James A. Eastham

Background: 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. Objective: To determine when variants found on tumor-only sequencing of prostate cancers should prompt confirmatory germline testing. Design, setting, and participants: 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. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: 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. Patient summary: 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.

Pathology grading of prostate biopsy follows the rule that the highest International Society of Urological Pathology grade group (GG) is the GG assigned. This rule was developed in the systematic biopsy (SBx) era and makes sense when samples are from very different areas of the prostate. This rule has been kept for multiparametric magnetic resonance imaging (mpMRI)-_targeted biopsy (MRI-TBx), for which multiple samples—_targeted and systematic—are taken from small areas. In particular, if the results for SBx and MRI-TBx are discordant, the patient is assigned the higher GG. However, the most appropriate grading when MRI-TBx and SBx grades are discordant has never been investigated empirically. A cohort of patients who have undergone SBx and MRI-TBx with long oncological follow-up does not yet exist. To estimate the risk of recurrence for every combination of biopsy and pathological grades, we used the GG on radical prostatectomy (RP) as a surrogate for GG on MRI-TBx GG surrogate. We analyzed data for 12 468 men who underwent SBx and RP at a tertiary referral center and assessed 5-yr biochemical recurrence-free survival (bRFS) for each pairwise combination of biopsy and surgical GG results. We found that for cases with discordant SBx and RP grades, the risk of recurrence was intermediate, irrespective of whether the highest grade was at RP or SBx. For instance, the 5-yr bRFS rate was 57% for men with GG 3 on RP and 60% for men with GG 3 on SBx, but 63% for men with RP GG 3 and SBx GG 2, and 79% for men with RP GG 2 and SBx GG 3. Translating these findings to MRI-TBx casts doubt on current grading practice: when GGs are discordant between SBx and MRI-TBx, the risk of biochemical recurrence risk is not driven by the highest grade but by an intermediate between the two grades. Our findings should motivate studies assessing long-term outcomes for patients undergoing both MRI-TBx and SBx with a view to empirically evaluating current grading practices. Patient summary: Patients with prostate cancer may undergo two biopsy types: (1) systematic biopsy, for which sampling follows a systematic template; and (2) _targeted biopsy, for which samples are taken from lesions detected on scans. There may be a difference in prostate cancer grade identified by the two approaches. In such cases, the risk of cancer recurrence seems to be predicted by an intermediate grade between the lower and higher grades.

Background: Erectile dysfunction (ED) increases with age. Remarkably, the relationship between age and the risk of ED has only been described in crude categories, such as risk for men aged 50–59 yr, without taking comorbidities into account. Objective: To understand how the risk of patient-reported ED varies according to age and comorbidity status. Design, setting, and participants: This cross-sectional study included a cohort of 17 250 patients with prostate cancer who completed the International Index of Erectile Function erectile function domain (IIEF-EF) questionnaire before any prostate treatment. Outcome measurements and statistical analysis: We created a logistic regression model to predict the probability of ED using age and comorbidities such as cardiovascular disease, diabetes, and hypertension as predictors. We used age as a nonlinear term to allow a curvilinear relationship between age and ED. Results and limitations: The prevalence of patient-reported ED among men without any comorbidities increased from 10% to 79% from the age of 40 and 80 yr. The risk of ED increased sharply with comorbidity: the probability of ED for 50- and 75-yr-old individuals was 20% and 68% for healthy men, but 41% and 85% for those with hypertension, obesity, and diabetes. Men with several comorbidities have the same risk of ED as that of healthy men 15–25 yr older. Limitations include a healthier-than-average patient group and lack of information about some comorbidities and the severity of comorbidities. Conclusions: Our results allow us to better understand how the risk of ED changes with age and comorbidities. Further research should evaluate the impact of other risk factors not considered in the present study and should take risk factor severity into account. Patient summary: Our study shows how the probability of erectile dysfunction (ED) changes with increasing age, analyzed alone and when taking into account the presence of other risk factors for this condition (eg, diabetes, high blood pressure, and cardiovascular disease). Our results help in better understanding the probability of ED for men with and without comorbidities.

