LIFE EXPECTANCY AND INCIDENCE OF MALIGNANT DISEASE

LIFE EXPECTANCY AND INCIDENCE OF MALIGNANT DISEASE IRA T. NATHANSON,' M.S., M.D., AND CLAUDE E. WELCH,2 M.A., M.D. (From the Collis P. Huntington Memorial Hospital, Harvard University, Boston, Mass., and the Pondville Hospital, Wrentham, Mass.) This is the third in a series of articles concerned with the life expectancy of patients with malignant disease. In this instance cancer of the gastrointestinal tract will be considered. The only carcinomas of this type observed at the Collis P. Huntington and Pondville Hospitals in sufficient numbers to be of statistical significance are those of the esophagus, stomach, and rectum. The method of analysis of the data has been described previously (1, 2) ; all records have been reviewed personally. The date of onset of the disease has been taken from the first symptom directly referable to the lesion or the first significant change in symptoms which have existed for a number of years. All patients entering the hospitals in the years 1912-1933 are included except a few in whom a definite history of onset could not be ascertained or the diagnosis of malignant disease could not be determined beyond doubt. Carcinoma of the esophagus is at the present time the most fatal of all types of neoplasm. Dysphagia, which is usually the first symptom, frequently appears only after the disease is far-advanced and not amenable to treatment. Nevertheless, a few cures by radical surgery or irradiation have been reported. Torek (3) in 1925 described a case in which the patient had survived for 11 years following radical resection. More recently G. G. Turner (4) and others have reported successful extirpations. Apparent cures from irradiation have been obtained by Guisez (S), who cited 3 patients free from symptoms for 11, 10, and 5 years, and Baum (6), whose patient was living 7 years after onset. The life expectancy, once the disease is recognized, is short, since the small diameter of the esophagus and the thin muscular wall contribute to occlusion of the lumen or perforation. Except in unusual instances all that can be offered the patient is palliative therapy. Simple gastrostomy and mechanical dilatation with bougies have been employed frequently. Implantation of radon seeds and external irradiation have been used singly or in combination with the other methods of treatment. In recent years enormous doses of high-voltage x-rays have been given without materially influencing the course of the disease except in the instances recorded above. There are 297 cases of cancer of the esophagus included in this survey. Lucius N. Littauer Fellow in Cancer. Resident Surgeon, Massachusetts General Hospital. 457

458 IRA T. NATHANSON AND CLAUDE E. WELCH In order to appraise the results of the various forms of treatment we have divided the cases into untreated (83 cases), those treated with gastrostomy alone (37 cases), those having gastrostomy plus some form of irradiation, usually x-ray (37 cases), and those treated by irradiation, either alone or combined with dilatation by bougies (138 cases). In 2 cases resection was attempted, but both patients died. Eleven cases (3.7 per cent) are listed as not traced, having been followed less than a year from onset. Untreated Cases: Of the 83 untreated patients, 25 per cent were dead in 5 months, 50 per cent in 7 months, 75 per cent in a year after the appearance of the first symptom. Only 3 patients lived over 2 years; the longest duration was 3.5 years. The average duration of life after onset, 9.5 months, is slightly longer than the median duration. The duration is definitely longer if the carcinoma originates above the suprasternal notch. Per cent Gaetrostomy only ( 83 cases) - (u8 )--- Data on untreated carcinoma of the esophagus have been collected by the British Ministry of Health. Greenwood (7) studied 299 cases and found that 25 per cent of the patients were dead in 6 months, 50 per cent in 8 months, and 75 per cent in a year, while the average duration was 12 months. In a later report (8) the average duration in 57 additional cases is given as 6.2 months. Gastrostomy: Gastrostomy serves to prevent death by starvation only to permit the patient to die of some other complication, such as perforation or pneumonia. It does significantly increase length of life, but this gain is only a matter of a few months, and the decision as to its value must be made on the individual case. Of the 37 patients in whom gastrostomy was performed without any other treatment, 25 per cent were dead in 8 months, 50 per cent in 10 months, and 75 per cent in 18 months. The last patient died 3 years after the onset of the

