BACKGROUND AND OBJECTIVE:Transperineal (TP) prostate biopsy is increasingly favored over the transrectal (TR) approach because of a lower risk of infection, but comparative data on cancer detection remain limited. We analyzed a large institutional cohort to compare detection rates and disease location between the TP and TR approaches. METHODS:We included all men on active surveillance undergoing prostate biopsy at Memorial Sloan Kettering Cancer Center during the 26-mo transition from TR to TP. Data included demographics, biopsy method, histopathology, and magnetic resonance imaging (MRI) findings. The primary outcome was detection of high-grade cancer (Gleason grade group ≥2). Multivariable logistic regression was adjusted for clinical and imaging variables. Clustered standard errors were used to account for repeat biopsies. KEY FINDINGS AND LIMITATIONS:We identified 1387 biopsies performed in 1304 patients from January 2020 to February 2023. Among all biopsies, 522 (38%) contained high-grade cancer and 602 (43%) contained grade group 1 disease. The empirical rate of high-grade cancer detection was 39% with TP versus 37% with TR biopsy (adjusted odds ratio 0.86, 95% confidence interval 0.66-1.10; p = 0.2). TP biopsy had a higher yield for high-grade anterior disease in comparison to TR biopsy (21% vs 9%; p < 0.001) but a lower yield for high-grade posterior disease (28% vs 34%; p = 0.044). Stratification by Prostate Imaging-Reporting and Data System score on MRI revealed consistent detection patterns across biopsy approaches when assessing disease location. CONCLUSIONS AND CLINICAL IMPLICATIONS:We found no significant difference in the overall detection rate for high-grade cancer between the TR and TP approaches, but there was some evidence of differences by tumor location, with TP biopsy better in sampling anterior tumors, and TR biopsy favoring posterior detection. These findings support the need for further studies, including randomized trials incorporating MRI and detailed location data, to clarify differences between the biopsy approaches in detection rates for different anatomic locations.

BACKGROUND AND OBJECTIVE:Although the effects of 5-α-reductase inhibitors (5-ARIs) on prostate-specific antigen (PSA) have been well-studied, the effects on other kallikrein markers have not been firmly established. Accordingly, a statistical model based on blood measurements of four kallikreins-known commercially as the "4Kscore"-cannot be used for men taking 5-ARIs. We investigated how finasteride affects kallikrein markers and whether suitably adjusted marker levels could be used in the four-kallikrein model to accurately predict the prostate biopsy results. METHODS:We analyzed 500 participants from the Prostate Cancer Prevention Trial (PCPT) with PSA ≤3 ng/ml before finasteride and who had marker measurements after 1 yr on finasteride. Conversion factors were generated from this cohort to estimate prefinasteride marker levels in a separate PCPT cohort of 459 men on finasteride biopsied for cause. Adjusted marker levels were entered into the prespecified 4K model and performance characteristics assessed for predicting high-grade prostate cancer on biopsy. KEY FINDINGS AND LIMITATIONS:Finasteride use halved total PSA (β 0.51, 95% confidence interval 0.49, 0.54). human kallikrein 2 was also halved (β 0.50); free PSA and intact PSA were slightly more than halved (β 0.44 for both). Predictions from the 4K model using adjusted markers improved discrimination over adjusted total PSA alone (AUC 0.734 vs 0.595; p < 0.001). While this cohort underwent only sextant biopsy, the ProtecT model, created on 10-12 core biopsies was still well-calibrated at clinically important thresholds. In decision-curve analysis, the 4K model had the highest net benefit for risk thresholds of ≥7%. CONCLUSIONS AND CLINICAL IMPLICATIONS:The 4K model can be used to inform prostate biopsy decision-making in men taking 5-ARIs for at least 3 mo by incorporating adjusted kallikrein levels into the scoring algorithm.