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10⁻⁷ and GAB2, p = 2.0 × 10⁻⁶). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC.

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.

Background: Salvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown. Objective: To evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens. Design, setting, and participants: Men who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis. Outcome measurements and statistical analysis: Primary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides. Results and limitations: Of 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%–89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men. Conclusions: In men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer.

Prostate-specific antigen (PSA) density is an established prognostic marker for prostate cancer. We investigated whether the inclusion of PSA density or prostate volume in the Memorial Sloan Kettering Cancer Center nomograms improves the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Among the 11 725 men included, 2140 developed BCR. Neither PSA density nor prostate volume was associated with BCR when added to either the pre-RP or post-RP model (all p values ≥0.10) and changes in the C index were very small (largest change, 0.002). The results were robust to exclusion of outlying prostate volumes and restriction to patients treated after 2005. There is no justification for adding prostate volume or PSA density to BCR nomograms. Patient summary: Addition of prostate volume or prostate-specific antigen density to Memorial Sloan Kettering Cancer Center prediction schemes did not improve the prediction of recurrence of prostate cancer after removal of the prostate.

BACKGROUND: Pelvic lymph node dissection (PLND) is the most reliable procedure for lymph node staging. However, the therapeutic benefit remains unproven; although most radical prostatectomies at academic centers are accompanied by PLND, there is no consensus regarding the optimal anatomical extent of PLND. OBJECTIVE: To evaluate whether extended PLND results in a lower biochemical recurrence rate. DESIGN, SETTING, AND PARTICIPANTS: We conducted a single-center randomized trial. Patients, enrolled between October 2011 and March 2017, were scheduled to undergo radical prostatectomy and PLND. Patients were assigned to limited or extended PLND by cluster randomization. Specifically, surgeons were randomized to perform limited or extended PLND for 3-mo periods. INTERVENTION: Randomization to limited (external iliac nodes) or extended (external iliac, obturator fossa and hypogastric nodes) PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate of biochemical recurrence. RESULTS AND LIMITATIONS: Of 1440 patients included in the final analysis, 700 were randomized to limited PLND and 740 to extended PLND. The median number of nodes retrieved was 12 (interquartile range [IQR] 8-17) for limited PLND and 14 (IQR 10-20) extended PLND; the corresponding rate of positive nodes was 12% and 14% (difference -1.9%, 95% confidence interval [CI] -5.4% to 1.5%; p = 0.3). With median follow-up of 3.1 yr, there was no significant difference in the rate of biochemical recurrence between the groups (hazard ratio 1.04, 95% CI 0.93-1.15; p = 0.5). Rates for grade 2 and 3 complications were similar at 7.3% for limited versus 6.4% for extended PLND; there were no grade 4 or 5 complications. CONCLUSIONS: Extended PLND did not improve freedom from biochemical recurrence over limited PLND for men with clinically localized prostate cancer. However, there were smaller than expected differences in nodal count and the rate of positive nodes between the two templates. A randomized trial comparing PLND to no node dissection is warranted. PATIENT SUMMARY: In this clinical trial we did not find a difference in the rate of biochemical recurrence of prostate cancer between limited and extended dissection of lymph nodes in the pelvis. This study is registered on ClinicalTrials.gov as NCT01407263.

CONTEXT: Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial. OBJECTIVE: To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging). EVIDENCE ACQUISITION: We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. EVIDENCE SYNTHESIS: A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging. CONCLUSIONS: A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT. PATIENT SUMMARY: We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases.