LIFE EXPECTANCY AND INCIDENCE OF MALIGNANT DISEASE 459 disease. The median age of the group was 59. The increased length of life afforded the median patient by gastrostomy is 3 months, or about 40 per cent over the life expectancy in the untreated case. This is essentially in accord with the results found by the British Ministry of Health (8), in which it was noted that an increase of 1.9 months of life (31 per cent) was obtained in the average patient by gastrostomy. Radiation: It will be seen in Fig. 1 that patients who have been irradiated live longer than those who have had no treatment but not so long as those treated by gastrostomy alone. A combination of the two methods seems to give a life expectancy intermediate between the two groups. This may mean that radiation contributes to the ease of perforation or to cachexia, but our cases are too few to prove that there is a statistically significant variation in length of life depending upon the type of treatment. Histologically carcinoma of the esophagus, which is nearly always of the squamous-cell type, resembles carcinoma of the lip or cervix. It should, therefore, be susceptible to radiation. However, the esophagus differs from these organs in that it is a hollow viscus and has a thin wall so that with regression of the disease perforation may occur readily. It may be that radiation can in the future be increased in effectiveness by allowing more gradual regression with the production of enough fibrous tissue to prevent perforation. Among the 138 patients treated by irradiation alone, 25 per cent were dead in 7 months, 50 per cent in 10 months, 75 per cent in 14 months. One lived 3.5 years. The median age was 57. In 37 cases radiation therapy was supplemented by gastrostomy. The increase in life expectancy at the quartiles and median is a fraction of a month greater than that with radiation alone and a fraction of a month less than with gastrostomy alone. The median age was 58. One patient lived 2.3 years after onset of the cancer. Sex and Life Expectancy: Reference to Fig. 3 will show the variation in life expectancy dependent upon sex. The general life expectancy curve includes both the treated and untreated cases. The median length of life for the entire group is 0.83 years. The median life expectancy for females alone is 0.93 years, and for males alone is 0.81 years. The life expectancy with carcinoma of the esophagus is slightly greater in the female than in the male for the first year after onset; thereafter the interval decreases, so that from 18 months onward the prognosis is the same. It appears that the females have a slightly better prognosis than the males. Age and Sex Distribution: Eighteen per cent of the total of 334 patients were females. The median age of the entire group was 58 years; the median age of the females, 57. The youngest patient was 31 years of age and the oldest 82. In approximately a third of the patients the onset of the disease was below the age 55, a third occurred in the decade thereafter, and the final third after 65. The statistics agree quite closely with those of Pack and Le- Fevre (9)) who noted that the average age was 57 at onset and that 19.5 per cent of the patients were females. Forty-five per cent of all their patients were between fifty-five and fifty-nine years of age. In a study of 1000 cases from the Mayo clinic (10) Vinson found that 16.2 per cent occurred in females, with the highest incidence between the ages of 50 and 60.

460 IRA T. NATHANSON AND CLAUDE E. WELCH Since practically all cases in this series represent recurrences after surgery or lesions too far advanced for treatment, the data presented on carcinoma of the stomach may suggest a somewhat more pessimistic outlook than would a similar series from a large general hospital. The difference, however, as will be shown later, is not a large one. There were 315 cases of carcinoma of the stomach observed in 1912-1933. The true incidence of this disease in the community at large is not indicated by this small figure, as there is a large number of cases which never reach a hospital. It would be expected that the most favorable of the cases would be the ones that would be sent to the hospital for treatment. Yet our series includes Pep cent 159 cases that had no treatment whatsoever, usually because they were considered inoperable at entry. The remaining 156 were treated in various ways. Untreated Cases: The data presented here indicate that 25 per cent of the patients were dead in 8 months, 50 per cent in 13 months, 75 per cent in 17 months after the onset of the first symptom. Thereafter the curve drops less sharply. Two patients lived over 4 years, the last dying 4.5 years after onset. The median age was 59. The similarity of the curve to that of untreated cases of carcinoma of the rectum is quite striking, for the median length of life is nearly the same in the two diseases. The average duration of life in this instance is the same as the median. Twenty-six per cent of the patients were females. The average duration of life after onset in 288 cases of untreated cancer of the stomach collected by the British Ministry of Health (8) was 12.2

