Clinical implications of family history of prostate cancer and genetic risk single nucleotide polymorphism (SNP) profiles in an active surveillance cohort.

OBJECTIVES: To explore the potential prognostic role of family history (FH) of prostate cancer and prostate cancer risk single nucleotide polymorphisms (SNPs) in patients undergoing active surveillance (AS) for prostate cancer. This is the first study to date, which has investigated the potential prognostic role of SNP profiles in an AS cohort PATIENTS AND METHODS: FH data were collected from patients in the Royal Marsden Hospital AS study. In all, 39 prostate cancer-risk SNPs identified from published genome wide association studies (GWAS) were genotyped using the Sequenom Platform and TaqMan™ assays from available DNA. The cumulative genetic-risk scores for each patient were then calculated using the weighted effect estimated from previous GWAS (log-additive model). FH status and the genetic-risk scores were assessed against adverse outcomes in AS, time to treatment and adverse histology on repeat biopsy, using univariable and multivariable Cox regression models to address time to treatment; and binary logistic regression to address biopsy upgrade. RESULTS: Of 471 patients, 55 (13.6%) had adverse histology on repeat biopsies and 145 (30.8%) had deferred treatment. On univariate analysis, there was no significant relationship between FH of prostate cancer in any degree of relation, and adverse histology or time to treatment. For risk score analyses, 386 patients' DNA was studied; and there was also no relationship found between the calculated genetic risk scores and adverse histology or time to treatment (P = 0.573 and P = 0.965, respectively). The retrospective study design and the few events were the main limitation of the study. CONCLUSIONS: There is currently insufficient data to support the use of FH status or prostate cancer SNP profile risk scores as prognostic factors in AS and these should not be used to influence management decisions. As more genetic variants are discovered this may change and should be reassessed in multicentre AS cohorts.

Medium-term outcomes of active surveillance for localised prostate cancer.

BACKGROUND: Active surveillance (AS) aims to allow men with favourable-risk, localised prostate cancer to avoid unnecessary treatment. OBJECTIVE: To describe the clinical outcomes of a prospective study of AS. DESIGN, SETTING, AND PARTICIPANTS: A single-centre, prospective cohort study. Eligibility criteria included histologically proven prostate adenocarcinoma, age 50-80 yr, stage T1/T2, prostate-specific antigen level (PSA) <15 ng/ml, Gleason score (GS) ≤ 3+3 (GS ≤ 3+4 if aged >65 yr), and percent positive biopsy cores (PPC) ≤ 50%. INTERVENTION: Patients were assessed by serum PSA level, and digital rectal examination at 3-mo intervals in year 1, 4-mo intervals in year 2, and at 6-mo intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed after 18-24 mo and every 2 yr thereafter. Treatment was recommended for PSA velocity (PSAV) >1 ng/ml per year or adverse histology, defined as GS ≥ 4+3 or PPC >50%. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes described, using Kaplan-Meier methods, were rate of adverse histology on repeat biopsy, freedom from treatment, biochemical control after deferred treatment, and overall survival. Analyses using Cox regression were performed to determine predictors of deferred treatment and adverse histology. RESULTS AND LIMITATIONS: The study enrolled 471 eligible patients from 2002 to 2011. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eighty-eight percent of patients had T1 disease and 93% had GS ≤ 3+3. At median follow-up of 5.7 yr, the 5-yr rate of adverse histology and treatment-free probability was 22% (95% confidence interval [CI], 16-29%) and 70% (95% CI, 65-75%), respectively. There were two deaths from prostate cancer. Predictors of time to adverse histology were GS 7, PSAV >1 ng/ml per year, low ratio of free PSA to total PSA, and PPC >25%. Longer follow-up is needed to confirm the safety of this strategy. CONCLUSIONS: This study demonstrates satisfactory medium-term outcomes for AS in selected men with localised prostate cancer.