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Background: Evidence suggests that minimally invasive radical prostatectomy (MRP) and open radical prostatectomy (ORP) have similar short-term clinical and functional outcomes. MRP with robotic assistance is generally more expensive than ORP, but it is not clear whether subsequent costs of care vary by approach.Methods: In the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked with Medicare claims, men aged 66 years or older who received MRP or ORP in 2003 through 2006 for prostate cancer were identified. Total cost of care was estimated as the sum of Medicare payments from all claims for hospital care, outpatient care, physician services, home health and hospice care, and durable medical equipment in the first year from the date of surgical admission. The impact of surgical approach on costs was estimated, controlling for patient and disease characteristics.Results: Of 5445 surgically treated prostate cancer patients, 4454 (82%) had ORP and 991 (18%) had MRP. Mean total first-year costs were more than $1200 greater for MRP compared with ORP ($16,919 vs $15,692; P = .08). Controlling for patient and disease characteristics, MRP was associated with 2% greater mean total payments, but this difference was not statistically significant. First-year costs were greater for men who were older, black, lived in the Northeast, had lymph node involvement, more advanced tumor stage, or greater comorbidity.Conclusions: In this population-based cohort of older men, MRP and ORP had similar economic outcomes. From a payer's perspective, any benefits associated with MRP may not translate to net savings compared with ORP in the first year after surgery. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate changes in clinical and pathologic characteristics of prostate cancer in patients who underwent surgery at a large tertiary care center in the context of increased use of active surveillance (AS) and minimally invasive surgery (MIS).Methods: The authors retrospectively reviewed 6624 patients with localized prostate cancer who underwent radical prostatectomy from 2000 to 2010 at Memorial Sloan-Kettering Cancer Center. Patients were stratified by surgical approach (open, laparoscopic, or robotic) and by risk category (low, intermediate, or high). Patients with low-risk disease, without intervention, and with a minimum follow-up of 6 months were considered to have elected AS.Results: The number of patients who had AS increased from <20 per year between 2000 and 2004 to ≥ 100 per year between 2007 and 2009. Over the same decade, the number of patients who underwent MIS (laparoscopic or robotic) increased from zero to 63% of all surgical cases. The percentage of patients in the intermediate-risk and high-risk categories increased over time, whereas the percentage of patients in the low-risk category decreased (odds ratio [OR] per year, 0.91; 95% confidence interval [CI], 0.89-0.92; P < .0005). The proportion of patients who underwent surgery with Gleason 6 tumors decreased over time (OR per year, 0.87; 95% CI, 0.85-0.88; P < .0005), whereas pathologic stage and Gleason score increased (P < .0005). The proportion of low-risk patients decreased across all types of surgery, and the largest decrease was observed for robotic surgery (P < .0005).Conclusions: A reverse stage shift was observed in patients who underwent radical prostatectomy after 2000 despite the introduction and rapid proliferation of MIS. This shift may have been caused in part by the increased use of AS and an institutional focus on the treatment of higher risk disease. [ABSTRACT FROM AUTHOR]

While technically challenging, salvage prostatectomy provides excellent local control of radiorecurrent cancer and can eradicate the disease in a high proportion of patients whose cancer is confined to the prostate or immediate periprostatic tissue. An even greater challenge, perhaps, is to detect local recurrence while the cancer is still amenable to salvage therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Numerous technical modifications to radical prostatectomy have been proposed. Such modifications are likely to lead to only slight improvements in outcomes. Although small differences would be worthwhile, an appropriately powered randomized trial would need to be very large, and thus of doubtful feasibility given the expense, complexity and regulatory burden of contemporary clinical trials. We have proposed a novel methodology, the clinically-integrated randomized trial, which dramatically streamlines trial procedures in order to reduce the marginal cost of an additional patient towards zero. We aimed to determine the feasibility of implementing such a trial for radical prostatectomy. Methods Patients undergoing radical prostatectomy as initial treatment for prostate cancer were randomized in a factorial design to involvement of the fascia during placement of the anastomotic sutures, urethral irrigation, both or neither. Endpoint data were obtained from routine clinical documentation. Accrual and compliance rates were monitored to determine the feasibility of the trial. Results From a total of 260 eligible patients, 154 (59%) consented; 56 patients declined to participate, 20 were not approached on recommendation of the treating surgeon, and 30 were not approached for logistical reasons. Although recording by surgeons of the procedure used was incomplete (~80%), compliance with randomization was excellent when it was recorded, with only 6% of procedures inconsistent with allocation. Outcomes data was received from 71% of patients at one year. This improved to 83% as the trial progressed. Conclusions A clinically-integrated randomized trial was conducted at low cost, with excellent accrual, and acceptable compliance with treatment allocation and outcomes reporting. This demonstrates the feasibility of the methodology. Improved methods to ensure documentation of surgical procedures would be required before wider implementation. Trial registration ClinicalTrials.gov NCT00928850

