Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery

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Abstract
BACKGROUND In the treatment of prostate carcinoma, radiotherapy and surgery are common choices of comparable efficacy; thus a realistic comparison of the potential long term sequelae, such as the risk of second malignancy, may be of relevance to treatment choice. METHODS Data regarding the rate of incidence from the Surveillance, Epidemiology, and End Results Program cancer registry (1973–1993) were used to compare directly second malignancy risks in 51,584 men with prostate carcinoma who received radiotherapy (3549 of whom developed second malignancies) with 70,539 men who underwent surgery without radiotherapy (5055 of whom developed second malignancies). Data were stratified by latency period, age at diagnosis, and site of the second malignancy. Directly comparing the risks in the radiotherapy group with those in the surgery group largely avoids problems associated with underreporting second malignancies. RESULTS Radiotherapy for prostate carcinoma was associated with a small, statistically significant increase in the risk of solid tumors (6%; P = 0.02) relative to treatment with surgery. Among patients who survived for ≥ 5 years, the increased relative risk reached 15%, and was 34% for patients surviving ≥ 10 years. The most significant contributors to the increased risk in the irradiated group were carcinomas of the bladder, rectum, and lung, and sarcomas within the treatment field. No significant increase in rates of leukemia was noted. CONCLUSIONS Radiotherapy for prostate carcinoma was associated with a statistically significant, although fairly small, enhancement in the risk of second solid tumors, particularly for long term survivors. The pattern of excess second malignancies among men treated with radiotherapy was consistent with radiobiologic principles in terms of site, dose, and latency. In absolute terms, the estimated risk of developing a radiation‐associated second malignancy was 1 in 290 for all prostate carcinoma patients treated with radiotherapy, increasing to 1 in 70 for long term survivors (≥ 10 years). Improvements in radiotherapeutic techniques, along with diagnosis at younger ages and earlier stages, are resulting in longer survival times for patients with prostate carcinoma. Because of the long latency period for radiation‐induced tumors, this may result in radiation‐related second malignancy risk becoming a more significant issue. Cancer 2000;88:398–406. © 2000 American Cancer Society.