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Purpose: To determine whether β-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Method: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors. Results: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723). Conclusion: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts. [ABSTRACT FROM AUTHOR]

Despite the advent of enormous computing power and the switch to the web as the primary means of reporting empirical research results, papers available online present data on a screen exactly as if it was a printed page. It is now straightforward to program analyses to create interactive figures that allow readers to hover the cursor over a graph and see numerical estimates and tables that allow presentation of data according to user-defined inputs. We recommend that interactive apps for statistical results be routinely included in the HTML versions of medical research papers or as supplementary material. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the safety and efficacy of photoselective vaporization of the prostate in alleviating refractory lower urinary tract symptoms in prostate cancer patients who are managed with active surveillance and to explore the association of this procedure with prostate specific antigen (PSA) levels and cancer progression rates.Methods: Between 2008-2018, active surveillance patients who had refractory symptoms and needed surgery were studied. Perioperative functional variables were collected and analyzed. Disease progression was defined as an upgrade or upstage on surveillance biopsies or multiparametric prostate magnetic resonance imaging. Mean postop scores were estimated using locally-weighted methods. The risk of progression was reported using Kaplan-Meier's method.Results: Seventy-one patients were included in the study. The median age was 68 years and the median surveillance time before surgery was 4 years. At 12 months, there were substantial improvements in the mean International Prostate Symptom Score (18-5.9), maximum flow rate (6.8-14 mL/s), postvoid residual (240-73mL), PSA (8.1-5.2 ng/mL), and prostate volume (85-57mL). At 30-days, only 2 patients with grade-III complications. Late consequences included tissue regrowth in 4 and urethral stricture (requiring a single dilation) in 3 patients. PSA levels decreased by 36% at 12 months postoperatively. With a median follow-up of 3.7 years, 7 men progressed and received radical treatment. At 3 years, the probability of remaining on surveillance was 93% (95% CI 87%- 100%).Conclusion: Photoselective vaporization of the prostate offers substantial relief of symptoms in active surveillance patients with refractory symptoms, without adverse effects on disease progression rates. [ABSTRACT FROM AUTHOR]

The gtsummary package provides an elegant and flexible way to create publication-ready summary tables in R. A critical part of the work of statisticians, data scientists, and analysts is summarizing data sets and regression models in R and publishing or sharing polished summary tables. The gtsummary package was created to streamline these everyday analysis tasks by allowing users to easily create reproducible summaries of data sets, regression models, survey data, and survival data with a simple interface and very little code. The package follows a tidy framework, making it easy to integrate with standard data workflows, and offers many table customization features through function arguments, helper functions, and custom themes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate how surgeon heterogeneity – the variation in outcomes between individual surgeons – influences functional and oncological outcomes after robot‐assisted laparoscopic prostatectomy (RALP) and retropubic radical prostatectomy (RRP), and to assess whether surgeon heterogeneity affects the comparison between RALP and RRP. Patients and Methods: Laparoscopic Prostatectomy Robot Open (LAPPRO) is a prospective, controlled, non‐randomized trial performed at 14 Swedish centres with 68 operating surgeons. A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011. The endpoints were urinary incontinence, erectile dysfunction (ED) and recurrence at 24 months after surgery. Logistic regression models were built to evaluate surgeon heterogeneity and, secondarily, surgeon‐specific factors were added to the models to investigate their influence on heterogeneity and the comparison between RALP and RRP. Results: Among surgeons who performed at least 20 surgeries during the study period (n=25), we observed statistically significant heterogeneity for incontinence (P = 0.001), ED (P < 0.001) and rate of recurrent disease (P < 0.001). The significant heterogeneity remained when analysing only experienced surgeons with a stated experience of at least 250 radical prostatectomies (n=12). Among all participating surgeons (n=68), differences in surgeon volume explained 42% of the observed heterogeneity for incontinence (P = 0.003), 11% for ED (P = 0.03) and 19% for recurrence (P = 0.01). Taking surgeon volume into account when comparing RALP and RRP had a significant impact on the results. The effect was greatest for functional outcomes, and the additional adjustments for the surgeons' previous experience changed whether the difference between techniques was statistically significant or not. The surgeons' annual volume had the greatest effect on the recurrence rate. Conclusions: There was a large degree of heterogeneity among surgeons regarding both functional and oncological outcomes and this had a significant impact on the results when comparing RALP and RRP. Some of the observed heterogeneity was explained by differences in surgeon volume. Efforts to decrease heterogeneity are warranted and variation among surgeons must be accounted for when conducting comparative analyses between surgical techniques. [ABSTRACT FROM AUTHOR]

Background Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45–73 yr during 1991–1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Outcome measurements and statistical analysis Prostate cancer death ( n = 317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Results and limitations Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0 ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr—a similar estimate to that of a man with a PSA of 1.6 ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. Conclusions A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Patient summary Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. [ABSTRACT FROM AUTHOR]

Background Although active surveillance is increasingly used for the management of low-risk prostate cancer, many eligible patients are still nonetheless subject to curative treatment. One argument for considering surgery rather than active surveillance is that the probability of postoperative recovery of erectile function is age dependent, that is, patients who delay surgery may lose the window of opportunity to recover erectile function after surgery. Objective To model erectile function over a 10-yr period for immediate surgery versus active surveillance. Design, setting, and participants Data from 1103 men who underwent radical prostatectomy at a tertiary referral center were used. Outcome measurements and statistical analysis Patients completed the International Index of Erectile Function (IIEF-6) pre- and postoperatively as a routine part of clinical care. Preoperative IIEF-6 scores were plotted against age to assess the natural rate of functional decline due to aging. Reported erectile scores in the 2-yr period following surgery were used to assess post-surgical recovery. Results and limitations Each year increase in patient age resulted in a 0.27 reduction in IIEF scores. In addition to IIEF reducing with increased age, the amount of erectile function that is recovered from presurgery to 12-mo postsurgery also decreases (−0.16 IIF points/yr, 95% confidence interval −0.27, −0.05, p = 0.006). However, delayed radical prostatectomy increased the mean IIEF-6 score over a 10-yr period compared with immediate surgery ( p = 0.001), even under the assumption that all men placed on active surveillance are treated within 5 yr. Conclusions Small differences in erectile function recovery in younger men are offset by a longer period of time living with decreased postoperative function. Better erectile recovery in younger men should not be a factor used to recommend immediate surgery in patients suitable for active surveillance, even if crossover to surgery is predicted within a short period of time. Patient summary Younger men have better recovery of erectile function after surgery for prostate cancer. This has led to the suggestion that delaying surgery for low-risk disease may lead patients to miss a window of opportunity to recover erectile function postoperatively. We conducted a modeling study and found that predicted erectile recovery was far superior on delayed treatment because slightly better recovery in younger men is offset by a longer period of time living with poorer postoperative function in those choosing immediate surgery. [ABSTRACT FROM AUTHOR]