Abstract Background Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. Methods We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Results Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. Conclusions We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice.

Abstract Background We propose a novel framework for management of cancer survivorship: electronic patient Self-Assessment and Management (SAM). SAM is a framework for transfer of information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice. Methods Patients who participate in the SAM system are contacted by email at regular intervals and asked to complete validated questionnaires online. Patient responses on these questionnaires are then analyzed in order to provide patients with real-time, online information about their progress and to provide them with tailored and standardized medical advice. Patient-level data from the questionnaires are ported in real time to the patient's health care provider to be uploaded to clinic notes. An initial version of SAM has been developed at Memorial Sloan-Kettering Cancer Center (MSKCC) and the University of California, San Francisco (UCSF) for aiding the clinical management of patients after surgery for prostate cancer. Results Pilot testing at MSKCC and UCSF suggests that implementation of SAM systems are feasible, with no major problems with compliance (> 70% response rate) or security. Conclusion SAM is a conceptually simple framework for passing information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice.

Abstract Background Based on a large, representative unscreened cohort from Malmö, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis. Methods In 1974–1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer. Results Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer (area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher). Conclusion A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.

Importance: Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known., Objective: To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer., Design, Setting, and Participants: This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024., Intervention: Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring., Main Outcomes and Measures: Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed., Results: A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (-4.3% to 14.0%) for 90 minutes per week, 2.4% (-1.3% to 6.2%) for 150 minutes per week, -1.3% (-5.8% to 3.3%) for 225 minutes per week, -0.2% (-4.0% to 3.7%) for 300 minutes per week, -2.6% (-9.2% to 4.1%) for 375 minutes per week, and 2.2% (-0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (-1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (-1.1 to 1.5) for 150 minutes per week, -0.5 ng/mL (-1.2 to 0.3) for 225 minutes per week, -0.2 (-1.7 to 1.3) for 300 minutes per week, -0.7 ng/mL (-1.7 to 0.4) for 375 minutes per week, and -0.9 ng/mL (-2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 45 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose., Conclusions and Relevance: The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT03813615.