Patient-reported outcome instruments for erectile function often ask respondents about their experience over the previous 4wk. This is problematic for baseline assessment of patients with prostate cancer (PC) before treatment, as the previous 4wk would probably have involved procedures such as biopsy and considerable anxiety related to their diagnosis. At San Raffaele Hospital, the International Index of Erectile Function (IIEF-6) was used to ask new PC patients about function in both the previous 4wk and 6mo. We compared responses to these two timeframes. IIEF-6 scores were lower for the 4-wk period (median 24 vs 26; p<0.0001) predominately because approximately one in six of patients with good function in the 6-mo time frame had very poor function in the 4wk before completing the questionnaire (adequate erectile function 60% and 51%; absolute difference 9%, 95% confidence interval 8-10%). Results were further confirmed using a comparison group of 5395 patients with PC newly diagnosed at Memorial Sloan Kettering Cancer Center who had similar function in the previous 6mo. Erectile function evaluation for men presenting with PC should involve asking about typical function over a 6-mo period rather than focusing on the previous 4wk. PATIENT SUMMARY: Questionnaires to assess erectile function often ask men about function in the previous 4wk. We found that this underestimates function in new prostate cancer patients and that such men should be asked about typical function over a 6-mo period.

CONTEXT: Pelvic lymph node dissection (PLND) yields the most accurate staging in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), although it can be associated with morbidity. OBJECTIVE: To systematically evaluate the impact of PLND extent on perioperative morbidity in patients undergoing RP. A new PLND-related complication assessment tool is proposed. EVIDENCE ACQUISITION: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was conducted. MEDLINE/PubMed, Scopus, Embase and Web of Science databases were searched to yield studies discussing perioperative complications following RP and PLND. The extent of PLND was classified according to the European Association of Urology PCa guidelines. Studies were categorized according to the extent of PLND. Intra- and postoperative complications were classified as "strongly," "likely," or "unlikely" related to PLND. Anatomical site of perioperative complications was recorded. A cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS: Our search generated 3645 papers, with 176 studies meeting the inclusion criteria. Details of 77 303 patients were analyzed. Of these studies, 84 (47.7%), combining data on 28 428 patients, described intraoperative complications as an outcome of interest. Overall, 534 (1.8%) patients reported one or more intraoperative complications. Postoperative complications were reported in 151 (85.7%) studies, combining data on 73 629 patients. Overall, 10 401 (14.1%) patients reported one or more postoperative complication. The most reported postoperative complication strongly related to PLND was lymphocele (90.6%). The pooled meta-analysis revealed that RP + limited PLND/standard PLND had a significantly decreased risk of experiencing any intraoperative complication (risk ratio [RR]: 0.55; p =  0.01) and postoperative complication strongly related to PLND (RR: 0.46; p =  <0.00001), particularly for lymphocele formation (RR: 0.52; p =  0.0003) and thromboembolic events (RR: 0.59; p =  0.008), when compared with extended/superextended PLND. The extent of PLND was confirmed to be an independent predictor of lymphocele formation (RR: 1.77; p <  0.00001). CONCLUSIONS: The perioperative morbidity of PLND in patients undergoing RP and PLND for PCa significantly correlates with the extent of PLND. More standardized reporting of intra- and postoperative complications is needed to better estimate the direct impact of PLND extent on perioperative morbidity. PATIENT SUMMARY: Pelvic lymph node dissection (PLND) is the most accurate method for staging in patients undergoing radical prostatectomy for prostate cancer, although it can be associated with complications. This study aims to systematically evaluate the impact of PLND extent on perioperative complications in these patients. We found that intra- and postoperative complications correlate significantly with the extent of PLND. A more rigorous assessment and thorough reporting of perioperative complications are recommended.

We propose a new terminology for assessing the risk of prostate cancer among men aged >70 yr: “PSA surveillance in the septuagenarian.”

Background: In men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy. Objective: To determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy. Methods: We analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years. Results: Patients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely. Conclusions: We can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.