Background A statistical model based on four kallikrein markers (total prostate-specific antigen [tPSA], free PSA [fPSA], intact PSA, and human kallikrein-related peptidase 2) in blood can predict risk of Gleason score ≥7 (high-grade) cancer at prostate biopsy. Objective To determine the value of this model in predicting high-grade cancer at biopsy in a community-based setting in which referral criteria included percentage of fPSA to tPSA (%fPSA). Design, setting, and participants We evaluated the model, with or without adding blood levels of microseminoprotein-β (MSMB) in a cohort of 749 men referred for prostate biopsy due to elevated PSA (≥3 ng/ml), low %fPSA (<20%), or suspicious digital rectal examination at Skåne University Hospital, Malmö, Sweden. Outcome measurements and statistical analysis The kallikrein markers, with or without MSMB levels, measured in cryopreserved anticoagulated blood were combined with age in a published statistical model (Prostate Testing for Cancer and Treatment [ProtecT]) to predict high-grade cancer at biopsy. Predictive accuracy was compared with a base model. Results and limitations The %fPSA was low (median: 17; interquartile range: 13–22) in this cohort because this marker was used as a referral criterion. The ProtecT model improved discrimination over age and PSA for high-grade cancer (0.777 vs 0.720; p = 0.002). At one illustrative cut point, use of the panel would reduce the number of biopsies by 236 per 1000 and detect 195 of 208 (94%) but delay diagnosis of 13 of 208 high-grade cancers. MSMB levels in blood did not improve the accuracy of the panel ( p = 0.2). Conclusions The kallikrein model is predictive of high-grade cancer if criteria for biopsy referral also include %fPSA, and it can reduce unnecessary biopsies without missing an undue number of tumors. Patient summary We evaluated a published model to predict biopsy outcome in men biopsied due to low percentage of free to total prostate-specific antigen. The model helps reduce unnecessary biopsies without missing an undue number of high-grade cancers. [ABSTRACT FROM AUTHOR]

Background Up to 30% of patients with low-risk prostate cancer (PCa) are found to have features of aggressive disease at radical prostatectomy (RP). Several predictive nomograms and novel genomic markers have been developed to estimate the risk of adverse pathology in men eligible for active surveillance (AS). However, oncologic risk associated with these findings remains unknown. Objective To determine if the presence of adverse pathologic features at RP in patients eligible for AS is prognostic of poor oncologic outcome independent of pretreatment risk status. Design, setting, and participants A total of 2660 patients underwent immediate RP at our institution between 1998 and 2008. Patients were stratified as low, intermediate, or high risk according to the D’Amico clinical risk criteria. Outcome measurements and statistical analysis The rates of adverse pathology were reported, and the 5-yr risk of biochemical recurrence (BCR) was calculated in the presence of aggressive disease. Results and limitations The 5-yr risk of BCR in patients with extracapsular extension ( n = 937) was 43% (95% confidence interval [CI], 40–46) overall but only 15% (95% CI, 11–22) for those who met the criteria for low risk ( n = 181). For the 473 patients with pathologic Gleason score 4 + 3, the risk of recurrence at 5 yr was 41% (95% CI, 37–46) overall, 13% (95% CI, 5–27) for low-risk men ( n = 41), 41% (95% CI, 35–47) for intermediate-risk men ( n = 287), and 51% (95% CI, 43–60) for high-risk men ( n = 145). Limitations include use of BCR as the study end point and surrogate for oncologic outcome in men who received curative treatment. Conclusions The presence of pathologically unfavorable disease in patients eligible for AS is not informative as to the safety of this treatment modality. We question the relevance of adverse pathology as the end point for predictive tools designed to guide treatment decisions in low-risk PCa. Patient summary The risk of biochemical recurrence associated with adverse pathologic findings at prostatectomy is reduced by approximately 50% in men with clinically low-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effect of previous prostate surgery performed for lower urinary tract symptoms ( LUTS) on the ability to predict lymph node invasion ( LNI) in patients subsequently diagnosed with prostate cancer, testing two widely used LNI predictive models. Patients and Methods From 1990 to 2012, we collected data on 4734 patients with prostate cancer treated with radical prostatectomy and extended pelvic LN dissection ( ePLND). Of these, 4453 (94%) had no prior prostate surgery ('naïve patients'), while 286 (6%) had previously undergone surgery for LUTS. Two LNI prediction models based on patients treated with ePLND were evaluated using the receiver operating characteristic-derived area under the curve ( AUC), the calibration plot method, and decision-curve analyses. Results The rate of LNI was 12%, while the median number of LNs removed was 15 in both groups ( P = 0.9). The two tested nomograms provided more accurate prediction in naïve patients than for those previously treated with prostate surgery for LUTS ( AUC: 82% and 81% vs 68% and 71%, P = 0.01 and P = 0.04, respectively). In naïve patients the surgeon would have missed one LNI for every 53 and 34 avoided ePLND using the Briganti and Godoy nomograms, respectively; in patients previously treated with surgery for LUTS, a LNI would have been missed in 13 and 21 patients not undergoing ePLND. Conclusion The accuracy and the clinical net-benefit of LNI prediction tools decrease significantly in patients with prior prostate surgery for LUTS. These models should be avoided in such patients, who should undergo routine ePLND. [ABSTRACT FROM AUTHOR]

Background: Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome. Methods: Free, intact and total PSA, and kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men with elevated PSA (=3.0 ng/mL) participating in the prospective, randomized trial Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing anticoagulated plasma were incorporated into statistical models to predict any-grade and high-grade (Gleason score =7) prostate cancer at 10-core biopsy. The models were corrected for optimism by 10-fold cross validation and independently validated using markers measured in serum from 1364 men. All statistical tests were two-sided. Results: The four kallikreins enhanced prostate cancer detection compared with PSA and age alone. Area under the curve (AUC) for the four kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634 (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer, and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for 1000 biopsied men with PSA levels of 3.0 ng/mL or higher, the model would reduce the need for biopsy in 428 men, detect 119 high-grade cancers, and delay diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent discrimination on independent validation among men with only serum samples available for analysis. Conclusions: A statistical model based on kallikrein markers was validated in a large prospective study and reduces unnecessary biopsies while delaying diagnosis of high-grade cancers in few men. [ABSTRACT FROM AUTHOR]

