Clinical investigation
Prostate
Second malignancies after prostate brachytherapy: Incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up

https://doi.org/10.1016/j.ijrobp.2006.05.016Get rights and content

Purpose: To report the incidence of second bladder and colorectal cancers after prostate brachytherapy.

Methods and Materials: This review included 125 patients treated with I-125 brachytherapy alone, and 223 patients who received supplemental external beam radiation therapy. Median follow-up was 10.5 years. Patients were followed for the development of lower genitourinary and colorectal cancers. Second malignancies arising five years after radiation therapy were defined as being potentially associated with treatment; observed rates were then compared with age-matched expected rates according to Surveillance, Epidemiology, and End Results data.

Results: Five years out of treatment, there were 15 patients with a second solid tumor, including bladder cancer (n = 11), colorectal cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second malignancy was no different in patients treated with brachytherapy alone (1.6%) vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were more observed bladder cancers compared with those expected (relative risk, 2.34, 95% confidence interval 0.96–3.72; absolute excess risk 35 cancers per 10,000 patients). Relative risk did not significantly change over increasing follow-up intervals up to 20 years after treatment.

Conclusions: There may be an increased but small risk of developing a second malignancy after radiation therapy for prostate cancer. This outcome could be related to radiation carcinogenesis, but more vigilant screening and thorough workup as a result of radiation side effects and predisposing conditions (e.g., genetic and environmental factors) in many of the patients found to have second malignancies likely contributed to the higher number of observed malignancies than expected.

Introduction

Because of a trend toward diagnosing prostate cancer at a younger age and earlier stage (1, 2) and increasingly successful treatment options, (3) the number of prostate cancer survivors is expected to continue to rise. The success of radiation therapy (RT) has been an important factor in increasing rates of survivorship, but one legitimate long-term concern may be radiation-associated malignancies, particularly secondary solid tumors (4). Some estimates of second malignancy after RT for prostate cancer include a small but statistically significant added risk of second bladder cancers (5, 6) and colorectal cancers (5, 7, 8) in patients with long follow-up. One critical factor in the development of secondary cancers appears to be the volume of tissue that is radiated above a threshold dose (9). However, because estimates of the risk of second malignancy after RT are often generated from large datasets that lack the technical details of treatment to obtain sufficient statistical power, risk cannot be easily described according to the volume radiated. The goal of this study is to report the rate of bladder and colorectal cancers in patients with 15 years of potential follow-up who were treated with brachytherapy for prostate cancer, with or without supplemental external beam radiation therapy.

Section snippets

Methods and materials

This review included 348 patients with biopsy-proven adenocarcinoma of the prostate who were treated with prostate brachytherapy at the Seattle Prostate Institute from January 1987 to January 1994. Two subsets of patients included: 125 consecutive patients treated with an Iodine-125 (I-125) implant as monotherapy between 1988 and 1990 (10) and 223 consecutive patients treated with external beam RT followed by an I-125 or Palladium-103 implant between 1987 and 1994 (11). Patient characteristics

Results

Overall, 15 of 348 patients (4.3%) developed a bladder (n = 11), colorectal (n = 3), or prostatic urethra (n = 1) carcinoma five or more years after RT (median time, 9 years 6 months), at a median age of 80 years. Thirteen of 223 patients who received supplemental RT (5.8%) developed a bladder or colorectal malignancy compared with 2 of 125 patients who received brachytherapy alone (1.6%, p = 0.0623). Details of each potential radiation-associated secondary solid tumor are listed in Table 2.

Discussion

Over the last decade, treatment for prostate cancer has become increasingly successful, in no small part related to earlier diagnosis with PSA screening. RT has led to high rates of curability for all stages of disease (10, 11, 17, 18), with dose, volume treated, and use of hormonal therapy tailored to the risk level of the patient. With control rates and survivorship that approach 100% in some large series (19, 20, 21), long-term complications become an increasingly important factor for the

Conclusions

The incidence of developing a secondary bladder cancer five or more years after brachytherapy, with or without supplemental external beam RT, was slightly higher (absolute excess risk 35 bladder cancers per 10,000 patients) than age-matched SEER data indicates. Patients should be followed after successful treatment for prostate cancer with the understanding that there may be a small risk of developing a second solid tumor that is radiation-associated, especially in long-term survivors.

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