months, the median 8.1 months. According to another report (7) from the same source the average duration in 134 cases was 16.8 months, and the median approximately 13. There were 46 cases in the series here reported in which simple exploratory laparotomy was done. These were not included in the untreated group, because the high mortality following exploration would reduce the length of life of the average patient. Parsons ( ll), studying cases from the Massachusetts General Hospital, found the operative mortality following laparotomy alone for cancer of the stomach to be 27 per cent. In our 46 cases that had exploration alone, the median length of life was 11 months, slightly less than that in patients who were unexplored and untreated. One patient lived 7.2 years from onset of the disease, and another 4.1 years. All the others died within 4 years. The British Ministry of Health included cases with exploratory laparotomy in their untreated group, but it appears that such cases should really be excluded from an untreated series, because of the poorer prognosis. Treated Cases: Numerous forms of treatment were employed, including gastric resection, gastro-enterostomy, both anterior and posterior, x-ray, irradiation, gastrostomy, jejunostomy, and radium. Of these methods the only ones used in an adequate number of cases for appraisal of the results statistically were resection and gastro-enterostomy. The life expectancy of the 156 treated patients is shown in Fig. 2. Twenty-five per cent of the patients were dead in 8 months, 50 per cent in 15 months, and 75 per cent in 30 months. Comparison with the curve of untreated cases shows but little gain during the first year, while thereafter the curves diverge rapidly. The life expectancy of females appears to be slightly

462 IRA T. NATHANSON AND CLAUDE E. WELCH better than that of males. The median length of life for males is 15 months; for females 19 months (Fig. 3). Life expectancy is increased moderately by gastro-enterostomy : 2 5 per cent of the patients were dead in 11 months, 50 per cent in 19 months, and 75 per cent in 30 months. Thus the length of life of the median patient was increased 8 months by this operation. Finsterer (12) found that gastro-enterostomy increased the length of life of his patients only 2.5 months. Twenty-four patients were treated by resection. Of these 25 per cent were dead in 18 months, 50 per cent in 30 months, and 75 per cent in 48 months. Four patients lived over 5 years from onset, but 3 of them died during the following year. One patient was living 13.5 years after onset. Per cent Discussion: Various clinics report widely divergent statistics of survivals in carcinoma of the stomach. The Mayo clinic (13) obtained 50 per cent three-year and 20 per cent five-year cures in cases in which resection could be performed. On the other hand, Bloodgood (14) found only 4 cures of carcinoma of the stomach in the literature up to 1915 and Lahey's figures (15) show only 3 patients living more than five years in a series of 168 cases admitted to the clinic. In Gatewood's series (16) 17 patients (4.1 per cent) out of 417 survived a five-year period. Lewisohn and Mage (17)' in a review of 647 cases, found that exploration was advisable in only 285 patients. Among this number radical resection was possible in 93 instances. Of the entire group, 8 (1.2 per cent) were living 5 years after operation. This represents 8.6 per cent five-year survivals in the resected group. Crile (18) studied 726 patients admitted to the Cleveland Clinic and found only 7 alive five years later, or 1 per cent of the entire number. Parsons' series of 233 cases from the Massachusetts General Hospital ad-

