Hereditary and Familial Prostate Cancer: Biologic Aggressiveness and Recurrence

Prostate Cancer

REVIEWING THE LITERATURE Prostate Cancer Hereditary and Familial Prostate Cancer: Biologic Aggressiveness and Recurrence Steven R. Potter, MD, Alan W. Partin, MD, PhD The Brady Urological Institute, The Johns Hopkins Hospital Baltimore [Rev Urol. 2000:2(1):35-36] A lthough all men are at increased risk for prostate cancer developing with increasing age, a family history of prostate cancer in a first-degree relative multiplies that risk approximately twofold. The terms “familial” and “hereditary” prostate cancer both imply increased risk but are not synonymous. Familial prostate cancer refers to a clustering of this disease within families. Hereditary prostate cancer (HPC) refers to a specific subtype of familial prostate cancer marked by a pattern consistent with passage of a susceptibility gene via Mendelian inheritance. The criterion for HPC is a family with three generations affected, three first-degree relatives affected, or two relatives affected before age 55. Approximately 43% of men with a diagnosis of prostate cancer before age 55 have HPC. While men with HPC are at increased risk for prostate cancer development at an early age, biologic behavior of these cancers remains unclear. Numerous investigators have attempted to determine the biologic aggressiveness and risk of recurrence of hereditary and familial prostate cancer after definitive therapy. Family History of Prostate Cancer in Patients With Localized Prostate Cancer: An Independent Predictor of Treatment Outcome Kupelian PA, Kupelian VA, Witte JS, et al. J Clin Oncol. 1997;15:1478-1480. Kupelian and associates used a cohort of 1,038 men treated for prostate cancer with either radiation therapy (RT) or radical prostatectomy (RP) to evaluate treatment outcome in men with familial and sporadic prostate cancer. Patients reporting prostate cancer in a first-degree relative when questioned at presentation were classified as having a positive family history of prostate cancer. A total of 455 men who underwent RP and 583 who underwent RT formed the cohort for analysis. These men were followed with prostate- specific antigen (PSA) testing for evidence of disease recurrence for a median of 26 months. Biochemical (PSA) recurrence was defined as a single detectable (more than 0.2 ng/mL) PSA level (RP patients) or as two consecutive increasing PSA levels after a nadir PSA level (RT patients). Kupelian and colleagues reported 3-year rates of freedom from biochemical (PSA) recurrence of 52% and 72% in men with and without a family history of prostate cancer, respectively. The 5-year rates of biochemical freedom from recurrence were 52% for men without a family history of prostate cancer and 29% for men with such a history. Kupelian and associates then stratified these men into a favorable group (PSA less than 10 ng/mL, biopsy Gleason score less than 7, and clinical stage T1-2) and an unfavorable group (all other cases) to assess further the impact of family history on the likelihood of prostate cancer recurrence. In the favorable group at 5 years, biochemical recurrence-free survival was noted in 80% of men with a negative family history but only 49% of those with a positive history. In the unfavorable group, biochemical freedom from recurrence was seen in 35% of men with a negative and 20% of men with a positive family history. Kupelian and associates were the first to demonstrate a significant difference in treatment outcome in men with a familial history of prostate cancer relative to those with sporadic prostate cancer. These findings suggest that familial prostate cancer (which, in this study, included both familial and the much less common hereditary cancers) is more biologically aggressive than sporadic cancer. This apparent increased aggressiveness seems independent of Gleason score or clinical stage and raises the possibility that underlying molecular differences exist between sporadic and familial variants of prostate cancer. The obvious implication of these results is that family history may be useful in estimating the potential benefits of therapy with curative intent and, thus, as an element of decision-making regarding selection of men for such therapy. continued on next page WINTER 2000 REVIEWS IN UROLOGY 35 Prostate Cancer continued Biological Aggressiveness of Hereditary Prostate Cancer: Long–term Evaluation Following Radical Prostatectomy Bova GS, Partin AW, Isaacs SD, et al. J Urol. 1998;160:660-663. Bova and associates attempted to answer the question raised by Kupelian et