Background: During active surveillance (AS) for Grade Group (GG) 2 prostate cancer, pathologic progression to GG3 on surveillance biopsy is a trigger for intervention. However, this ratio of GP3:GP4, may be obscured by increases of relatively indolent disease. We aimed to explore changes in GP4 quantity during AS and propose alternative definitions for progression based on GP4 changes., Design, Setting, and Participants: We assessed patients enrolled on AS between November 2014 and March 2020 with GG2 disease on diagnostic biopsy and subsequent surveillance biopsy approximately 1 year later. Outcome measures included change in overall %GP4 and total length GP4 (mm)., Results and Limitations: 61 patients met the inclusion criteria, the median change in total length of GP4 and %GP4 was -0.12 mm (IQR -0.31, 0.09) and -2.5% (IQR -8.6, 0.0), respectively. Excluding the 35 patients with no evidence of GP4 on surveillance biopsy, median change in total GP4 length and %GP4 was 0.19 mm (IQR -0.04, 0.67) and 1.2% (IQR -1.6, 6.6), respectively. Three patients progressed to GG3 disease on surveillance biopsy, one of whom had only a small increase in %GP4. Conversely, an additional 2 patients who did not meet the criterion for GG3 had a large increase (> 1 mm) in total GP4 length., Conclusions: Presence of GG3 disease on surveillance biopsy as a trigger for treatment in men on AS is of questionable use alone; we suggest including other measures that do not depend on a ratio, such as an increase in total GP4 length., Competing Interests: Disclouser All conflicts of interest, including specific financial interests, relations and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment, affiliations, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties filed, received or pending, personal relationships), are listed below: Peter T. Scardino is named on a patent for a statistical method to detect prostate cancer that has been commercialized by OPKO Health (from which he receives royalties and stock options) and chairs the Medical Advisory board of Insightec as an unpaid consultant. Andrew J. Vickers is named on a patent for a statistical method to detect prostate cancer that has been commercialized by OPKO Health (from which he receives royalties and stock options) and has received consulting funds from Insightec and Steba. None of these companies contributed to or directed any of the research reported in this article. The other authors declare no conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback., Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy., Design Setting and Participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center., Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE)., Outcome Measurements and Statistical Analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency., Results and Limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains., Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program., Patient Summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency., (© 2024 The Authors.)

Purpose: There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP., Materials and Methods: An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models., Results: The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR., Conclusions: Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Importance: Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm., Objective: To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM)., Data Sources: PubMed search from 2000 to 2022., Study Selection: Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel., Data Extraction and Synthesis: Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022., Main Outcomes and Measures: Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months)., Results: From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86])., Conclusions and Relevance: Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer. For patients with nonmetastatic CRPC, ADT is continued with or without the addition of certain secondary hormone therapies depending on prostate-specific antigen doubling time. In the mCRPC setting, ADT is continued with the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects.

Objective: To determine if hypogonadism leads to delayed urinary function recovery post-radical prostatectomy (RP) by studying the effect of preoperative factors including age, membranous urethral length, radiation therapy, and Body Mass Index on urinary continence in patients with or without hypogonadism., Materials and Methods: We identified 1209 patients treated by RP with both pretreatment T and post-treatment urinary outcome. We assessed whether there was an association between low preoperative T level (prenoon T ≤ 300 ng/dL) and continence (using ≤1 pad/d) at 6 and 12months post-RP. Patient-reported continence was used when available, otherwise, surgeon-assessed continence was used. Logistic regression models were used, adjusted for age at RP and nerve-sparing status., Results: Median age at RP was 61 (Intraquatile Range (IQR) 56, 66), 92% of patients had at least one nerve spared and 99% were continent at baseline. Continence in patients with low T was nonsignificantly lower at 6months (odds ratio 0.69, 95% confidence interval 0.44, 1.06; P = .10) and nonsignificantly higher at 12months (odds ratio 1.07, 95% confidence interval 0.71, 1.58; P = .8). Sensitivity analyses excluding patients with preoperative metastasis or treated with androgen deprivation therapy (ADT) and including testosterone as a continuous predictor were consistent with the primary analysis; similarly finding no evidence of an association., Conclusion: Although we cannot rule out an effect on early continence, overall the evidence does not suggest that low serum testosterone adversely impacts urinary function recovery after RP. This finding can be used to counsel patients enrolled in neoadjuvant ADT trials or those patients undergoing RP who have had prior ADT, such as in the setting of oligometastatic disease., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

