVATE
CANCER
SOCIETY
PATIENTS
1
20 IO 0 STAGE
OF
DISEASE
Fig. 3. Comparison of end results: American Cancer Society collected series versus a private hospital series. attitude account for patient delay? Does this to the development of delay contribute generally larger lesions in this group of patients even in the same International Stage reported a differof the disease? Jameson ence in outcome of treatment in New Zealanders of European descent compared to Polynesians but attributed this to delay in presenting themselves for treatment. He noted a relatively higher death rate among Polynesians in the first year after therapy. This same higher death rate during the first year post treatment was also noted by us among the impoverished group. The Polynesian’s standard of living in New Zealand and way of life are in many ways similar to that of the poor Negro in a large metropolitan area. Another factor that may be responsible for
response
variations
in cervical
cancer
393
the inferior salvage rate in the truly indigent is lack of understanding and motivation. While there is no firm statistical evidence, casual observations suggest radiation sickness is more severe in these patients and may force them to discontinue therapy prematurely. Diddle and colleagues* noted more severe reactions in a similar group of patients being irradiated for cervical carcinoma. Additionally their nutritional state render irradiation less effective. may Garcia5 reported on the poor end results in the anemic patient being treated for cervical carcinoma. Fletcher? has noted that patients with good nutritional status have a better prognosis. Although it is extremely difficult to ascertain the true nutritional state of the Cook County Hospital patients, it has been documented0 that pregnant patients in the same geographic area have a diet low in protein and iron and high in carbohydrates. The result is a high incidence of anemia and low serum-protein levels. Most of the patients served by Cook County Hospital eat “snack” foods with empty calories. This most likely caltses a chronic nutritional deficiency. Current studies are being done to investigate thB. During the past five years, in order to circumvent the problems involved in delivering a cancerocidal dose of irradiation to such impoverished individuals, the majority of Stage I and early Stage II lesions have been treated surgically at Cook C,ounty Hospital. It was anticipated that by resorting to surgical procedures our salvage: rate might be improved. It has been show1 that adequate operation or adequate radiation gives comparable end results.ll Tlx primary surgical approach in these early lesions has been a wide surgical excision (If the uterus and surrounding tissues p!us a thorough pelvic lymph node dissection as described by Louros. lo Originally, preoperative pelvic lymphangiograms were employed sporadically. The results in those patients on whom the procedure was done were equivocal as to the presence or absence of metastatic lymph nodes. The procedure did seem to help to ensure a more adstquate
394
lsaacs
Amer.
Table I. Associated preoperative complications of Stages I and II cervical cancer treated surgically. Comparison of preoperative complications between the private and clinic patients
Complication No associated complications Anemia Hypertension Kidney disease Obesity Pregnancy Heart disease Pelvic inflammatory disease Pulmonary tuberculosis Diabetes Alcoholism Drug addiction Chronic bronchitis Previous bilateral external iliac artery grafts Age range
1iigi
1ipa$~, 35 16 15 9 8 8 8 7 4 3 2 2 1
19 to 74
22
2 2
1 27 to 72
pelvic lymph node dissection. Because of this impression, pelvic lymphangiograms have been performed routinely on the last twelve private patients. A repeat roentgen examination is done before closure of the abdomen to ascertain if all of the lymph nodes have been removed. In two patients out of the twelve, the roentgenogram detected an incomplete lymph node removal. In both instances additional dissection was carried out prior to abdominal closure. Since July 1, 1965, through June 30, 1970, there were 93 radical hysterectomies performed on the gynecological tumor service at Cook County Hospital. During a somewhat longer period of time, there have been 27 cases in my private practice that were treated by radical operation. This has provided an additional opportunity to compare complications and end results in these two very different populations. The preoperative complications in the two groups are shown in Table I. Although this cannot be substantiated, these complications probably do not fully reflect the difference in the general state of health in the two groups. Postoperative complications. The post-
Table II. Comparison complications between clinic patients
June J. Obstet.
1, 1971 Gynec.
of postoperative the private and ____--
Complication No complications Bladder atony Wound infection Uterovaginal fistula Vesicovaginal fistula Wound dehiscence Pyelonephritis Lymphocyst Second operation for hemorrhage Pelvic hematoma Pelvic abscess Ileus Pulmonary embolus Sciatic nerve injury with foot drop Tumor found at edge of specimen requiring vaginectomy Radical vulvectomy and groin dissection for associated carcinoma of vulva Deaths due to surgery Postoperative days in hosuital
1
93 44 16 12 8 3 2 2 2 2 1 1 1 1 1
I-
27 12 5 4 3 1
1
3
1
6 13 to 110 11 to 37
operative complications were more numerous and severe in the Cook County Hospital patients. Table II lists the number of complications encountered in the clinic group as compared with the private series. There were six deaths in the Cook County series. Three of these deaths, namely, a death due to hypovolemia, a death of a patient who developed a uterovaginal fistula with superimposed sepsis, and a patient with an undiagnosed bowel obstruction, would probably be classified as preventable. The remaining deaths, however, should be classified as nonpreventable, and may simply be attributable to patient material, although this is philosophical. One patient died of a massive hemorrhage due to a slough of the external iliac artery; she had been discharged from the hospital on the fourteenth postoperative day in good condition. She returned thirteen days later in shock. She was taken to the operating room, and the artery was successfully repaired, but the accom-
Volume Number
Therapy
110 3
Table III.