We undertook a statistical modeling study to determine the effect of implementing population-based prostate-specific antigen (PSA) screening in England on overdiagnosis and PSA testing rates in comparison with the current opportunistic testing policy. Our model merged English data on life expectancy, rates of PSA testing and incidence of prostate cancer by stage with epidemiological data on lead time. In the base scenario, introduction of population-based screening led to an approximate 25% reduction in both PSA testing and overdiagnosis in the population compared with the current policy. This was due to the anticipated decrease in PSA testing and overdiagnosis in men aged 70+ years being larger than the projected increase in PSA testing and overdiagnosis in men 50-69 years. The overall incidence of early-stage prostate cancer was similar. Population-based screening was found to detect more early-stage cancers that were not overdiagnosed, and is therefore likely to have a greater impact on prostate-cancer mortality than current policy. Findings were robust in sensitivity analyses including an entirely independent modeling approach based on the UK Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP). In conclusion, opportunistic screening policies in England have led to high rates of overdiagnosis and PSA testing. A risk-adapted, population-based prostate cancer screening program would likely reduce the number of PSA tests and overdiagnoses, and increase benefits of PSA testing from reduced prostate-cancer mortality. Population health in England would be improved by adopting an organized PSA screening program and policies to reduce opportunistic PSA testing.

Importance:It has been proposed that grade group (GG) 1 prostate cancer should no longer be defined as cancer but as a precancerous condition. One argument raised by critics is this would decrease adherence with essential monitoring (active surveillance) and therefore lead to increased prostate cancer mortality. However, relabeling GG1 prostate cancer also reduces overdiagnosis and overtreatment, and given that these are the major disincentives to prostate-specific antigen (PSA) screening, it should increase use of prostate cancer screening and thereby reduce deaths from prostate cancer. Objective:To model the effects of relabeling of GG1 prostate cancer on prostate cancer mortality in the US. Design, Setting, and Participants:In this decision analytical model created in 2025, the number of men with GG1 cancer and those considering prostate cancer screening with prostate-specific antigen were estimated using US population-based and clinical data published from 2020 to 2025. Exposure:Relabeling GG1 as a precancerous condition. Main Outcomes and Measures:Predicted increase in prostate cancer deaths due to lower adherence with active surveillance vs predicted decrease in prostate cancer deaths due to higher screening rates related to reduced concerns regarding overdiagnosis and overtreatment. Results:In the base case, which was relatively conservative, relabeling would lead to 6-fold more annual prostate deaths avoided than caused (2835 vs 452). Numerous scenarios modifying model inputs failed to change this conclusion. For instance, even if active surveillance progression rate increased by 50%, nonadherence rate doubled, and there was only a 10% absolute increase in screening, annual deaths would be reduced by close to 500. Under the base case, there would be a net decrease in mortality even if the absolute increase in screening rates was only 3%. Conclusions and Relevance:In this study, dropping the cancer label from GG1 prostate disease and redefining GG1 prostate disease as a precancerous lesion led to a net reduction in estimated prostate cancer deaths. Proponents for retaining the cancer label for GG1 prostate disease should argue relabeling would have close to zero effects on screening rates or that other harms outweigh the benefits of reduced prostate cancer mortality.

Background and Objective:Risk stratification in localized prostate cancer relies primarily on Grade group (GG). In GG2-4 disease, risk assignment depends on the proportions of pattern 3 and pattern 4. We hypothesized that total pattern 4 length on biopsy would better predict oncologic outcome than GG, percent pattern 4, and multivariable models ("nomograms") based on clinical variables. Methods:We identified 2499 patients with GG2-4 prostate cancer on biopsy who underwent radical prostatectomy. Discrimination for predictors was calculated for adverse pathologic stage (seminal vesicle invasion or lymph node invasion) and biochemical recurrence (BCR). Key Findings and Limitations:Total pattern 4 length for the case demonstrated the highest discrimination for adverse pathologic stage in comparison with GG (AUC 0.779 vs 0.658; p<0.0001), percent pattern 4 (0.719), and a model including prostate-specific antigen level, clinical stage, GG, PI-RADS score, and number of positive cores (0.762). Results were similar for BCR, with total pattern 4 length outperforming GG (C-index 0.716 vs 0.662), percent pattern 4 (0.695), and the clinical model (0.699). Neither mm of pattern 3 nor the clinical model added discrimination to total mm of pattern 4. Conclusions and Clinical Implications:Total length of Gleason pattern 4 on biopsy best predicts oncologic outcome in GG2-4 prostate cancer. Other common clinicopathologic variables do not further aid discrimination. Further research is warranted to determine the optimal method for quantifying pattern 4 before incorporation into risk stratification algorithms. What does the study add? : Patients with Grade group 2-4 prostate cancer constitute both the largest group and the one in which treatment decision-making is most difficult. For such patients, total length of Gleason pattern 4 on biopsy predicted oncologic outcomes better than Grade group or multivariable models including the standard predictors of stage, grade, PSA, PI-RADS and number of positive cores. Neither mm of pattern 3 nor the standard predictors add discrimination once total length of pattern 4 is known. Patient Summary : Treatment decisions in prostate cancer are often determined by the ratio of pattern 4 to pattern 3 disease. We showed that, in GG2-4 disease, using the total amount of pattern 4 for the case better predicts risk and therefore provides a better basis for treatment decisions. Take Home Message:In Grade group 2-4 prostate cancer, total Gleason pattern 4 length for the case is a stronger predictor of adverse pathologic stage and biochemical recurrence than Grade group and other standard clinical variables. Further research is warranted to determine the optimal method for quantifying pattern 4 before incorporation into risk stratification algorithms.