Background: Active surveillance (AS) protocols rely on rectal examination, prostate-specific antigen, imaging, and biopsy to identify disease progression. Objective: To evaluate whether an AS regimen based on magnetic resonance imaging (MRI) or clinical stage changes can detect reclassification to grade group (GG) ≥2 disease compared with scheduled systematic biopsies. Design, setting, and participants: We identified a cohort of men initiated on AS between January 2013 and April 2016 at a single tertiary-care center. Patients completed confirmatory testing and prostate MRI prior to enrollment, then underwent laboratory and physical evaluation every 6 mo, MRI every 18 mo, and biopsy every 3 yr. Outcome measurements and statistical analysis: MRI results were evaluated using composite Likert/Prostate Imaging Reporting and Data System v2 scoring. MRI and clinical changes were assessed for association with disease progression. Univariable and multivariable regression models were used to predict upgrading on 3-yr biopsy. Results and limitations: At 3 yr, of 207 men, 66 (32%) had ≥ GG2 at biopsy: 55 (83%) with GG2, 10 (15%) with GG3, and one (1.5%) with GG4. Among patients with a 3-yr MRI score of ≥3, 41% had ≥ GG2 disease, compared with 15% with an MRI score of <3 (p = 0.0002). The MRI score increased in 48 men (23%), decreased in 27 (13%), and was unchanged in 132 (64%) men. Increases in MRI score were not associated with reclassification after adjusting for the 3-yr MRI score (p = 0.9). Biopsying only for an increased MRI score or clinical stage would avoid 681 biopsies per 1000 men, at the cost of missing ≥GG2 disease in 169 patients. Conclusions: An AS strategy that uses MRI or clinical changes to trigger prostate biopsy avoids many biopsies but misses an unacceptable amount of clinically significant disease. Prostate biopsy for men on AS should be performed at scheduled intervals, regardless of stable imaging or examination findings. Patient summary: An active surveillance strategy for biopsy based only on increases in magnetic resonance imaging score or clinical stage will avoid many biopsies; however, it will miss many patients with clinically significant prostate cancer. Negative magnetic resonance imaging (MRI) on active surveillance (AS) cannot justify avoiding scheduled biopsy as the risk of clinically significant disease is too great. AS protocols should involve prostate-specific antigen, MRI, and physical examination combined with scheduled repeat biopsy.

Introduction: Erectile function, libido, and sexual bother are incompletely correlated: a man may or may not be satisfied for a given level of erectile function; similarly, 2 men may have the same erectile function and different levels of sexual desire. Aim: To explore the relationship between erectile function, sexual satisfaction and sexual desire. Methods: We examined the Spearman correlation among erectile function (International Index of Erectile Function [IIEF-6]), sexual desire, and sexual bother in 3,944 questionnaires completed by patients after radical prostatectomy as part of routine care. IIEF-6 scores were adjusted if a patient indicated that the reason for not having intercourse was other than lack of ability of confidence (eg, lack of partner). Main Outcome Measure: Patient-reported outcome instruments. Results: Median age at surgery and preoperative IIEF-6 were 63 years and 26, respectively. Among questionnaires completed after surgery, there was moderate correlation among the IIEF-6 score and both sexual desire (Spearman rho: 0.41) and sexual bother (Spearman rho: 0.30). In men who reported high or moderate bother relating to sexual function, there was a narrow distribution of erectile function scores, with most men reporting poor function (median IIEF-6: 6, interquartile range 3, 11). For men who reported small or no problem with sexual function, the distribution of erectile function scores was wide, and particularly bimodal as a function of sexual desire. Among patients with high desire, the correlation between sexual bother and erectile function was 0.61 (ie, the poorer is your function, the greater you are bothered), whereas it was -0.081 among patients with low desire, meaning that some men are not bothered by poor erections. Clinical Implications: We provided useful insights to help physicians during sexual counselling after surgery for prostate cancer. Strength & Limitations: The study included a large number of patients and provides evidence for implementation of patient-reported outcome insturments. Limitations include the retrospective nature of our data. Conclusion: Sexual desire helps explain the moderate correlation between erectile function and sexual bother. Sexual desire and bother questions should be incorporated in patient-reported outcome instruments for male sexual function. Bravi CA, Tin A, Montorsi F, et al. Erectile Function and Sexual Satisfaction: The Importance of Asking About Sexual Desire. J Sex Med 2020;17:349–352.

Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. _targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI. Non-invasive tools are needed to reveal metabolic phenomena in humans. In this translational study, Granlund et al. utilize metabolic imaging to interrogate prostate cancer, finding a mechanistic link between increased metabolism and tumor grade. Thus, real-time metabolic imaging in humans can not only provide clinically relevant tools but also uncover new biology.

CONTEXT: Recent studies suggested that magnetic resonance imaging (MRI) followed by _targeted biopsy ("MRI-stratified pathway") detects more clinically significant prostate cancers (csPCa) than the systematic transrectal ultrasound-guided prostate biopsy (TRUS-Bx) pathway, but controversy persists. Several randomized clinical trials (RCTs) were recently published, enabling generation of higher-level evidence to evaluate this hypothesis. OBJECTIVE: To perform a systematic review and meta-analysis of RCTs comparing the detection rates of csPCa in the MRI-stratified pathway and the systematic TRUS-Bx pathway in patients with a suspicion of prostate cancer (PCa). EVIDENCE ACQUISITION: PubMed, EMBASE, and Cochrane databases were searched up to March 18, 2019. RCTs reporting csPCa detection rates of both pathways in patients with a clinical suspicion of prostate cancer were included. Relative csPCa detection rates of the MRI-stratified pathway were pooled using random-effect model. Study quality was assessed using the Cochrane risk of bias tool for randomized trials. A comparison of detection rates of clinically insignificant PCa (cisPCa) and any PCa was also performed. EVIDENCE SYNTHESIS: Nine RCTs (2908 patients) were included. The MRI-stratified pathway detected more csPCa than the TRUS-Bx pathway (relative detection rate 1.45 [95% confidence interval {CI} 1.09-1.92] for all patients, and 1.42 [95% CI 1.02-1.97] and 1.60 [95% CI 1.01-2.54] for biopsy-naïve and prior negative biopsy patients, respectively). Detection rates were not significantly different between pathways for cisPCa (0.89 [95% CI 0.49-1.62]), but higher in the MRI-stratified pathway for the detection of any PCa (1.39 [95% CI 1.05-1.84]). CONCLUSIONS: The MRI-stratified pathway detected more csPCa than the systematic TRUS-guided biopsy pathway in men with a clinical suspicion of PCa, for both biopsy-naïve patients and those with prior negative biopsy. The detection rate of any PCa was higher in the MRI-stratified pathway, but not significantly different from that of cisPCa. PATIENT SUMMARY: Our meta-analysis of clinical trials shows that the magnetic resonance imaging-stratified pathway detects more clinically significant prostate cancers than the transrectal ultrasound-guided prostate biopsy pathway in men with a suspicion of prostate cancer.

Introduction: Given the number of confounders in predicting erectile function recovery after radical prostatectomy (RP), a nomogram predicting the chance to be functional after RP would be useful to patients’ and clinicians’ discussions. Aim: To develop preoperative and postoperative nomograms to aid in the prediction of erectile function recovery after RP. Main Outcome Measures: International Index of Erectile Function (IIEF) erectile function domain score-based erectile function. Methods: A prospective quality-of-life database was used to develop a series of nomograms using multivariable ordinal logistic regression models. Standard preoperative and postoperative factors were included. Main Outcome Measures: The nomograms predicted the probability of recovering functional erections (erectile function domain scores ≥24) and severe erectile dysfunction (≤10) 2 years after RP. Results: 3 nomograms have been developed, including a preoperative, an early postoperative, and a 12-month postoperative version. The concordance indexes for all 3 exceeded 0.78, and the calibration was good. Clinical Implications: These nomograms may aid clinicians in discussing erectile function recovery with patients undergoing RP. Strengths & Limitations: Strengths of this study included a large population, validated instrument, nerve-sparing grading, and nomograms that are well calibrated with excellent discrimination ability. Limitations include current absence of external validation and an overall low comorbidity index. Conclusions: It is hoped that these nomograms will allow for a more accurate discussion between patients and clinicians regarding erectile function recovery after RP. Mulhall JP, Kattan MW, Bennett NE, et al. Development of Nomograms to Predict the Recovery of Erectile Function Following Radical Prostatectomy J Sex Med 2019;16:1796–1802.

