The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Purpose Long-term prostate cancer-specific mortality (PCSM) after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen-detected cancers and the pathological risk factors for PCSM are needed for treatment decision-making. Methods Using Fine and Gray competing risk regression analysis, the clinical and pathological data and follow-up information of 11,521 patients treated by radical prostatectomy at four academic centers from 1987 to 2005 were modeled to predict PCSM. The model was validated on 12,389 patients treated at a separate institution during the same period. Results The overall 15-year PCSM was 7%. Primary and secondary pathological Gleason grade 4–5 (P < 0.001 for both), seminal vesicle invasion (P < 0.001), and year of surgery (P = 0.002) were significant predictors of PCSM. A nomogram predicting 15-year PCSM based on standard pathological parameters was accurate and discriminating with an externally-validated concordance index of 0.92. Stratified by patient age, 15-year PCSM for Gleason score ≤ 6, 3+4, 4+3, and 8–10 ranged from 0.2–1.2%, 4.2–6.5%, 6.6–11%, and 26–37%, respectively. The 15-year PCSM risks ranged from 0.8–1.5%, 2.9–10%, 15–27%, and 22–30% for organ-confined cancer, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis, respectively. Only 3 of 9557 patients with organ-confined, Gleason score ≤ 6 cancers have died from prostate cancer. Conclusions The presence of poorly differentiated cancer and seminal vesicle invasion are the prime determinants of PCSM after radical prostatectomy. The risk of PCSM can be predicted with unprecedented accuracy once the pathological features of prostate cancer are known.

ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.

Purpose: We report results in a series of 3,477 consecutive patients treated with anatomical nerve sparing radical retropubic prostatectomy (RRP) in terms of recovery of erectile function, urinary continence and postoperative complications.Materials and Methods: From May 1983 through February 2003, 1 surgeon (WJC) performed anatomical RRP using a unilateral or bilateral nerve sparing modification when possible. Urinary continence and recovery of erections were evaluated in men with a minimum followup of 18 months. Excluded from potency analysis were men who were not reliably potent before surgery, those who did not undergo a nerve sparing procedure and those who received postoperative adjuvant radiotherapy or hormonal therapy within 18 months of surgery. Other postoperative complications in this patient population were also evaluated.Results: Erections sufficient for intercourse occurred in 76% of preoperatively potent men treated with bilateral (1,770) and 53% of men treated with unilateral or partial nerve sparing (64) surgery. Adequate erectile function was more common following bilateral than unilateral nerve sparing surgery in men younger than 70 years old (78% versus 53%, p ϭ 0.001) compared with those 70 years old or older (52% versus 56%, p ϭ 0.6). Recovery of urinary continence occurred in 93% of all men and was associated with younger age (p ϭ 0.001) but not nerve sparing surgery, tumor stage, prostate specific antigen (PSA), Gleason grade or number of prior prostatectomies performed by the surgeon. Postoperative complications occurred in 320 (9%) of patients and were associated with older age (p Ͻ0.0001), nonnerve sparing surgery (p ϭ 0.001), PSA era (p Ͻ0.0001) and surgeon experience. Complications were not significantly correlated with clinical stage, pathological stage, preoperative PSA or Gleason grade. There was no perioperative mortality.Conclusions: Nerve sparing RRP can be performed with favorable potency and urinary continence. Better results are achieved in younger men. Other complications are reduced with increasing surgeon experience.KEY WORDS: prostatectomy, urinary incontinence, prostatic neoplasms, penile erection Prostate cancer is the most commonly diagnosed noncutaneous malignancy in men older than 60 years. 1 Radical prostatectomy offers the best long-term cancer control for clinically localized disease. However, the possible risk of postoperative complications has deterred some men from choosing this treatment. 2 In 1982 Walsh and Donker introduced the anatomical or nerve sparing radical retropubic prostatectomy (RRP). 3 This operation requires that the prostate be removed with controlled hemostasis, allowing visualization of the urethral sphincter and neurovascular bundles of the corpora cavernosa. Erections and urinary continence can be preserved in the majority of patients and the operative mortality rate is less than 0.5%. 2, 4 -7 Nerve sparing RRP has been performed for 2 decades, yet limited long-term potency and continence data are available in large, prospectively...