OBJECTIVE:To measure the sensitivity of prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) for detecting lymph node involvement (LNI) in patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (PLND) and to evaluate whether PSMA nodal status independently predicts oncological outcomes. PATIENTS AND METHODS:We identified patients with localised or locoregional prostate cancer who underwent PSMA-PET/CT followed by RP (2021-2024) at a high-volume centre and had pathologically confirmed LNI (pN1) on PLND. We evaluated the sensitivity of PSMA-PET/CT for detecting pN1 disease. Associations between PSMA-PET/CT and biochemical recurrence (BCR), any radiographic recurrence, and distant recurrence were evaluated using Cox regression models. RESULTS:Overall, PSMA-PET/CT detected LNI in 24 of 79 patients with pN1 disease, a sensitivity of 30% (95% confidence interval [CI] 21-42%). PSMA-positive nodal disease (clinical N1 [cN1]) was significantly associated with BCR (hazard ratio [HR] 2.34, 95% CI 1.26-4.36; P = 0.009), radiographic recurrence (HR 4.23, 95% CI 1.86-9.58; P < 0.001), and distant radiographic recurrence (HR 5.81, 95% CI 1.79-18.8; P = 0.002). The 1-year risk of BCR approached 90% for those with cN1 disease. Median metastatic focus size was larger in cN1 vs cN0 patients (1.1 vs 0.3 cm; P < 0.001). Limitations include relatively short follow-up. CONCLUSIONS:Due to low sensitivity, PSMA-PET/CT without evidence of nodal disease does not obviate the need for PLND. However, PSMA-avid nodal disease portends a nearly inevitable short interval recurrence and radiographic progression, supporting treatment intensification.

BACKGROUND AND OBJECTIVE:Functional recovery after radical prostatectomy happens continually but is only measured at set times when questionnaires are given. This leads to what is known as interval censoring. In the urologic literature, patients are typically considered to have recovered function at the moment they complete a follow-up survey, although recovery may have occurred earlier, leading to systematic overestimation of recovery time. At our institution, patients completing function assessments are additionally asked to estimate when recovery occurred, and this estimate is incorporated into the analysis. We aimed to compare our approach with the standard method, which assigns recovery to the survey completion date. METHODS:We retrospectively identified 11 161 men who underwent radical prostatectomy between 2009 and 2025. Patients completed urinary and erectile function questionnaires at regular intervals after surgery; at the first response meeting recovery criteria (eg, pads no longer used), patients estimated the timing of recovery using predefined intervals. We used Kaplan-Meier analyses to estimate cumulative recovery over time, using both the survey completion date and the patient-reported estimate. KEY FINDINGS AND LIMITATIONS:We identified 7896 patients who recovered continence and 6521 who recovered erectile function. Patient-estimated recovery time was considerably earlier than recovery time based on the survey completion date. Median time to continence recovery was 5 mo using our approach versus 8 mo using the survey completion date approach, whereas median time to erectile function recovery was 18 mo versus 23 mo. At 6 mo, recovery rates were higher when based on patient-estimated dates compared with survey completion dates for both continence (57% vs 40%) and erectile function (35% vs 28%). CONCLUSIONS AND CLINICAL IMPLICATIONS:Functional questionnaires should include an additional item asking patients to report when recovery occurred. The reported time of recovery should be used in the analysis rather than the survey completion date.