Salvage rate of 70 patients operated upon for cervical cancer at Cook (bounty Hospital. Results of follow-up for 2 to 5 years
response
in cervical
cancer
395
Table IV. Salvage
rate of 20 patients operated upon for cervical cancer at Cook County Hospital by the author. Result> of follow-up for 2 to 5 years --____
Stape
1
variafions
‘;;,;g[ii
1-i;
I
1
Alive Dead Lost
24 17 6
58.5
Alive Dead Lost
8 10 2
44.4
22”
18 5
1
& 2
0 5 0
II
Alive Dead Lost
8
Alive Dtlad Lost
0 4 0
0
0
0
57.1
6
!”
1
4t
::
1
II
Kecurrent Alive 0 Dead 3 Lost 0 ‘One alive with disease. TTwo surgical deaths. $One
surgical
death.
$0~
surgical
death.
0 2
1
panying massive blood loss and associated sepsis proved fatal. The second patient died of a pelvic abscess. She left the hospital on the eleventh postoperative day in good condition. She returned three days later moribund. Postmortem examination revealed a huge pelvic abscess. The last patient suffered hepatic necrosis with resulting hemorrhagic diathesis and death. For twenty-four hours prior to operation (unknown to the nursing staff), she had consumed a massive quantity of alcohol. The immediate toxic effect of the ethanol, as well as prior excessive alcohol consumption, combined with the anesthesia probably produced the liver necrosis. At the time of autopsy, about 1,500 ml. of blood was found in the pleural cavity. There were also multiple kidney abscesses. The fact that she was also a heroin addict was probably contributory. The convalescence of these Cook County Hospital patients after discharge from the ward is less than ideal. Inadequate hygienic surroundings, lack of home nursing care, untimely coitus, alcohol and narcotic consumption, and ignorance all add up to the possibility of a stormy recovery.
Recurrent Alive Dead Lost
‘,4 -+
1
*One
alive
with
tone
surgical
death.
disease.
$0~
surgical
death.
The survival rates in this surgical series are far below what might have been anticipated. Of the seventy patients operated upon two to five years ago, the determinate two- to five-year survival rate in the Stage I lesions was only 58.5 per cent (Table III). A somewhat similar experience was noted with the same type of clinic material treated for recurrent carcinoma at King’s County Hospital; only 8 of 193 of their patients survived five years after therapy.* It could be suggested that such poor results would not have occurred if these Cook County women had been surgically treated by the senior attending staff rather than by residents with attending staff supervision. However, twenty of the seventy cases in the indigent series herein reported were operated upon personally by the author. The salvage rate in the Stage I lesions in this group was 57.1 per cent, a percentage virtually identical with the over-all indigent series. This is seen in Table IV. The one patient cited is preterminal. The two- to ten-year surviva1 rat<: of 18 patients in the author’s private practice was 93.7 per cent. The one patient who died of
396 lsaacs
recurrent disease did not receive postoperative irradiation even though a positive node was found. The material presented demonstrates differences in survival rates based on clinical material. I cannot explain why such a discrepancy exists but have shown only that it does exist. Perhaps well-planned prospective studies could help to discover the actual factors that account for these staggering differences. It might be worthwhile to postpone treatment in the indigent patient for a month or more. During this time they could be housed in a “diagnostic pretreatment compound.” In such an environment in addition to the usual tumor work-up, their nutritional, social, and physical state might be
REFERENCES
1.
Calame, R. J.: AMER. J. OBSTET. GYNEC. 105: 380, 1969. 2. Diddle, A. W., Davis, M., O’Connor, K. A., and Brown, B.: AMER. J. OBSTET. GYNEC. 71: 768, 1956. 3. Fletcher, G. H.: Cancer of the Uterus and Ovary, Chicago, 1969, Year Book Medical Publishers, Inc., p. 192. 4. Fletcher, G. H.: Uterine cervix, in Textbook of Radiotherapy, chap. 10, Philadelphia, 1966, Lea & Febiger, Publishers. 5. Garcia, M.: The Effect of Anemia and Uropathy on the Curability of Carcinoma of the Cervix. Read before 58th Annual Meeting, American Roentgen Ray Society, 1957. 6. Graham, J. B., Sotto, L. S. J., and Paloncek, F. P.: Carcinoma of the Cervix, Philadelphia, 1962, W. B. Saunders Company.
Amer.
June J. Obstet.
1, 1971 Gynec.
vastly improved. Good hygiene, nourishing food, isolation from the stresses of their ordinary type of existence, and patient and understanding counseling in comfortable surroundings might add more to improved salvage rates than simply an efficient medical evaluation and an immediate institution of therapy. Would this be more costly? Probably not. The average Stage IV cervical cancer patient lives about 13 months, during which time the suffering and medical expense can be astronomical. Much of this expense is born by the state, and the end result is tragedy. If this same financial expenditure could be utilized for proper pretreatment preparations, the cost might be lowered and the end result more gratifying.
7.
James, A. G.: Cancer Prognosis Manual, 1966, American Cancer Society, Inc., p. 59. 8. Tameson. M. H.: Aust. New Zeal. ”T. Obstet. “Gynaec.‘% 258, 1969. 9. Keith, L., Evenhouse, H., and Webster, A.: Obstet. Gynec. 32: 415, 1968. 10. Louros. N. Cl.: Int. T. Gvnec. Obstet. 8: 62, 1970. 11. Masubuchi, K., Tenjin, Y., Kubo, H., and Kimura, M.: AMER. J. OBSTET. GYNEC. 103: 566, 1969. 12. Rotkin, I. D., and Cameron, J. R.: Cancer 21: 663, 1968. 13. Schmitz, H. E., Geiger, C. A., Smith, C. J., and Bleichert, P. A.: Obstet. Gynec. 4: 75, 1954. ”
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I