The da Vinci ® Vessel Sealer is a major contributor to the total cost of robot-assisted laparoscopic prostatectomy (RALP). We aimed to assess whether the use of the Vessel Sealer is associated with better surgical outcomes in a population of patients that underwent RALP with lymphadenectomy. We tested whether the use of the Vessel Sealer is associated with the development of lymphocele and/or other surgical outcomes. Most surgeons used the Vessel Sealer in almost all or almost no patients. Thus, to avoid the potential confounding variable of surgeon skill, we performed the initial analyses using data from a single surgeon who changed practice over time, and then using the entire population. Overall, the Vessel Sealer was used in 500 (36%) RALPs. Surgeon 1 performed 492 surgeries, and used the Vessel Sealer in 191 (39%). The Vessel Sealer was not associated with better surgical outcomes in patients operated on by Surgeon 1. The odds ratio for development of lymphocele was 1.95 (95% confidence interval [CI] 0.57-6.75). In the entire population, use of the sealer was significantly associated with a very small reduction of blood loss (22 cc, CI 13-30) but with a 32-min increase in the operating room time (CI 26-37). Use of the Vessel Sealer will have, at best, a very small effect on RALP outcomes that is of highly questionable relevance given its cost. In light of these results, the Vessel Sealer will only be used at our institution in the context of clinical trials., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Active surveillance (AS) is recommended as the preferred treatment for men with low-risk disease. In order to optimize risk stratification and exclude undiagnosed higher-grade disease, most AS protocols recommend a confirmatory biopsy., Objective: We aimed to compare outcomes among men with grade group (GG) 2/3 prostate cancer on initial biopsy with those among men whose disease was initially GG1 but was upgraded to GG2/3 on confirmatory biopsy., Design, Setting, and Participants: We reviewed patients undergoing radical prostatectomy (RP) in two cohorts: "immediate RP group," with GG2/3 cancer on diagnostic biopsy, and "AS group," with GG1 cancer on initial biopsy that was upgraded to GG2/3 on confirmatory biopsy., Outcome Measurements and Statistical Analysis: Probabilities of biochemical recurrence (BCR) and salvage therapy were determined using multivariable Cox regression models with risk adjustment. Risks of adverse pathology at RP were also compared using logistic regression., Results and Limitations: The immediate RP group comprised 4009 patients and the AS group comprised 321 patients. The AS group had lower adjusted rates of adverse pathology (27% vs 35%, p = 0.003). BCR rates were lower in the AS group, although this did not reach conventional significance (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06, p = 0.10) compared with the immediate RP group. Risk-adjusted 1- and 5-yr BCR rates were 4.6% (95% CI 3.0-6.5%) and 10.4% (95% CI 6.9-14%), respectively, for the AS group compared with 6.3% (95% CI 5.6-7.0%) and 20% (95% CI 19-22%), respectively, in the immediate RP group. A nonsignificant association was observed for salvage treatment-free survival favoring the AS group (HR 0.67, 95% CI 0.42, 1.06, p = 0.087)., Conclusions: We found that men with GG1 cancer who were upgraded on confirmatory biopsy tend to have less aggressive disease than men with the same grade found at initial biopsy. These results must be confirmed in larger series before recommendations can be made regarding a more conservative approach in men with upgraded pathology on surveillance biopsy., Patient Summary: We studied men with low-risk prostate cancer who were initially eligible for active surveillance but presented with more aggressive cancer on confirmatory biopsy. We found that outcomes for these men were better than the outcomes for those diagnosed initially with more serious cancer., (Copyright © 2022. Published by Elsevier B.V.)