Background: Surgical quality improvement requires accurate tracking and benchmarking of postoperative adverse events. We track surgical site infections (SSIs) with two systems; our in-house surgical secondary events (SSE) database and the National Surgical Quality Improvement Project (NSQIP). The SSE database, a modification of the Clavien-Dindo classification, categorizes SSIs by their anatomic site, whereas NSQIP categorizes by their level. Our aim was to directly compare these different definitions. Materials And Methods: NSQIP and the SSE database entries for all surgeries performed in 2011 and 2012 were compared. To match NSQIP definitions, and while blinded to NSQIP Results, entries in the SSE database were categorized as either incisional (superficial or deep) or organ space infections. These categorizations were compared with NSQIP records; agreement was assessed with Cohen kappa. Results: The 5028 patients in our cohort had a 6.5% SSI in the SSE database and a 4% rate in NSQIP, with an overall agreement of 95% (kappa = 0.48, P < 0.0001). The rates of categorized infections were similarly well matched; incisional rates of 4.1% and 2.7% for the SSE database and NSQIP and organ space rates of 2.6% and 1.5%. Overall agreements were 96% (kappa = 0.36, P < 0.0001) and 98% (kappa = 0.55, P < 0.0001), respectively. Over 80% of cases recorded by the SSE database but not NSQIP did not meet NSQIP criteria. Conclusions: The SSE database is an accurate, real-time record of postoperative SSIs. Institutional databases that capture all surgical cases can be used in conjunction with NSQIP with excellent concordance. [ABSTRACT FROM AUTHOR]

Objective To determine whether the additional benefits of improved prostate cancer detection associated with 5α-reductase inhibitors are sufficient to warrant chemoprevention in the case where the degree of prostate cancer risk reduction is deemed inadequate. Methods We reanalyzed data from REDUCE, a randomized trial of dutasteride for prostate cancer chemoprevention in men with prior negative biopsy. We evaluated whether statistical models using prostate-specific antigen (PSA) and PSA velocity could help predict the result of repeat prostate biopsy separately for dutasteride and placebo groups. Area under the curve was evaluated by 10-fold cross-validation. Results PSA velocity improved discrimination at 4 years in the dutasteride group but not at 2 years nor in the placebo group. At 2 years, dutasteride improved discrimination of PSA slightly (0.616 vs 0.603 for any grade cancer; 0.681 vs 0.676 for high-grade disease). Between-group differences in cancer rates at 4 years were small. Conclusion Clinicians who are willing to treat at least 23 patients with dutasteride for 2 years to avoid 1 prostate cancer diagnosis should offer dutasteride after initial negative biopsy. Clinicians not willing to do so might consider dutasteride for its additional benefit of reducing unnecessary biopsy, although this benefit is apparent only under very restrictive conditions. It is difficult to justify extending treatment with dutasteride for >2 years. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA. Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162). Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality. Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening. [ABSTRACT FROM AUTHOR]

BACKGROUND The Prostate Cancer Prevention Trial (PCPT) Risk Calculator is a widely used prediction tool for aiding decisions about biopsy for prostate cancer. This study hypothesized that recently reported differences between predictions from the model and findings from other cohorts were due to how prostate-specific antigen (PSA) was entered into the statistical model, and to the inclusion of protocol end-of-study biopsies for which there was no clinical indication. METHODS Data was obtained from the 5088 PCPT participants and was used to construct the PCPT Risk Calculator. The relationship between PSA and the risk of a positive biopsy was modeled by using locally-weighted regression (lowess), an empirical estimate of actual risks observed which does not depend on a statistical model. Risks were estimated with and without the 3514 end-of-study biopsies. RESULTS For PSA levels above biopsy thresholds (∼4 ng/mL), the PCPT Risk Calculator greatly overestimated actual empirical risks (eg, 44% versus 26% at 5 ng/mL). The change in risk with increasing PSA was less among for-cause biopsies compared with the end-of-study biopsies ( P = .001). Risk of high-grade disease was overestimated at PSA level of ≥ 6 ng/mL. CONCLUSIONS The PCPT Risk Calculator overestimates risks for PSAs close to and above typical biopsy thresholds. Separating for-cause biopsies from end-of-study biopsies and using empirical rather than model-based risks reduces overall risk estimates and replicates prior findings that, in men who have been screened with PSA, there is no rapid increase in prostate cancer risk with higher PSA. Revision of the PCPT Risk Calculator should be considered. Cancer 2013;119:3007-3011. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether urothelial carcinoma (UC) with sarcomatoid differentiation is associated with a lower pathological response rate to neoadjuvant chemotherapy (NAC) and worse oncological outcomes compared to UC without variant histology among patients undergoing radical cystectomy. Patients and Methods: Patients with UC undergoing cystectomy from 1995 to 2018 at the Memorial Sloan Kettering Cancer Centre were identified. Patients with sarcomatoid differentiation at transurethral resection (TUR) or cystectomy, and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response and pT0N0 defined complete response. Recurrence‐free, cancer‐specific and overall survival were modelled. Results: We identified 131 patients with sarcomatoid differentiation and 1722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received NAC. Those with sarcomatoid differentiation presented with higher consensus tumour stage (94% ≥T2 vs 62%; P < 0.001) and were, therefore, more likely to receive NAC (29% vs 18%; P = 0.003). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and those with pure UC at TUR (P = 0.6). Among patients with sarcomatoid differentiation, 5‐year recurrence‐free survival was 55% (95% confidence interval [CI] 41–74) among patients receiving NAC and 40% (95% CI 31–52) among patients undergoing cystectomy alone (P = 0.1). Adjusting for stage, nodal involvement, margin status and receipt of NAC, sarcomatoid differentiation was associated with worse recurrence‐free (hazard ratio [HR] 1.82, 95% CI 1.39–2.39), disease‐specific (HR 1.66, 95% CI 1.23–2.22), and overall survival (HR 1.37, 95% CI 1.06–1.78). Conclusions: Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathological response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated. [ABSTRACT FROM AUTHOR]