Acute kidney injury (AKI) negatively affects long-term functional recovery after partial nephrectomy and thus should be prevented. The duration of injury is informative, and should be included in the assessment of AKI and in future studies addressing this topic.

Introduction: The use of multiparametric magnetic resonance imaging (mpMRI) to assess prostate cancer (PCa) has increased over the past decade. We aimed to assess if preoperative mpMRI lesion score, a variable routinely available for men undergoing pre-biopsy MRI, improves the performance of commonly used preoperative predictive models for PCa recurrence. Patients and Methods: We analyzed data from 372 patients with PCa treated with radical prostatectomy in 2012 to 2017 and assessed with pre-biopsy mpMRI within 6 months prior to surgery. Suspicious areas for cancer were scored on a standardized 5-point scale. Cox regression was used to assess the association between mpMRI score and the risk of postoperative biochemical recurrence. Two different models were tested accounting for factors included in the Kattan nomogram and in the D'Amico risk-classification. Results: Overall, 53% and 30% of patients were found with a lesion scored 4 or 5 at pre-biopsy mpMRI, respectively. Risk varied widely by mpMRI (29% 2-year risk of biochemical recurrence for a score of 5 vs. 5% for a score of 1-2), and mpMRI score was associated with large hazard ratios after adjusting for stage, grade, and prostate-specific antigen: 1.66, 1.96, and 2.71 for scores 3, 4, and 5, respectively. However, 95% confidence intervals were very wide (0.19-14.20, 0.26-14.65, and 0.36-20.55, respectively) and included 1. Conclusions: Our data did not show that preoperative models, commonly used to assess PCa risk, were improved after including the pre-biopsy mpMRI score. However, the value of pre-biopsy mpMRI to improve preoperative risk models should be investigated in larger data sets.

Objective: To describe contemporary management and outcomes of patients experiencing postoperative hemorrhage after minimally invasive radical prostatectomy. Materials and Methods: We retrospectively analyzed data from patients who underwent minimally invasive radical prostatectomy at our institution between January 2010 and January 2017. Clinically significant hemorrhage was defined as a decrease in hemoglobin of ≥30% or 4 g/dL from preoperative to 4 or 14 hours postoperative measurement, receiving a blood transfusion within 30 days, or undergoing a secondary procedure to control bleeding. Patients were analyzed in 3 groups: (1) serially monitored only, (2) received a blood transfusion, and (3) underwent a secondary procedure. Outcomes included imaging studies performed, length of stay, emergency room visits, hospital readmissions, complication rates, and functional outcomes. Results: Of 3749 men, 4% (151/3749) had clinically significant hemorrhage, 1.6% (60/3749) received a transfusion; 0.32% (12/3749) underwent a secondary procedure to control bleeding. In a 30-day composite outcome, increased healthcare utilization (emergency room visit, readmission, or Grade ≥3 complications), was seen in 25% of the serial monitoring group, 65% of the transfusion group, and 100% in the secondary procedure group. This rate in 3598 men without hemorrhage was 12.5%. One-year erectile function was poorest in men who underwent a secondary procedure. Urinary functional outcomes were similar in the 3 groups. Conclusion: Most patients experiencing clinically significant hemorrhage will stabilize without transfusion, and a very small fraction require secondary intervention. Patients experiencing milder bleeding events utilized additional healthcare resources at approximately twice the rate of those who did not, warranting appropriate counseling and postoperative monitoring.