al of whether familial and sporadic prostate cancers differed in biologic aggressiveness by assessing biochemical recurrence rates in long-term followup after RP. These authors first examined a cohort of men who underwent RP at a single institution, 94 of whom had familial prostate cancer and 562 of whom had sporadic prostate cancer. They then evaluated a group of 52 men meeting the strict criteria for HPC by matching these men for pathologic Gleason score and pathologic stage with men undergoing RP during the same time interval at the same institution. Bova and colleagues found that the 94 men with familial prostate cancer had the same likelihood of biochemical (PSA) freedom from prostate cancer recurrence as the 562 men with sporadic prostate cancer serving as probands. The 52 men with HPC and their matched controls were followed for a mean of 61 and 65 months, respectively. No significant difference in the likelihood of freedom from biochemical (PSA) recurrence was seen in these groups. These observations suggest that no significant difference in biologic aggressiveness exists between sporadic and hereditary prostate cancer and that men with familial or hereditary prostate cancer could thus receive the same therapy as men with sporadic cancer, with the same expectation of cure. No Difference in Survival Between Sporadic, Familial and Hereditary Prostate Cancer Gronberg H, Damber L, Tavelin B, Damber JE. Br J Urol. 1998;82:564-567. Gronberg and colleagues evaluated a population-based cohort of men in an attempt to compare the survival of men with familial and hereditary prostate cancer with that of men who had sporadic prostate cancer. They examined a cohort of 5,402 men with a diagnosis of prostate cancer who were recorded in the Swedish Cancer Register between 1959 and 1963. Of these men, 249 had at least one son with a diagnosis of prostate cancer. The 2,667 fathers with sons without prostate cancer were considered sporadic cases. The cohort of sons was then stratified into families with HPC (three or more cases per family) and familial prostate cancer (two cases of cancer per family). Each of these affected 36 REVIEWS IN UROLOGY WINTER 2000 sons was matched with five reference prostate cancer patients selected randomly from the Swedish Cancer Register and matched for age at cancer diagnosis and year of diagnosis. The authors calculated both overall and cancer-specific survival. No significant differences in either overall or cause-specific survival were found between sporadic, familial, and hereditary prostate cancer patients. Clinical and pathologic stages were unavailable for analysis, but the presenting tumor grade for familial and hereditary prostate cancer patients did not differ significantly from a population-based cohort of men with sporadic prostate cancer. The authors concluded that treatment plans should not differ for men based on the presence or absence of familial prostate cancer. These findings were consistent with those of Bova and colleagues in finding no inherent difference in the behavior of familial prostate cancers. Patterns of Inheritance and Outcome in Patients Treated With External Beam Radiation for Prostate Cancer Hanlon Al, Hanks GE. Urology. 1998;52:735-738. Hanlon and Hanks evaluated retrospectively the biochemical (PSA) outcomes after RT in men with hereditary and familial prostate cancer compared with men treated with RT for sporadic prostate cancer. The cohort evaluated received RT without hormonal therapy over a 10-year period and consisted of 823 men without a family history of prostate cancer, 78 men who met the criteria for familial prostate cancer, and 19 men with HPC. Median follow-up was 25 months for the entire cohort. The investigators defined biochemical recurrence as two consecutive rising PSA levels exceeding 1.5 ng/mL. The patients with hereditary and familial prostate cancer were combined into a single grouping of 97 men with a family history of prostate cancer and were compared with 194 patients with sporadic prostate cancer culled from the above cohort and matched for age at diagnosis, pretreatment PSA level, and clinical stage. Hanlon and Hanks found no significant difference in biochemical failure rates between carefully matched men with and without a family history of prostate cancer. These results were consistent with those of Bova and colleagues and Gronberg and associates in finding no evidence of increased biologic aggressiveness or increased risk of failure after definitive therapy for clinically localized prostate cancer in men with either hereditary or familial prostate cancer. ■