Take Home Message European Urology has established three principles for improving the quality of statistics in papers published in our journal: (1) systematic guidance for authors based on common statistical errors in urology research; (2) all papers with substantive statistics are reviewed by a statistician; and (3) ongoing innovation with respect to statistical reporting. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Radiation therapy for prostate cancer is associated with a 15-20% five-year recurrence rate. Patients with recurrence in the prostate only are candidates for salvage local therapies; however, there is no consensus on modality. This study uses registries at Memorial Sloan Kettering Cancer Center (MSKCC) and University of Western Ontario (UWO) to compare the oncologic outcomes of salvage radical prostatectomy (SRP) and salvage ablation (SA). METHODS: A total of 444 patients were available for analysis. Due to intergroup differences, propensity score methodology was used and identified 378 patients with more comparable pre-salvage prostate-specific antigen (PSA), Gleason score, and primary radiation treatment. Patients underwent SRP at MSKCC and SA at UWO. RESULTS: Of the 378 patients, 48 died of disease, with a 6.0-year median (interquartile range [IQR] 3.0, 9.7) followup among survivors; 88 developed metastases, with a median 4.6-year (IQR 2.3, 7.9) followup among metastasis-free survivors. There was a non-significantly higher rate of cancer-specific (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.51, 2.06, p=0.9) and improved metastasis-free survival (HR 0.71, 95% CI 0.44, 1.13, p=0.15) among patients undergoing SA compared to patients undergoing SRP. There were 143 patients who received hormonal therapy, with higher rates of androgen deprivation therapy (ADT) in SA (HR 1.42, 95% CI 0.97, 2.08, p=0.068), although this did not meet conventional levels of significance. CONCLUSIONS: This propensity score analysis of salvage therapy for radio-recurrent prostate cancer identified no statistically significant differences in oncologic outcome between SRP and SA; however, there was evidence of a lower risk of ADT in the cohort undergoing SRP. Given they are both potentially curative therapies, these treatments are viable options for men with clinically localized, radio-recurrent prostate cancer rather than ADT alone. Future research may further elucidate subpopulations that may be more amenable to either SRP or SA. [ABSTRACT FROM AUTHOR]

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce 6 principles (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. PATIENT SUMMARY: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology. [ABSTRACT FROM AUTHOR]

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce six principles: (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. Patient Summary: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology. [ABSTRACT FROM AUTHOR]

The authors discuss a study comparing robot-assisted laparoscopic radical cystectomy with open surgery. Topics addressed include the performance of open surgery on bladder cancer patients by experienced surgeons and robotic surgery by surgeons experienced in robot-assisted pelvic surgery, rate of complications after surgery, and less intraoperative blood loss in robot-assisted surgery patients. Also mentioned are similar perioperative complications and hospital stay lengths.

• Current smokers reported worse quality of life over a 24-month period. • After radical cystectomy, current smokers also reported higher pain levels. • Smokers should be counseled on the potential for worse convalescence after surgery. Radical cystectomy (RC) has the potential to impact health-related quality of life (HRQOL). Many patients who undergo RC are current or former smokers. To better inform preoperative patient counseling, we examined the association between smoking status and HRQOL after RC. A secondary analysis was performed on a prospective, longitudinal study (2008–2014) examining HRQOL in patients undergoing RC for bladder cancer. We analyzed 12 validated patient-reported outcome measures that focused on functional, symptomatic, psychosocial, and global HRQOL domains. Measures were collected pre-operatively and 3-, 6-, 12-, 18-, and 24-months postoperatively. For each HRQOL domain, we estimated the mean domain scores using a generalized estimation equation linear regression model. Each model included survey time, smoking status, and time-smoking interaction as covariates. Pairwise comparisons of current, former, and never smokers were estimated from the models. Of the 411 patients available for analysis, 29% (n = 119) never smoked, 59% (n = 244) were former smokers, and 12% (n = 48) were current smokers. Over the follow-up period, never smokers compared to current smokers had better global QOL scores (mean difference = +8.9; 95% CI 1.3–16; p = 0.023) and lower pain levels (mean difference = −10; 95% CI −19 to −0.54; p = 0.036). Compared to current smokers, former smokers had marginal improvements in global QOL (+6.9 points) and pain (−7.5 points) during the follow-up period. Current smokers reported worse HRQOL recovery in the 24-months after RC. These findings can be used to counsel patients who smoke on recovery expectations. [ABSTRACT FROM AUTHOR]

Objectives: To determine if the presence of adverse pathological features in patients eligible for active surveillance (AS) are prognostic of poor oncological outcomes, independent of pretreatment risk. Patients and Methods: A retrospective analysis was performed on patients who underwent radical prostatectomy (RP) at two institutions (Cleveland Clinic Foundation and Memorial Sloan Kettering Cancer Center) between 1987 and 2008, and who had subsequent follow‐up. Rates of biochemical recurrence, metastasis and death from prostate cancer were compared amongst patients with adverse pathological features (Gleason score ≥7, ≥pT3, or lymph node invasion) based on D'Amico clinical risk (low vs intermediate/high). We also compared survival outcomes between patients with and without pathological upgrading/upstaging amongst D'Amico low‐risk patients. Univariate and multivariable Cox regression models were used to assess the association between clinical risk, pathological reclassification, and oncological outcomes. Results: We identified 16 341 patients who underwent RP, of whom 6 371 were clinically low‐risk. Adverse outcomes in men with adverse pathological features were significantly lower in those with low clinical risk, with an ~50% and ~70% reduction in the risk of metastasis and death, respectively. Only pathological upgrading/upstaging to Gleason score ≥8, seminal vesicle invasion, and lymph node invasion from clinical low‐risk disease, were associated with adverse outcomes. However, these types of reclassification were rare. Conclusion: Clinical low‐risk patients with pathological upgrading/upstaging have substantially lower rates of important oncological outcomes compared to those with higher pretreatment risk and not substantially different than low‐risk patients without pathological upgrading/upstaging. These results call into question the use of this endpoint to counsel patients about the merits and risks of AS. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact on recovery of bowel function using an 80 mm versus 60 mm gastrointestinal anastomosis (GIA) stapler following radical cystectomy and urinary diversion (RC/UD) for bladder cancer.Methods: We identified 696 patients using a prospectively maintained RC/UD database from January 2006 to November 2010. Two nonrandomized consecutive cohorts were compared. Patients between January 2006- and December 2007 (n = 180) were treated using a 60 mm GIA stapler, and 331 patients between January 2008 and December 2010 were subject to an 80 mm GIA stapler. All patients were treated on the same standardized postoperative recovery pathway. After accounting for baseline patient and perioperative characteristics, using a multivariable logistic regression model, we directly compared rates of postoperative ileus using a standardized definition.Results: Of 511 evaluable patients, ileus was observed in 32% (57/180) for 60 mm GIA versus 33% (110/331) for the 80 mm GIA. Preoperative renal function, age, gender, body mass index, and type of diversion were comparable between cohorts. On multivariate analysis, stapler size was not significantly associated with the development of ileus (GIA-60 vs GIA-80: OR 1.11; 95% CI 0.75, 1.66; P = .6). Positive fluid balance was associated with an increased risk (P = .019) and female sex a decreased risk (P = .008) of developing ileus compared to patients with negative fluid balance.Conclusion: The size of the intestinal bowel anastomosis (GIA 80 mm vs 60 mm) does not independently impact the time to bowel recovery following RC/UD. [ABSTRACT FROM AUTHOR]

The article discusses using four kallikrein markers measured in blood for predicting high-grade cancer at ten-core prostate biopsy in the protecT Study.

