The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over $6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log 2 HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log 2 HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.

OBJECTIVETo assess the perioperative complications and early oncological results in a comparative study matching open radical retropubic (RRP) and robot‐assisted radical prostatectomy (RARP) groups.PATIENTS AND METHODSFrom August 2002 to December 2005 we identified 294 patients undergoing RARP for clinically localized prostate cancer. A comparison RRP group of 588 patients from the same period was matched 2:1 for surgical year, age, preoperative prostate‐specific antigen level, clinical stage and biopsy Gleason grade. Perioperative complications were compared. Patients completed a standardized quality‐of‐life questionnaire. Pathological features were assessed and Kaplan‐Meier estimates of biochemical progression‐free survival (PFS) were compared.RESULTSThere was no significant difference in overall perioperative complications between the RARP and RRP groups (8.0% vs 4.8%, P = 0.064). Wound herniation was more common after RARP (1.0% vs none, P = 0.038), and development of bladder neck contracture was more common after RRP (1.2% vs 4.6%; P < 0.018). The hospital stay was less after RARP (29.3% vs 19.4%, P = 0.004, for a stay of 1 day). At the 1‐year follow‐up there was no significant difference in continence (RARP 91.8%, RRP 93.7%, P = 0.344) or potency (RARP 70.0%, RRP 62.8%, P = 0.081) rates. The biochemical PFS was no different between treatments at 3 years (RARP 92.4%, RRP 92.2%; P = 0.69).CONCLUSIONThere was no significant difference in overall early complication, long‐term continence or potency rates between the RARP and RRP techniques. Furthermore, early oncological outcomes were similar, with equivalent margin positivity and PFS between the groups.

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BACKGROUND:The long-term survival of patients with high-risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen-deprivation therapy (ADT). METHODS: In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate-specific antigen (PSA) level 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification T3. The median follow-up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer-specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk-regression model. RESULTS:The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P ¼ .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P ¼ .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P ¼ .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P ¼ .0002). CONCLUSIONS: RRP alone and EBRT plus ADT provided similar long-term cancer control for patients with high-risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality-of-life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011;117:2883-

Summary Background HSD3B1(1245A>C) has been mechanistically linked to castration-resistant prostate cancer by encoding an altered enzyme that augments dihydrotestosterone synthesis. We hypothesized that men inheriting the HSD3B1(1245C) allele would exhibit resistance to androgen deprivation therapy (ADT). Methods We determined HSD3B1 genotype retrospectively in men treated with ADT for post-prostatectomy biochemical failure and correlated genotype with long-term clinical outcomes. Patients who received postoperative adjuvant or salvage radiotherapy were eligible, provided they had residual active disease as reflected by continued increase in their PSA after treatment. We analyzed progression-free survival (PFS; primary endpoint), distant metastasis-free survival (DMFS), and overall survival (OS) according to HSD3B1 genotype. Multivariable analyses were performed to assess the independent predictive value of HSD3B1 genotype on outcomes. Results were externally validated in two additional cohorts, including a second post-prostatectomy biochemical failure cohort as well as a metastatic cohort. There was no age limit for eligibility in the primary or validation cohorts. Findings The study included 443 patients: 118 in the primary cohort, 137 in the post-prostatectomy validation cohort, and 188 in the metastatic validation cohort. In the primary study cohort, median PFS diminished as a function of the number of variant alleles inherited: 6.6 years in homozygous wild-type men (95% CI, 3.8 to not reached); 4.1 years in heterozygotes (95% CI, 3.0 to 5.5); and 2.5 years in homozygous variant men (95% CI, 0.7 to not reached); P=0.011. Median DMFS likewise decreased according to the number of variant alleles inherited: 9.1 years (95% CI, 7.4 to not reached); 6.8 years (95% CI, 4.3 to 7.4); and 3.6 years (95% CI, 1.0 to 7.3), respectively; P=0.014. Finally, OS diminished with the number of variant alleles inherited: 5-year and 10-year OS 82% (95% CI, 69 to 94) and 55% (95% CI, 35 to 75) in homozygous wild-type men; 74% (95% CI, 62 to 85) and 35% (95% CI, 21 to 49) in heterozygotes; and 58% (95% CI, 30 to 86) and 0% in homozygous variant men; P=0.0064. On multivariable analysis, the hazard ratio (HR) for progression was 1.6 for men with at least one variant allele (95% CI, 1.0 to 2.7; P=0.074), which compared favorably with Gleason score (HR 1.3 for Gleason score 8–10 vs. 6–7; 95% CI 0.8 to 2.0; P=0.31), though neither factor reached statistical significance with the small sample size. The impact of homozygous variant genotype on metastasis (HR 2.8; 95% CI, 1.1 to 6.7; P=0.025) and death (HR 3.5; 95% CI 1.3 to 9.5; P=0.013) was maintained on multivariable analysis. Findings in the external cohorts independently validated the impact of HSD3B1(1245C) on outcomes. Interpretation Inheritance of the HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis is associated with prostate cancer resistance to ADT. Our findings nominate HSD3B1 as a powerful genetic biomarker capable of distinguishing men who are a priori ...