The Surveillance, Epidemiology and End Result (SEER) Cancer Registries has assessed the risk of developing a second primary cancer in 292,029 men diagnosed with prostate cancer between 1973 and 2000. Excluding subsequent prostate cancer and adjusting for the risk of death from other causes, the cumulative incidence of a second primary cancer among all patients was 15.2% at 25 years (95% confidence interval [CI], 5.01-5.4). There was a significant risk of new malignancies (all cancers combined) among men diagnosed prior to age 50 years, no excess or deficit in men aged 50 to 59 years, and a deficit in cancer risk in all older age groups. The authors suggested that this deficit may be attributable to decreased cancer surveillance in an elderly population. Excess risks of second primary cancers included cancers of the small intestine, soft tissue, bladder, thyroid, and thymus, as well as for melanoma. Prostate cancer diagnosed in patients aged 50 years or younger was associated with an excess risk of pancreatic cancer.
The underlying etiology of developing a second primary cancer after prostate cancer may be related to various factors. Some of the observed excess risks could be associated with prior radiation therapy. Radiation therapy as the initial treatment for prostate cancer was found to increase the risk for bladder and rectal cancer as well as cancer of the soft tissues. More than 50% of the small intestine tumors were carcinoid malignancies, suggesting possible hormonal influences. The excess of pancreatic cancer may be due to mutations in BRCA2, which predisposes to both. The risk for melanoma was most pronounced in the first year of follow-up after diagnosis raising the possibility that this is the result of increased screening and surveillance.
One Swedish study using the nationwide Swedish Family Cancer Database assessed the role of family history in the risk of a second primary cancer following prostate cancer. Of 18,207 men with prostate cancer, 560 developed a second primary malignancy. Of those, the relative risk (RR) was increased for colorectal, kidney, bladder, and squamous cell skin cancers. Having a paternal family history of prostate cancer was associated with an increased risk for bladder cancer, myeloma, and squamous cell skin cancer. Among prostate cancer probands, those with a family history of colorectal cancer, bladder cancer, or chronic lymphoid leukemia were at increased risk of that specific cancer as a second primary cancer.
Risk of Other Cancers in Multiple-Case Families
Several reports have suggested an elevated risk of various other cancers among relatives within multiple-case prostate cancer families, but none of these associations have been established definitively.[25,26,27]
In a population-based Finnish study of 202 multiple-case prostate cancer families, no excess risk of all cancers combined (other than prostate cancer) was detected in 5,523 family members. Female family members had a marginal excess of gastric cancer (standardized incidence ratio [SIR] = 1.9, 95% CI, 1.0-3.2). No difference in familial cancer risk was observed when families affected by clinically aggressive prostate cancers were compared with those having nonaggressive prostate cancer. These data suggest that familial prostate cancer is a cancer site-specific disorder.