Background: Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome.Methods: Free, intact and total PSA, and kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men with elevated PSA (≥3.0ng/mL) participating in the prospective, randomized trial Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing anticoagulated plasma were incorporated into statistical models to predict any-grade and high-grade (Gleason score ≥7) prostate cancer at 10-core biopsy. The models were corrected for optimism by 10-fold cross validation and independently validated using markers measured in serum from 1364 men. All statistical tests were two-sided.Results: The four kallikreins enhanced prostate cancer detection compared with PSA and age alone. Area under the curve (AUC) for the four kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634 (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer, and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for 1000 biopsied men with PSA levels of 3.0ng/mL or higher, the model would reduce the need for biopsy in 428 men, detect 119 high-grade cancers, and delay diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent discrimination on independent validation among men with only serum samples available for analysis.Conclusions: A statistical model based on kallikrein markers was validated in a large prospective study and reduces unnecessary biopsies while delaying diagnosis of high-grade cancers in few men. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening. [ABSTRACT FROM AUTHOR]

In our analysis of men who underwent prostate cancer tumor sequencing, the possibility of a variant being germline in origin varied by gene. Reflex germline testing of DNA damage repair genes should be emphasized given their very high probability of being germline in origin. Tumor-only genomic profiling is an important tool in therapeutic management of men with prostate cancer. Since clinically actionable germline variants may be reflected in tumor profiling, it is critical to identify which variants have a higher risk of being germline in origin to better counsel patients and prioritize genetic testing. To determine when variants found on tumor-only sequencing of prostate cancers should prompt confirmatory germline testing. Men with prostate cancer who underwent both tumor and germline sequencing at Memorial Sloan Kettering Cancer Center from January 1, 2015 to January 31, 2020 were evaluated. Tumor and germline profiles were analyzed for pathogenic and likely pathogenic ("pathogenic") variants in 60 moderate- or high-penetrance genes associated with cancer predisposition. The germline probability (germline/germline + somatic) of a variant was calculated for each gene. Clinical and pathologic factors were analyzed as potential modifiers of germline probability. Of the 1883 patients identified, 1084 (58%) had a somatic or germline pathogenic variant in one of 60 cancer susceptibility genes, and of them, 240 (22%) had at least one germline variant. Overall, the most frequent variants were in TP53 , PTEN , APC , BRCA2 , RB1 , ATM , and CHEK2. Variants in TP53 , PTEN , or RB1 were identified in 746 (40%) patients and were exclusively somatic. Variants with the highest germline probabilities were in PALB2 (69%), MITF (62%), HOXB13 (60%), CHEK2 (55%), BRCA1 (55%), and BRCA2 (47%), and the overall germline probability of a variant in any DNA damage repair gene was 40%. Limitations were that most of the men included in the cohort had metastatic disease, and different thresholds for pathogenicity exist for somatic and germline variants. Of patients with pathogenic variants found on prostate tumor sequencing, 22% had clinically actionable germline variants, for which the germline probabilities varied widely by gene. Our results provide an evidenced-based clinical framework to prioritize referral to genetic counseling following tumor-only sequencing. Patients with advanced prostate cancer are recommended to have germline genetic testing. Genetic sequencing of a patient's prostate tumor may also identify certain gene variants that are inherited. We found that patients who had variants in certain genes, such as ones that function in DNA damage repair, identified in their prostate tumor sequencing, had a high risk for having an inherited cancer syndrome. [ABSTRACT FROM AUTHOR]

Objective To describe fluctuations in prostate-specific antigen ( PSA) levels in men managed with active surveillance ( AS) to determine if a single PSA increase is a consistent measure to use to trigger intervention. Patients and Methods We evaluated data on 541 patients undergoing AS between 1995 and 2011. PSA variation was described by studying the Kaplan-Meier probability of patients' PSA levels reaching 4 or 7 ng/ mL, falling below those thresholds, and then rising to those thresholds again. We also examined PSA variation by calculating the Kaplan-Meier probability of a PSA change followed by an equal or greater change in the opposite direction. Results We analysed data on 541 patients undergoing AS with a median (interquartile range [ IQR]) of 8 (6-12) PSA measurements and undergoing AS for a median ( IQR) of 4 (2-6) years. The 5-year estimate of the probability of reaching a threshold PSA of 7 ng/ mL was 40% (95% confidence interval [ CI] 35-46%) and the 5-year estimate of subsequently falling below this threshold was 90% (95% CI 82-95%). The 5-year estimate of a PSA direction change was 95% (95% CI 93-97%) overall and 56% (95% CI 51-61%) for PSA direction changes of ≥1 ng/ mL. Conclusions We observed a high probability of variability in PSA levels for patients on AS. The probability of changes in PSA, defined by an increase to the specified thresholds or a rise >1 ng/ mL within 6 months and subsequent decrease of equal or greater value on a subsequent measurement, increases over time; therefore, a single change in PSA level is not a reliable endpoint for patients on AS. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the risk of uretero‐enteric anastomotic stricture in patients randomised to open (ORC) or robot‐assisted radical cystectomy (RARC) with extracorporeal urinary diversion. Patients and Methods: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high‐volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non‐malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test. Results: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow‐up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3–5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24‐month estimated glomerular filtration rate between arms (P = 0.15). Conclusions: In this study at a high‐volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed. [ABSTRACT FROM AUTHOR]