mitted in the years 1922-1926 can be compared with the one recorded in this paper. Thirty-seven cases were considered operable and in all gastric resection was done. Of the operable group, 9 (24.3 per cent) survived 5 years after operation. This means that only 4 per cent of the entire group were alive 5 years after operation. In our series there were 6 per cent alive five years after onset, but only 2 per cent alive six years after onset. Since the average delay to treatment was about 6 months, 5.5 years after onset there were 4 per cent alive. It thus appears that the general curve representing the life expectancy in both series is approximately the same. Age and Sex Incidence: Of 378 patients admitted before 1936 77 per cent were males, which compares with 79 per cent reported by Balfour (19), 72 FIG. 5 ---- patients below 45. -- = 45 to 70.... a. = over 70 per cent by Kaufmann (20), and 69.2 per cent by Pack and LeFevre (9). The median age was 55. Five cases occurred at the age of 30 or under. Approximately a third of our patients were below the age of 50, a third from 50 to 60, and the remainder older. CARCINOMA OF THE RECTUM There were 587 cases of cancer of the rectum observed before 1933. Of this group, 77 were untreated while 510 had either radical resection, colostomy, or radiation. Since the Huntington and Pondville Hospitals care for the more advanced cases of carcinoma of the rectum in this community, it is probable that the life expectancy curve is poorer than it would be in a general hospital to which more favorable cases are directed. It seems likely, however, that the prognosis of cancer of the rectum in the community at large is fairly accurately represented by these curves. The same data have been employed by Daland

464 IRA T. NATHANSON AND CLAUDE E. WELCH Pep cent 100 80 70 60 50 4 0 30 'O mr q the Wrn 1 Age -45-70 30 ---- \ \ (335 caees) Yrs. 1 2 3 4 5 6 7 8 and the authors (21) in a comparison of untreated cancers of the rectum with those treated either by resection, colostomy, or x-ray. Treated Cases: The life expectancy of all treated patients is shown in Fig. 4. It will be seen that the median length of life is 23 months; 25 per cent of the patients were dead in 13 months, and 75 per cent in 40 months. Five years after onset 89 per cent were dead, and at 10 years 97 per cent. The median age was 58. The curve of untreated cases is taken directly from the paper of Daland and the authors. The median length of life was 14

months. Treatment, then, in the median case, prolongs life 9 months. This, as has been shown before, is due to gains from resection, since neither colostomy nor radiation add to the duration of life. The operative mortality of colostomy is between 10 and 12.5 per cent, which accounts for the fact that untreated patients apparently live as long as patients with colostomy, when the group is considered as a whole. If a patient survives colostomy, however, he will live, on the average, 2 months longer than if he had had no treatment. Age and Life Expectancy: The treated cancers of the rectum have been divided into three groups. There were 99 patients less than 45 years of age, 335 from 45 to 60, and 76 over that age. The life expectancies of these three groups are shown in Fig. 5. There is no variation in these groups below the fourth year after onset; thereafter the curve of the oldest age group begins to drop sharply, while the others continue together. Age does not play a significant part in the determination of the life expectancy of patients with cancer of the rectum. If, however, the normal expectancy of life is compared with the expectancy of the patient with cancer of the rectum in various age groups, as shown in Fig. 6, and calculations are made according to the method previously outlined for cancer of the lip (2), it will be seen that carcinoma of the rectum is more malignant in the young. Ratio Dead with Cancer of the Rectum Compared with Normal Death Rate Age 2 years after onset 4 years after onset 6 years after onset Below 45... 16.0 45-70... 8.2 Above 70... 3.3 Sex and Life Expectancy: Cancer of the rectum has been considered to be more benign in females because the ratio of operability is higher since the presence of the uterus prevents the early invasion of the bladder. In Fig. 3 it will be seen that the median length of life of treated males was 2 1 months, of treated females 26 months. The difference between the two sexes becomes even more marked in later years. After five years from onset the percentage of females alive is approximately twice the figure for males. This suggests that the absolute curability is higher in the female. Sex and Age Incidence: Of a total of 656 patients, 244 (37.2 per cent) were females. A third of the cases occurred below the age of 55, a third in the ensuing decade, and the final third thereafter. The median age was 59. There were 39.3 per cent females in Pack and LeFevre's series (9). 1. The life expectancy for untreated cancer of the esophagus, in the median case, is 7 months, for cancer of the stomach 13, and for cancer of the rectum 14 months after the onset of the first symptom directly referable to the disease. 2. Five years after onset of the disease approximately 6 per cent of all patients with cancer of the stomach are alive; at the same time 11 per cent of all patients with cancer of the rectum are alive, and all patients with cancer of the esophagus are dead.