INTRODUCTION:Decision aids aim to improve the quality of and satisfaction with decision making. Few scales exist that directly evaluate decision aids from the patient's perspective, particularly with respect to information overload. METHODS:We developed a Decision Aid Evaluation Scale with domains assessing acceptability, satisfaction, cognitive load, and helpfulness for decision making. Cognitive interviews and iterative testing were performed. Convergent and discriminant construct validity were assessed by comparing the novel scale with domains from the validated Decisional Conflict Scale (DCS; values clarity, uncertainty, feeling informed subscales). Internal consistency was measured using Cronbach's alpha. The final scale consisted of Likert-type scale items assessing information amount, values clarity, ease of use, cognitive effort required, nervousness, and overall helpfulness. Participants (any sex or gender, aged 40-60 y) completed the scale after viewing a cancer screening decision aid within a hypothetical screening decision scenario. RESULTS:We surveyed 1,249 participants; 778 completed the Decision Aid Evaluation Scale. As hypothesized, a larger proportion of participants who reported low cognitive load had higher DCS values clarity subscale scores than those with high cognitive load (P = 0.003). Participants who found the decision aid helpful had significantly higher DCS values clarity (P < 0.001), informed (P = 0.004), and certainty subscale scores (P < 0.001). Scores on the acceptability questions were higher among those who found the decision aid helpful (P < 0.001), except for questions related to "length," "relatability of photo," and "photo helped make decision." Participants reporting nervousness had lower DCS certainty subscale scores (P < 0.001). Cronbach's alpha for the acceptability and satisfaction domains were 0.74 and 0.75, respectively, indicating internal consistency. CONCLUSIONS:We developed a patient-centered scale that captures users' perceptions of decision aid usability and information overload. The scale demonstrated acceptable construct validity and internal consistency, supporting its use in evaluating decision aids from the patient perspective.

Effective surgical training requires relatively immediate feedback as to outcomes. This makes surgical learning problematic as some surgical outcomes may take months or years to become apparent. The sequence of surgical gestures, the smallest discrete actions of surgery, during the nerve-sparing step of robot-assisted radical prostatectomy has been used to predict 1-year erectile function (EF) outcomes after surgery. To improve this prediction and extract clinically meaningful insights, we describe the addition of anatomic and functional context to surgical gestures. We analyzed surgical video of 147 patients at 5 surgical centers undergoing robotic-assisted radical prostatectomy. The addition of anatomic and functional characterization to surgical gestures improved model prediction of post-operative EF from 0.78 [95%CI: 0.60, 0.92] to 0.85 [95%CI: 0.66, 0.96]. Aggregated attention weight analysis identified novel gesture, anatomy, and function combinations contributing most to EF outcomes. The identification of these critical gestures provides a starting point for more data-driven training in clinical practice.

Objective:To determine the potential effect of implementing population-based prostate-specific antigen (PSA) screening in England on overdiagnosis and testing rates compared with the current opportunistic testing policy. Design:Statistical modeling study. English data on rates of prostate cancer by stage, symptomatic and asymptomatic PSA testing, and life expectancy were merged with epidemiological assumptions on lead time to evaluate plausible overdiagnosis and PSA testing rates from an organized population-based program, in comparison with the current opportunistic policy. In the base-case scenario, organized screening increased the rate of asymptomatic PSA testing (screening) in men aged 50 - 69 year and decreased PSA testing in older men. An alternative modeling approach estimated change in overdiagnosis using data from the CAP trial, and current asymptomatic cancer detection rates. Setting:England, 2018/19. Participants:Adult men. Main outcome measures:Rates of PSA testing, early-stage prostate cancer incidence, and overdiagnosis (prostate cancer that would not be diagnosed in a man's lifetime but for the PSA test). Results:In the base scenario, introduction of population-based screening led to an approximate 25% reduction in both PSA testing and overdiagnosis rates in the target population compared with the current policy. This was due to the anticipated decrease in PSA testing and overdiagnosis in men aged 70+ years being larger than the projected increase in PSA testing and overdiagnosis in men 50-69 years. The overall incidence of early-stage cancer prostate cancer was similar. Population-based screening was found to detect more early-stage cancers that were not overdiagnosed, and therefore likely to have a greater impact on prostate-cancer morbidity and mortality than current policy. Findings were robust in sensitivity analyses including an entirely separate modeling approach. Conclusion:Opportunistic screening policies in England have led to high rates of overdiagnosis and PSA testing. In comparison with current policy, a risk-adapted, population-based prostate cancer screening program would likely reduce the number of PSA tests and overdiagnoses, and increase benefits of PSA testing from reduced prostate-cancer mortality Population health in England could be improved by either adopting an organized program or by prohibiting PSA testing of asymptomatic men in primary care.