Evaluating the postoperative neutrophil-to-lymphocyte (NLR) ratio following nephrectomy for localized renal cell carcinoma and oncological outcomes. A prospectively managed database of 996 patients operated between 2005 and 2020. There was no association between NLR dynamics and disease recurrence. Therefore, there is no clinical role for monitoring the NLR in patients after renal surgery. Introduction & Objectives: In systemic therapy trials, a decreasing neutrophil-to-lymphocyte ratio (NLR) after treatment for metastatic renal cell carcinoma (RCC) has been associated with improved oncologic outcomes. Paradoxically, for patients with localized RCC treated with upfront surgery the opposite effect has been reported. We thus aimed to evaluate NLR dynamics on localized RCC recurrence. Materials and Methods: Treatment naïve patients with localized RCC managed surgically between 2005 and 2020 were included. Preoperative NLR was calculated within 6-weeks prior to surgery and postoperative NLR was calculated bet ween 4 and t welve-weeks after surgery. Patients were followed for disease recurrence, noting metastatic sites and postoperative infections. Cox regression were used to determine whether the relative change in postoperative NLR was associated with metastasis-free survival (MFS) and cancerspecific survival (CSS), adjusted for preoperative NLR. Results: In the cohort of 3310 patients, 996 (30%) had postoperative NLR available. These patients generally had more advanced disease, with 100 developing metastases and 38 dying from kidney cancer. Median MFS follow-up was 4.4 years. Decreasing 2-month postoperative NLR was associated with non-statistically significant worse MFS and CSS (HR 0.79, 95% 0.50, 1.24, P = .3; HR 0.83, 95% C.I. 0.40, 1.73; P = .6). On sensitivity analysis, across all NLR measurements, with NLR as a time-dependent covariate, results were similar, with a declining NLR associated with adverse MFS (HR 0.85, 95% CI 0.69, 1.30, P -value = .10), though not meeting conventional levels of significance. Conclusion: In higher-risk localized RCC patients, postoperative NLR is not suitable as a biomarker for predicting recurrences. [ABSTRACT FROM AUTHOR]

Background: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer.Methods: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting.Findings: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths.Interpretation: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term.Funding: Insightec and the National Cancer Institute. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to report the morbidity profile of salvage radical prostatectomy (SRP) after radiotherapy failure and assess the impact of minimally invasive surgery (MIS) on postoperative complications and functional outcomes. Materials and methods: Between 1985 and 2019, a total of 293 patients underwent SRP; 232 underwent open SRP; and 61 underwent laparoscopic SRP with or without robotic assistance. Complications were recorded and classified into standardized categories per the Clavien-Dindo classification. Results: Twenty-nine patients (10%) experienced grade 3 complications within 30 days, 22 (9.5%) after open and 7 (11%) after MIS (p = 0.6). Between 30 and 90 days after surgery, 7.3% of patients in the open group and 10% in the MIS group had grade 3 complications (p = 0.5). The most common complication was bladder neck contracture (BNC), representing 40% of the 30–90 day complications. Within one year of SRP, 81 patients (31%, 95% CI 25%, 37%) developed BNC; we saw non-significant lower rates in MIS (25 vs 32%; p = 0.4). Functional outcomes were poor after SRP and showed no difference between open and MIS groups for urinary continence (16 vs 18%, p = 0.7) and erectile function (7 vs 13%, p = 0.4). 5 year cancer-specific survival and overall survival was 95% and 88% for the entire cohort, respectively. Conclusions: Our outcomes suggest poor functional recovery after SRP, regardless of the operative approach. Currently there is no evidence favoring the use of open or MIS approach. Further studies are required to ensure comparable outcomes between these approaches. [ABSTRACT FROM AUTHOR]

Objectives To evaluate whether the number of preoperative prostate biopsies affects functional outcomes after radical prostatectomy (RP). Methods We identified patients treated with RP at our institution between 2008 and 2011. At 6 and 12 months postoperatively, the patients completed questionnaires assessing erectile and urinary function. Patients with preoperative incontinence or erectile dysfunction or who did not complete the questionnaire were excluded. Primary outcomes were urinary and erectile function at 12 months postoperatively. We used logistic regression to estimate the impact of number of prostate biopsies on functional outcomes after adjusting for demographic and clinical factors. Results We identified 2 712 patients treated with RP between 2008 and 2011. Most of the patients (80%) had one preoperative prostate biopsy, 16% had two, and 4% had at least three. On adjusted analysis, erectile function at 12 months was not significantly different for patients with two (odds ratio [OR] 1.25; 95% confidence interval [CI] 0.90, 1.75) or three or more (OR 1.52; 95% CI 0.84, 2.78) biopsies, compared with those with one biopsy. Similarly, urinary function at 12 months was not significantly different for patients with two (0.84, 95% CI 0.64, 1.10) or three or more (0.99, 95% CI 0.60, 1.61) biopsies compared with those with one. Conclusions We did not find evidence that a greater number of preoperative prostate biopsies adversely affected erectile or urinary function at 12 months after RP. [ABSTRACT FROM AUTHOR]

Objectives To evaluate whether the number of preoperative prostate biopsies affects functional outcomes after radical prostatectomy ( RP). Methods We identified patients treated with RP at our institution between 2008 and 2011. At 6 and 12 months postoperatively, the patients completed questionnaires assessing erectile and urinary function. Patients with preoperative incontinence or erectile dysfunction or who did not complete the questionnaire were excluded. Primary outcomes were urinary and erectile function at 12 months postoperatively. We used logistic regression to estimate the impact of number of prostate biopsies on functional outcomes after adjusting for demographic and clinical factors. Results We identified 2 712 patients treated with RP between 2008 and 2011. Most of the patients (80%) had one preoperative prostate biopsy, 16% had two, and 4% had at least three. On adjusted analysis, erectile function at 12 months was not significantly different for patients with two (odds ratio [ OR] 1.25; 95% confidence interval [ CI] 0.90, 1.75) or three or more ( OR 1.52; 95% CI 0.84, 2.78) biopsies, compared with those with one biopsy. Similarly, urinary function at 12 months was not significantly different for patients with two (0.84, 95% CI 0.64, 1.10) or three or more (0.99, 95% CI 0.60, 1.61) biopsies compared with those with one. Conclusions We did not find evidence that a greater number of preoperative prostate biopsies adversely affected erectile or urinary function at 12 months after RP. [ABSTRACT FROM AUTHOR]

Background Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8–10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3 + 4 = 7 and 4 + 3 = 7 are often considered the same prognostic group. Objective To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. Design, setting, and participants Between 2005 and 2014, 20 845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. Outcome measurements and statistical analysis Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. Results and limitations In the surgery cohort, we found large differences in recurrence rates between both Gleason 3 + 4 versus 4 + 3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3 + 4, 4 + 3, 8, and 9–10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five–grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. Conclusions The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. Patient summary We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. [ABSTRACT FROM AUTHOR]

