Long-term follow-up observations in cervical cancer.

During the period 1935–1954 a total of 394 patients with primary cervical cancer were examined with a view toward treatment. Ten of that number were diagnosed as having carcinoma in situ. Treatment was omitted for specific reasons in 10 of the patients with invasive cancer. A 5 to 20 year follow-up is reported for the remaining 375 patients treated primarily by irradiation. That consecutive series of cases can be divided into two groups of approximate equal number at the end of year 1949. The effectiveness of treatment is tested by comparing relative 5 year results for the more recently treated patients with those applying to the earlier group. Advance in survival is not demonstrated despite the fact that the percentage distribution of early lesions increased during the years in question. The difference in results is investigated by tabulating data in accumulative survival rates. At 5 years' observation those values do not differ from relative results because all of the patients are observed for that number of years. The accumulative rates present a more valid assessment, however, by showing the rate of accumulated deaths from cancer as well as from other causes. The lesser survival rate patients treated in the 1950–1954 period is explained by a greater loss due to causes other than cancer and by a disproportionate incidence of cases with an unfavorable prognosis. The less favorable material is recognized by more rapidly accumulated cancer deaths during the first year of observation. Those patients are found among the Stage II cases treated in 1952 and in 1953. At more than 5 years' observation the accumulative survival rate falls below the corresponding relative value. The number of patients changes by decrease in the number not yet followed for specified periods. The accumulative survival rate falls below relative values by the weight of difference in early results upon all subsequent time intervals. Deaths from cancer accumulate rapidly for the first 2 years following treatment. A realistic majority is reached by the fifth year, but there is, in this series, a gradual accumulation through the eleventh year. A satisfactory statement of results can be made, therefore, on the basis of 5 year values. A patient clinically well but lost to follow-up after that period has low probability of dying from cancer. The risk appears almost eliminated after the tenth year. In the observations here reported the accumulative loss to follow-up does not reach significant proportions until after the ninth year. The deaths due to intercurrent conditions also accumulate slowly, but continue to expand for the total period of observation. A significant number of these are due to the development of second primary cancers. Three occurred in the rectum and one in the endometrium. Consideration is given the possibility that the previous irradiation may be an etiological factor. Experience with programs of secondary irradiation has been unfavorable in the treatment of patients with persistent or reappearing cancer. In more than 50 such attempts only 2 patients have survived an additional 5 years after the second course of therapy. Pelvic exenteration is more effective, but in 5 of the 9 attempts at operation the disease was found too advanced. The spread of cancer is believed assessable in 123 of the 132 deaths from cancer in Stages I, II, and III. Half of that number were in patients with distant metastases with or without local disease in the pelvis. The most common sites of involvement are lung and bone. The incidence of distant spread is greatest in Stage I, which shows a rate of 66 per cent. The effectiveness of treatment is assessed in relation to complications. Two examples are reported of very late injury attributed to radiation. Among major complications the incidence of fistula is believed to have identity with significant changes in radium treatment. The rate falls from 11 per cent in the earliest years of the report to only 2 per cent in the 1950–1954 period. This improvement is taken as evidence of advance in treatment, despite the lack of increased survival rates for the most recent years. A statement of relative survival has weakness if used alone to compare results. The fall in survival rate for the 1950–1954 period is satisfactorily explained in accumulative tables, but it is possible that treatment is also a factor. During those years experience was accumulated in the use of specific applicators for radium treatment. There is more than speculative reason to suspect overexposure. Whatever the cause of failure there is evidence of recovery from those defects at the end of the 1950–1954 period. Additional exploration by dosimetry studies is intended as a supplement to this report.