466 IRA T. NATHANSON AND CLAUDE E. WELCH 3. The median length of life of patients with carcinoma of the esophagus who have been treated by gastrostomy alone is 10.4 months after onset of symptoms; of those treated by radiation alone, 9.3 months. 4. Patients who had an exploratory laparotomy for cancer of the stomach survived, on the average, a shorter length of time after onset of symptoms than those who had no treatment at all. 5. The median life expectancy of all patients with treated cancer of the stomach in this series is 15 months. 6. The age of the patient has no influence upon the life expectancy in carcinoma of the rectum, but comparison with the normal life expectancy at varying ages shows the disease to be more malignant in the young. 7. There is an indication that the female has a slightly better prognosis than the male in carcinoma of the esophagus, stomach, and rectum. 8. Data on sex and age incidence are included. BIBLIOGRAPHY 1. NATHANSON, I. T., AND WELCH, C. E.: Am. J. Cancer 28: 40, 1936. 2. WELCH, C. E., AND NATHANSON, I. T. : Am. J. Cancer 31 : 238, 1937. 3. TOREK, F.: Arch. Surg. 12: 232, 1926. 4. TURNER, G. G.: Lancet 1 : 67, 130, 1936. 5. GUISEZ, J.: Bull. et mcm. Soc. de chir. de Paris 28: 116, 1936. 6. BAUM, S. M.: Radiology 27: 58, 1936. 7. GREENWOOD, MAJOR: Natural Duration of Cancer, British Ministry of Health Reports on Public Health and Medical Subjects, No. 33, 1926, H. M. Stationery Office, London. 8. FORBER, JANET E.: Incurable Cancer, British Ministry of Health Reports on Public Health and Medical Subjects, No. 66, 1931. 9. PACK, c. T., AND LEFEVRE, R. G.: J. Cancer Res. 14: 167, 1930. 10. VINSON, P. P.: Proc. Staff Meetings, Mayo Clinic 8: 370, 1933. 11. PARSONS, L.: New England J. Med. 209: 1096, 1933. 12. FINSTERER, H.: Wien. med. Wchnschr. 85: 1273, 1935 and ff. 13. BALFOUR, D. C.: Surg. Gynec. & Obst. 54: 312, 1932. 14. BLOODGOOD, J. C.: Surg., Gynec. & Obst. 47: 216, 1928. 15. LAHEY, F. H., AND JORDAN, S. M. : New England J. Med. 210: 59, 1934. 16. GATEWOOD: Surg., Gynec. & Obst. 56: 442, 1933. 17. LEWISOHN, R., AND MACE, S.: Surg., Gynec. & Obst. 60: 467, 1935. 18. CRILE, G. W.: Surg., Gynec. & Obst. 56: 417, 1933. 19. EUSTERMAN, G. B., AND BALFOUR, D. C.: The Stomach and Duodenum, W. B. Saunders Co., Philadelphia, 1935. 20. KAUFMANN, E.: Lehrbuch der spez. path. Anat., Walter de Gruyter & Co., Berlin and Leipzig, Ed. 9 and 10, Vol. 1, 1931, pp. 648-649. 21. DALAND, E. M., WELCH, C. E., AND NATHANSON, I. T.: New England J. Med. 214: 451, 1935.