Background: We prospectively evaluated the safety and efficacy of adding preoperative chemoprophylaxis to our institution's operative venous thromboembolism (VTE) prophylaxis policy as part of a physician-led quality improvement initiative.Study Design: Patients undergoing major cancer surgery between August 2013 and January 2014 were screened according to service-specific eligibility criteria and targeted to receive preoperative VTE chemoprophylaxis. Bleeding, transfusion, and VTE rates were compared with rates of historical controls who had not received preoperative chemoprophylaxis.Results: The 2,058 eligible patients who underwent operation between August 2013 and January 2014 (post-intervention) were compared with a cohort of 4,960 patients operated on between January 2012 and June 2013, who did not receive preoperative VTE chemoprophylaxis (pre-intervention). In total, 71% of patients in the post-intervention group were screened for eligibility; 82% received preoperative anticoagulation. When compared with the pre-intervention group, the post-intervention group had significantly lower transfusion rates (pre- vs post-intervention, 17% vs 14%; difference 3.5%, 95% CI 1.7% to 5%, p = 0.0003) without significant difference in major bleeding (difference 0.3%, 95% CI -0.1% to 0.7%, p = 0.2). Rates of deep venous thrombosis (1.3% vs 0.2%; difference 1.1%, 95% CI 0.7% to 1.4%, p < 0.0001) and pulmonary embolus (1.0% vs 0.4%; difference 0.6%, 95% CI 0.2% to 1%, p = 0.017) were significantly lower in the post-intervention group.Conclusions: In patients undergoing major cancer surgery, institution of a single dose of preoperative chemoprophylaxis, as part of a physician-led quality improvement initiative, did not increase bleeding or blood transfusions and was associated with a significant decrease in VTE rates. [ABSTRACT FROM AUTHOR]

Background The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. Objective To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. Design, setting, and participants Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. Intervention The 4Kscore. Outcome measurements and statistical analysis The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. Results and limitations Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30–58% in the number biopsies was identified with delayed diagnosis in only 1.3–4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. Conclusion The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. Patient summary The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy. [ABSTRACT FROM AUTHOR]

Background A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. Objective To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants We conducted a case–control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis. Conclusions Screening at ages 50–60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making. [ABSTRACT FROM AUTHOR]

Objective To determine long-term oncological outcomes of radical prostatectomy ( RP) after neoadjuvant chemohormonal therapy ( CHT) for clinically localised, high-risk prostate cancer. Patients and Methods In this phase II multicentre trial of patients with high-risk prostate cancer ( PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥ T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. Results In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence ( BCR-free probability 22%; 95% confidence interval [ CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [ HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival ( HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. Conclusions Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial. [ABSTRACT FROM AUTHOR]

Objective: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer. Patients and Methods: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. Results: In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. Conclusions: Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial. [ABSTRACT FROM AUTHOR]

Differences in outcome after radical prostatectomy for prostate cancer can partly be explained by intersurgeon differences, where degree of experience is one important aspect. This study aims to define the learning curve of robot-assisted laparoscopic prostatectomy (RALP) regarding oncological and functional outcomes. Out of 4003 enrolled patients in the LAPPRO trial, 3583 met the inclusion criteria, of whom 885 were operated on by an open technique. In total, 2672 patients with clinically localized prostate cancer from seven Swedish centres were operated on by RALP and followed for 8 years (LAPPRO trial). Oncological outcomes were pathology-reported surgical margins and biochemical recurrence at 8 years. Functional outcomes included patient-reported urinary incontinence and erectile dysfunction at 3, 12 and 24 months. Experience was surgeon-reported experience before and during the study. The relationship between surgeon experience and functional outcomes and surgical margin status was analysed by mixed-effects logistic regression. Biochemical recurrence was analysed by Cox regression, with robust standard errors. The learning curve for positive surgical margins was relatively flat, with rates of 21% for surgeons who had performed 0–74 cases and 24% for surgeons with > 300 cases. Biochemical recurrence at 4 years was 11% (0–74 cases) and 13% (> 300 cases). Incontinence was stable over the learning curve, but erectile function improved at 2 years, from 38% (0–74 cases) to 53% (> 300 cases). Analysis of the learning curve for surgeons performing RALP showed that erectile function improved with increasing number of procedures, which was not the case for oncological outcomes. [ABSTRACT FROM AUTHOR]

Background Open radical cystectomy (ORC) and urinary diversion in patients with bladder cancer (BCa) are associated with significant perioperative complication risk. Objective To compare perioperative complications between robot-assisted radical cystectomy (RARC) and ORC techniques. Design, setting, and participants A prospective randomized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy (RC), pelvic lymph node dissection (PLND), and urinary diversion. Patients were randomized to ORC/PLND or RARC/PLND, both with open urinary diversion. Patients were followed for 90 d postoperatively. Intervention Standard ORC or RARC with PLND; all urinary diversions were performed via an open approach. Outcome measurements and statistical analysis Primary outcomes were overall 90-d grade 2–5 complications defined by a modified Clavien system. Secondary outcomes included comparison of high-grade complications, estimated blood loss, operative time, pathologic outcomes, 3- and 6-mo patient-reported quality-of-life (QOL) outcomes, and total operative room and inpatient costs. Differences in binary outcomes were assessed with the chi-square test, with differences in continuous outcomes assessed by analysis of covariance with randomization group as covariate and, for QOL end points, baseline score. Results and limitations The trial enrolled 124 patients, of whom 118 were randomized and underwent RC/PLND. Sixty were randomized to RARC and 58 to ORC. At 90 d, grade 2–5 complications were observed in 62% and 66% of RARC and ORC patients, respectively (95% confidence interval for difference, −21% to −13%; p = 0.7). The similar rates of grade 2–5 complications at our mandated interim analysis met futility criteria; thus, early closure of the trial occurred. The RARC group had lower mean intraoperative blood loss ( p = 0.027) but significantly longer operative time than the ORC group ( p < 0.001). Pathologic variables including positive surgical margins and lymph node yields were similar. Mean hospital stay was 8 d in both arms (standard deviation, 3 and 5 d, respectively; p = 0.5). Three- and 6-mo QOL outcomes were similar between arms. Cost analysis demonstrated an advantage to ORC compared with RARC. A limitation is the setting at a single high-volume, referral center; our findings may not be generalizable to all settings. Conclusions This trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing RC/PLND and urinary diversion. Similar 90-d complication rates, hospital stay, pathologic outcomes, and 3- and 6-mo QOL outcomes were observed regardless of surgical technique. Patient summary Of 118 patients with bladder cancer who underwent radical cystectomy, pelvic lymph node dissection, and urinary diversion, half were randomized to open surgery and half to robot-assisted laparoscopic surgery. We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups. Trial Registration ClinicalTrials.gov identifier NCT01076387 , www.clinicaltrials.gov . [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between prostate volume measured from preoperative imaging and adverse pathologic features at the time of radical prostatectomy and evaluate the potential effect of clinical stage on such relationship. Methods: In 1756 men who underwent preoperative magnetic resonance imaging and radical prostatectomy from 2000 to 2010, we examined associations of magnetic resonance imaging-measured prostate volume with pathologic outcomes using univariate logistic regression and with postoperative biochemical recurrence using Cox proportional hazards models. We also analyzed the effects of clinical stage on the relationship between prostate volume and adverse pathologic features via interaction analyses. Results: In univariate analyses, smaller prostate volume was significantly associated with high pathologic Gleason score (P <.0001), extracapsular extension (P <.0001), and positive surgical margins (P = .032). No significant interaction between clinical stage and prostate volume was observed in predicting adverse pathologic features (all P >.05). The association between prostate volume and recurrence was significant in a multivariable analysis adjusting for postoperative variables (P = .031) but missed statistical significance in the preoperative model (P = .053). Addition of prostate volume did not change C-Indices (0.78 and 0.83) of either model. Conclusion: Although prostate size did not enhance the prediction of recurrence, it is associated with aggressiveness of prostate cancer. There is no evidence that this association differs depending on clinical stage. Prospective studies are warranted assessing the effect of initial method of detection on the relationship between volume and outcome. [Copyright &y& Elsevier]

