Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input wholegenome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts.genomics | prognosis | oncology P rostate cancer is the second leading cause of cancer death and the most common malignancy in men. Given the slow growth rate and low metastatic potential of many primary prostate cancers (1), it is critical to identify those men who can be managed conservatively through active surveillance versus those who need aggressive therapy at time of first diagnosis (2, 3). Today, these treatment decisions are primarily made on the basis of tumor stage, prostate-specific antigen (PSA) level, and the histopathological measure of tumor cell differentiation, the Gleason score. These three factors, together with additional pathological variables assessed in the prostatectomy sample, such as lymph node involvement, are often used to estimate risk of relapse with accuracies in the 70-80% range (3). Postoperative nomograms that incorporate these variables have been developed using large cohorts of typically >1,000 patients and consistently show greater accuracy than preoperative nomograms, where pathological variables are limited to those than can be gleaned from biopsies (4). With increasing interest in active surveillance, however, it is critical to improve risk prediction in the preoperative setting (5, 6).

Objective ● To build a predictive model of urinary continence recovery following radical prostatectomy that incorporates magnetic resonance imaging parameters and clinical data. Patients and Methods ● We conducted a retrospective review of data from 2,849 patients who underwent pelvic staging magnetic resonance imaging prior to radical prostatectomy from November 2001 to June 2010. ● We used logistic regression to evaluate the association between each MRI variable and continence at 6 or 12 months, adjusting for age, body mass index (BMI), and American Society of Anesthesiologists (ASA) score and then used multivariable logistic regression to create our model. ● A nomogram was constructed using the multivariable logistic regression models. Results ● In total, 68% (n=1,742/2,559) and 82% (n=2,205/2,689) regained function at 6 and 12 months, respectively. ● In the base model, age, BMI, and ASA score were significant predictors of continence at 6 or 12 months on univariate analysis (p <0.005). ● Among the preoperative magnetic resonance imaging measurements, membranous urethral length, which showed great significance, was incorporated into the base model to create the full model. ● For continence recovery at 6 months, the addition of membranous urethral length increased the AUC to 0.664 for the validation set, an increase of 0.064 over the base model. For continence recovery at 12 months, the AUC was 0.674, an increase of 0.085 over the base model. Conclusions ● Using our model, the likelihood of continence recovery increases with membranous urethral length and decreases with age, body mass index, and ASA score. ● This model could be used for patient counseling and for the identification of patients at high risk for urinary incontinence in whom to study changes in operative technique that improve urinary function after radical prostatectomy.

Purpose-Recent evidence suggests significantly discordant findings regarding tumor size and the risk of metastases in renal cell carcinoma (RCC). Herein, we present our experience with RCC and evaluate the association between tumor size and risk of metastases in a large cohort of patients.Methods-Using our prospectively maintained nephrectomy database, we identified 2,691 patients treated surgically for a sporadic renal cortical tumor between 1989 and 2008. Associations between tumor size and synchronous metastases at presentation (M1 RCC) were evaluated with logistic regression models while metastases-free survival following surgery was estimated using the KaplanMeier method for 2,367 patients who did not present with M1 RCC and who were followed postoperatively.Results-Among the 2,691 patients, 162 presented with metastatic RCC. Only 1 of 781 patients with a tumor <3cm had M1 RCC at presentation and tumor size was significantly associated with metastases at presentation (odds ratio 1.25 for each 1cm increase, p<0.001). Among the 2,367 patients who did not present with metastases, 171 developed metastatic disease during a median follow-up of 2.8 years. In this group, only 1 of the 720 patients with RCC <3cm developed a de novo metastases during follow-up. Metastases-free survival was significantly associated with tumor size (hazard ratio 1.24 for each 1cm increase, p<0.001).Conclusion-In our experience, tumor size is significantly associated with synchronous metastases and asynchronous metastases following nephrectomy. Our results suggest that risk of metastatic disease for patients with tumors <3cm is negligible.

Purpose Parastomal hernia (PH) is a frequent complication from stoma formation after radical cystectomy (RC). We sought to determine the prevalence and risk factors for developing PH following RC. Material and Methods Retrospective study of 433 consecutive patients who underwent open RC and ileal conduit between 2006-2010. Postoperative cross-sectional imaging studies performed for routine oncologic follow-up (n=1736) were evaluated for PH, defined as radiographic evidence of protrusion of abdominal contents through the abdominal wall defect created by forming the stoma. Univariable and multivariable Cox regression analyses were used to determine clinical and surgical factors associated with PH. Results Complete data were available for 386 patients with radiographic PH occurring in 136. The risk of developing a PH was 27% (95% CI 22-33%) and 48% (95% CI 42-55%) at 1 and 2 years. Clinical diagnosis of PH was documented in 93 patients and 37 were symptomatic. Of 16 patients with clinical PH referred for repair, 8 had surgery. On multivariable analysis, female gender (HR=2.25, 95%CI 1.58-3.21; p<0.0001), higher BMI (HR=1.08 per unit increase 95%CI 1.05-1.12; p<0.0001), and lower preoperative albumin (HR=0.43 per g/dl, 95%CI 0.25-0.75; p=0.003) were significantly associated with PH. Conclusions The overall risk of radiographic evidence of PH approached 50% at 2 years. Female gender, higher BMI, and lower preoperative albumin were most associated with developing PH. Identifying those at greatest risk may allow for prospective surgical maneuvers at the time of initial surgery, such as placement of prophylactic mesh in selected patients, to prevent the occurrence of PH.

Data suggest that patients with cancer recurrence 5 years after nephrectomy are at favorable risk and have long-term median survival. A favorable Memorial Sloan-Kettering Cancer Center risk score and absent symptoms related to metastasis are associated with longer survival in these patients.