Background: We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model., Methods: NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus., Results: Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with ≤10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%)., Conclusions: A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A prostate-specific antigen density (PSAd) cutoff of 0.15 ng/ml/cc is a commonly recommended threshold to identify patients with negative prostate magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We were unable to find any study that explicitly examined the properties of this threshold compared with others., Objective: To investigate whether the 0.15 cutoff is justified for selecting patients at risk of harboring high-grade cancer (Gleason score ≥3 + 4) despite negative MRI., Design, Setting, and Participants: A cohort of 8974 prostate biopsies provided by the Prostate Biopsy Collaborative Group (PBCG) was included in the study., Outcome Measurements and Statistical Analysis: Locally weighted scatterplot smoothing was used to investigate whether there was a change in the risk of high-grade cancer around this value. We examined whether the use of this cutoff in patients with negative MRI corresponds to a reasonable threshold probability for a biopsy (defined as a 10% risk of high-grade disease). To do so, we applied the negative likelihood ratio of MRI, calculated from eight studies on prostate MRI, to the risk curve derived from the PBCG., Results and Limitations: There was no discontinuity in the risk of high-grade prostate cancer at a PSAd cutoff of 0.15. This cutoff corresponded to a probability of high-grade disease ranging from 2.6% to 10%, depending on MRI accuracy. Using 10% as threshold probability, the corresponding PSAd cutoff varied between 0.15 and 0.38, with the threshold increasing for greater MRI accuracy. Possible limitations include difference between studies on MRI and the use of ultrasound to measure prostate volume., Conclusions: The 0.15 cutoff to recommend prostate biopsies in patients with negative MRI is justified only under an extreme scenario of poor MRI properties. We recommend a value of at least ≥0.20. Our results suggest the need for future studies to look at how to best identify patients who need prostate biopsies despite negative MRI, likely by using individualized risk prediction., Patient Summary: In this study, we investigated whether the commonly used prostate-specific antigen density cutoff of 0.15 is justified to identify patients with negative magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We found that this cutoff is appropriate only in case of very poor MRI quality, and a higher cutoff (≥0.20) should be used for the average MRI., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Pathologic nodal invasion at prostatectomy is frequently associated with persistently elevated prostate-specific antigen (PSA) and with increased risk of disease recurrence. Management strategies for these patients are poorly defined. We aimed to explore the long-term oncologic outcomes and patterns of disease progression., Methods: We included men treated between 2000 and 2017 who had lymph node invasion at radical prostatectomy and persistently detectable prostate-specific antigen post-prostatectomy. Postoperative imaging and management strategies were collated. Patterns of recurrence and probability of metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were assessed., Results: Among our cohort of 253 patients, 126 developed metastasis. Twenty-five had a positive scan within 6 months of surgery; of these, 15 (60%) had a nodal metastasis, 10 (40%) had a bone metastasis, and 4 (16%) had local recurrence. For metastasis-free survival, 5- and 10-year probabilities were 52% (95% CI 45%, 58%) and 37% (95% CI 28%, 46%), respectively. For prostate cancer-specific survival, 5- and 10-year probabilities were 89% (95% CI 84%, 93%) and 67% (95% CI 57%, 76%), respectively. A total of 221 patients proceeded to hormonal deprivation treatment alone. Ten patients received postoperative radiotherapy., Conclusions: Biochemical persistence in patients with lymph node invasion is associated with high risk of disease progression and reduced prostate cancer-specific survival. Management was hindered by the limitation of imaging modalities utilized during the study period in accurately detecting residual disease. Novel molecular imaging may improve staging and help design a therapeutic strategy adapted to patients' specific needs., (Copyright © 2022. Published by Elsevier Inc.)

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., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel's discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.

Introduction: Our goal was to determine whether zonal origin of anterior dominant prostate cancers is associated with clinical outcome among patients treated with radical prostatectomy., Methods: We investigated the clinical outcomes of 197 patients with previously well-characterized anterior dominant prostatic tumors on radical prostatectomy. Univariable Cox proportional hazards models were used to test for an association between anterior peripheral zone (PZ) or transition zone (TZ) tumor location and clinical outcomes., Results: Zonal origin of anterior dominant tumors: 97/197 (49%) anterior PZ, 70 (36%) TZ, 14 (7%) both zones and 16 (8%) indeterminate zone. Comparing anterior PZ and TZ tumors, there were no significant differences in Grade group, incidence of extraprostatic extension or surgical margin positivity rate. Overall, 19 (9.6%) patients experienced biochemical recurrence (BCR), including 10 with anterior PZ origin and 5 with TZ origin. Median followup time among those without BCR was 9.5 years (IQR 7.2, 12.7). BCR-free survival at 5 and 10 years was 91% and 89% for anterior PZ tumors, and 94% and 92% for TZ tumors, respectively. On univariate analysis, there was no evidence of a difference in time to BCR between anterior PZ and TZ tumor zone of origin (p=0.5)., Conclusions: In this anatomically well-characterized cohort of anterior dominant prostate cancers, long-term BCR-free survival was not significantly associated with zone of origin. Future studies utilizing zone of origin as a parameter should consider separating anterior and posterior PZ localization, as outcomes may differ.