Objective: To determine whether subclassification of positive surgical margins (PSMs) increases predictive ability for biochemical recurrence (BCR) and aids clinical decision‐making in patients undergoing radical prostatectomy. Patients and Methods: We studied 2147 patients with pT2 and pT3a prostate cancer with detailed surgical margin parameters and BCR status. We compared a base model, a linear predictor calculated from the Memorial Sloan Kettering Cancer Center postoperative nomogram (prostate‐specific antigen, pathological tumour grade and stage), with the addition of surgical margin status to five additional models (base model plus surgical margin subclassifications) to evaluate enhancement in predictive accuracy. Decision curve analysis (DCA) was performed to determine the clinical utility of parameters that enhanced predictive accuracy. Results: Among 2147 men, 205 had PSMs, and 231 developed BCR. Discrimination for the base model with addition of surgical margin status was high (c‐index = 0.801) and not meaningfully improved by adding surgical margin subclassification in the full cohort. In analyses considering only men with PSMs (N = 55 with BCR), adding surgical margin subclassification to the base model increased discrimination for total length of all PSMs – alone or with maximum Gleason grade at the margin (c‐index improvement = 0.717 to 0.752 and 0.753, respectively). DCA demonstrated a modest benefit to clinical utility with the addition of these parameters. Conclusions: Specific subclassification parameters add predictive accuracy for BCR and may aid clinical utility in decision‐making for patients with PSMs. These findings may be useful for patient counselling and future adjuvant therapy trial design. [ABSTRACT FROM AUTHOR]

Abstract: Background: The presence of lymph node metastasis (LNM) at radical prostatectomy (RP) is associated with poor outcome, and optimal treatment remains undefined. An understanding of the natural history of node-positive prostate cancer (PCa) and identifying prognostic factors is needed. Objective: To assess outcomes for patients with LNM treated with RP and lymph node dissection (LND) alone. Design, setting, and participants: We analyzed data from a consecutive cohort of 369 men with LNM treated at a single institution from 1988 to 2010. Intervention: RP and extended LND. Outcome measurements and statistical analysis: Our primary aim was to model overall survival, PCa-specific survival, metastasis-free progression, and freedom from biochemical recurrence (BCR). We used univariate Cox proportional hazard regression models for survival outcomes. Multivariable Cox proportional hazard regression models were used for freedom from metastasis and freedom from BCR, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesical invasion, surgical margin status, and number of positive nodes as predictors. Results and limitations: Sixty-four patients with LNM died, 37 from disease. Seventy patients developed metastasis, and 201 experienced BCR. The predicted 10-yr overall survival and cancer-specific survival were 60% (95% confidence interval [CI], 49–69) and 72% (95% CI, 61–80), respectively. The 10-yr probability of freedom from distant metastasis and freedom from BCR were 65% (95% CI, 56–73) and 28% (95% CI, 21–36), respectively. Higher pathologic Gleason score (>7 compared with ≤7; hazard ratio [HR]: 2.23; 95% CI, 1.64–3.04; p < 0.0001) and three or more positive lymph nodes (HR: 2.61; 95% CI, 1.81–3.76; p < 0.0001) were significantly associated with increased risk of BCR on multivariable analysis. The retrospective nature and single-center source of data are study limitations. Conclusions: A considerable subset of men with LNM remained free of disease 10 yr after RP and extended LND alone. Patients with pathologic Gleason score <8 and low nodal metastatic burden represent a favorable group. Our data confirm prior findings and support a plea for risk subclassification for patients with LNM. [Copyright &y& Elsevier]

Objective: To determine the durability of ureteroneocystostomy as well as pre- or post-operative factors that may be associated with failure to provide appropriate renal drainage.Methods: A total of 290 patients who underwent ureteral reimplantation to native bladder between 2003 and 2015 were identified. After excluding pediatric patients and those without any follow-up, 255 patients, 3 of whom had a subsequent contralateral reimplantation were included, for 258 observations. Kaplan-Meier method and univariate Cox models were used to assess whether factors such as radiation, prior abdominal surgery, age at re-implantation, gender and BMI are associated with re-implantation failure.Results: Among 258 observations, there were 27 failures. Median follow-up time was 1.1 years from re-implantation surgery among patients without a failure.1 and 5-year ureteral re-implantation failure is 7% (95% CI 4%, 12%) and 22% (95% CI 15%, 33%), respectively. On univariate analysis, post-operative radiation was found to be strongly associated with poorer ureteral re-implantation survival (HR: 6.62; CI 2.40, 18.29; P = .0003) No significant association between re-implantation failure-free survival and age at reimplantation, gender, BMI, previous abdominal surgery, preoperative radiation and adjuvant radiation was noted (all P > .4).Conclusions: Ureteroneocystotomy in the malignant setting has reasonable success rates through five years. No preoperative factors were associated with re-implantation failure. While all patients need to be followed due to increasing rates of failure with time, patients receiving palliative or salvage radiation therapy appear to be more prone to failure requiring further intervention. [ABSTRACT FROM AUTHOR]