BACKGROUND:Penile Doppler ultrasound (PDUS) is considered the gold standard for diagnosing vascular erectile dysfunction. For optimal results, it is essential to fully relax the cavernosal smooth muscle. AIM:We aimed to profile the end-diastolic velocity (EDV) values and probabilities of delayed erection after PDUS. METHODS:We reported on men who underwent PDUS using a vasoactive agent redosing protocol. The PDUS was performed after the patient achieved full rigidity or the maximum dose of vasoactive agent (up to 100 units) was administered. EDV parameters were assessed. Corporvenocclusive dysfunction (CVOD) was defined as EDV of ≥5 cm/s. Erection rigidity was evaluated 30 minutes after PDUS using the Erection Hardness Scale (EHS). A logistic regression model was created for the outcome of delayed erection (persistent erection or erection achieved after PDUS, EHS ≥ 3) after PDUS with EDV as the predictor. OUTCOMES:EDV values and EHS ≥ 3 after completion of PDUS. RESULTS:722 men were assessed. Median age was 68 (IQR 62, 73) years. 93% had trimix for the PDUS. Most of the patients (72%) received 100 units of the vasoactive agent. The median EHS during PDUS was 2 (2, 3), median EDV 8.3 (IQR 4, 12) cm/s. Five hundred twenty-three (72%) met the criteria for CVOD during the PDUS. However, 25% of the entire cohort and 12% of those with elevated EDV values required erection reversal. When based on EDV values, the probability of delayed erection was 27% of men with an EDV threshold of 5 cm/s and 11% at 10 cm/s. CLINICAL IMPLICATIONS:In a redosing PDUS protocol setting, EDV values are insufficient for CVOD diagnosis. Monitoring delayed erection after PDUS is critical. If the patient remains without delayed erection after PDUS, in men who had PDUS with a redosing protocol and it showed high EDV values, CVOD diagnosis is confirmed. STRENGTHS AND LIMITATIONS:In addition to being an operator-dependent technique, ultrasound can exhibit inter-observer variability. Our rigorous, standardized, and consistent PDUS redosing protocol and the robust statistical analyses are the strengths of this analysis. CONCLUSION:In a redosing PDUS protocol, a higher EDV value indicates a lower probability of delayed erection. A quarter of men with EDV values threshold of 5 cm/s, and one-tenth of men with EDV values at 10 cm/s, thus mandating patient monitoring for delayed erection after completion of the study to confirm CVOD diagnosis.

PURPOSE:We hypothesized that, in patients at high risk for radiation esophagitis (RE), giving sucralfate prophylactically would reduce the need for opioid pain medication. METHODS AND MATERIALS:Patients were enrolled from January 2023 to April 2025 at a single tertiary care center. Patients were randomized to receive 1 g twice a day within the first 5 fractions of radiation therapy (RT), with frequency increased during RT at the clinician's discretion, or standard supportive care. The proportion of patients who took any opioids over the previous 24 hours at the end of the treatment course was compared between groups using logistic regression with the stratification variables and concurrent chemotherapy status as covariates. RESULTS:The trial was closed early due to lack of differences between arms, with 117 patients randomized (n = 56 in the experimental arm). Rates of opioid use were 30% in both groups (absolute adjusted decrease in the prophylactic sucralfate arm -0.4%; 95% CI, -14% to 13%, P > .9). Rates of grade 2 to 3 RE were nonsignificantly lower in the prophylactic sucralfate arm (59% vs 69%, absolute adjusted risk decrease 11%; 95% CI, -7.2% to 28%; P = .2). In patients receiving very high esophageal dose (V60 Gy ≥15%), all controls (n = 4) experienced grade 2 to 3 RE compared with only half of those in the experimental arm (6 of 12) (Fisher's exact test P = .2). CONCLUSIONS:We did not find evidence to support early use of sucralfate in patients at high risk of RE. Limited medical options for the management of RE warrant the continued need to explore further avenues to combat this painful condition.

To determine which treatment parameters optimize focal therapy for intermediate-risk prostate cancer by balancing oncologic control with healthy tissue preservation, in a phase 2b multicenter trial of MRI-guided Focused Ultrasound (MRgFUS). Additionally, to assess the relationship of ablation volume relative to lesion volume with oncologic outcomes, urinary, and erectile function. In this retrospective interpretation of prospectively acquired data, the non-perfused volume (NPV) of prostate tissue encompassing the MRI-visible lesion volume defined the ablation-volume-to-lesion-volume ratio (ALVR). Oncologic efficacy was assessed as the absence of clinically significant (GGG ≥ 2) cancer in the treatment zone at 24-month biopsy. Associations between ALVR and outcomes were assessed using Student’s t-tests. Baseline characteristics were compared using Kruskal–Wallis tests. Eighty-nine men (mean age, 63 years ± 7) had MRI-visible lesions with a volume of 0.47 mL (IQR: 0.20–0.95), with a surrounding NPV of 6.9 mL (IQR: 5.2–10.4). Men achieving oncologic efficacy had twice the ALVR compared to those with recurrence at the treatment site (17 vs 8, mean difference 8.8, 95

24 Background: Anatomic recurrence patterns for surgically resectable high-risk disease with regional node involvement on PSMA-PET are poorly defined. Improved understanding of recurrence patterns can allow for optimization of adjuvant treatment and surveillance strategies. We characterized radiographic recurrence patterns of patients with high-risk prostate cancer who underwent PSMA-PET imaging followed by radical prostatectomy (RP) with pelvic lymph node dissection (PLND) and had pathologic nodal disease (pN1) at surgery. Methods: We identified patients with pN1 disease who underwent RP/PLND for high-risk prostate cancer at our center from 2021 to 2024. Each patient had pre-operative PSMA-PET imaging; those with distant metastases were excluded. Time to radiographic recurrence and location of the most distant radiographic recurrence were recorded. Radiographic recurrence location was categorized as periprostatic, pelvic nodal, or distant (including non-regional lymph nodes, bone or visceral recurrences). We evaluated for association between nodal involvement on pre-operative PSMA-PET (cN1) and presence of 1.) any radiographic recurrence and 2.) distant radiographic recurrence using multivariable and univariable Cox proportional hazards models, respectively. Results: There were 79 patients with surgically resectable disease in the final cohort. Of these, 24 were cN1 on pre-operative PSMA-PET (sensitivity 30%; 95% CI: 21 - 42%). Median follow up was 7 months (IQR 4-13 mo.) among those who remained free of radiographic recurrence. There were 33 patients who developed radiographic recurrence, including 16 with distant recurrence. The Table depicts the anatomic distribution of the most distant radiographic recurrence site. The 1-year adjusted probability of any radiographic recurrence was 28% (95% CI: 9 - 43%) in cN0 disease and 77% (95% CI: 37 - 87%) in cN1 disease. There was a significant association between cN1 status on pre-operative PSMA-PET and any radiographic recurrence (HR 4.23; 95% CI: 1.86 - 9.58; p<0.001) as well as distant radiographic recurrence (HR 5.81; 95% CI: 1.79 - 18.8; p=0.002). Conclusions: Clinical node involvement on pre-operative PSMA-PET is significantly associated with radiographic recurrence for patients with pN1 status following RP/PLND. The high risk of recurrence in these patients supports offering upfront treatment intensification and counseling on the likely need for salvage therapy. Anatomical location of radiographic recurrence on PSMA-PET scan by most distant site of recurrence. Recurrence location by most distant site N = 33 Periprostatic 3 (9%) Pelvic lymph nodes, within ePLND* template 10 (30%) Pelvic lymph nodes, outside of ePLND template 4 (12%) Distant † 16 (48%) *Extended pelvic lymph node dissection. †Includes recurrences in non-regional lymph nodes outside of true pelvis, bones, and visceral organs.