Provider Perceptions of an Electronic Health Record Prostate Cancer Screening Tool.

OBJECTIVES: We conducted a focus group to assess the attitudes of primary care physicians (PCPs) toward prostate-specific antigen (PSA)-screening algorithms, perceptions of using decision support tools, and features that would make such tools feasible to implement. METHODS: A multidisciplinary team (primary care, urology, behavioral sciences, bioinformatics) developed the decision support tool that was presented to a focus group of 10 PCPs who also filled out a survey. Notes and audio-recorded transcripts were analyzed using Thematic Content Analysis. RESULTS: The survey showed that PCPs followed different guidelines. In total, 7/10 PCPs agreed that engaging in shared decision-making about PSA screening was burdensome. The majority (9/10) had never used a decision aid for PSA screening. Although 70% of PCPs felt confident about their ability to discuss PSA screening, 90% still felt a need for a provider-facing platform to assist in these discussions. Three major themes emerged: (1) confirmatory reactions regarding the importance, innovation, and unmet need for a decision support tool embedded in the electronic health record; (2) issues around implementation and application of the tool in clinic workflow and PCPs' own clinical bias; and (3) attitudes/reflections regarding discrepant recommendations from various guideline groups that cause confusion. CONCLUSION: There was overwhelmingly positive support for the need for a provider-facing decision support tool to assist with PSA-screening decisions in the primary care setting. PCPs appreciated that the tool would allow flexibility for clinical judgment and documentation of shared decision-making. Incorporation of suggestions from this focus group into a second version of the tool will be used in subsequent pilot testing.

A Provider-Facing Decision Support Tool for Prostate Cancer Screening in Primary Care: A Pilot Study.

OBJECTIVES: Our objective was to pilot test an electronic health record-embedded decision support tool to facilitate prostate-specific antigen (PSA) screening discussions in the primary care setting. METHODS: We pilot-tested a novel decision support tool that was used by 10 primary care physicians (PCPs) for 6 months, followed by a survey. The tool comprised (1) a risk-stratified algorithm, (2) a tool for facilitating shared decision-making (Simple Schema), (3) three best practice advisories (BPAs: <45, 45-75, and >75 years), and (4) a health maintenance module for scheduling automated reminders about PSA rescreening. RESULTS: All PCPs found the tool feasible, acceptable, and clear to use. Eight out of ten PCPs reported that the tool made PSA screening conversations somewhat or much easier. Before using the tool, 70% of PCPs felt confident in their ability to discuss PSA screening with their patient, and this improved to 100% after the tool was used by PCPs for 6 months. PCPs found the BPAs for eligible (45-75 years) and older men (>75 years) more useful than the BPA for younger men (<45 years). Among the 10 PCPs, 60% found the Simple Schema to be very useful, and 50% found the health maintenance module to be extremely or very useful. Most PCPs reported the components of the tool to be at least somewhat useful, with 10% finding them to be very burdensome. CONCLUSION: We demonstrated the feasibility and acceptability of the tool, which is notable given the marked low acceptance of existing tools. All PCPs reported that they would consider continuing to use the tool in their clinic and were likely or very likely to recommend the tool to a colleague.

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.

Implementation and Validation of an Automated, Longitudinal Robotic Surgical Evaluation and Feedback Program at a High-volume Center and Impact on Training.

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.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: a clinically integrated randomized controlled trial with 2-staged consent.

OBJECTIVES: Many patients experience pain, anxiety, and discomfort with prostate biopsy, which may discourage enrollment in active surveillance programs or follow-up biopsy. Guided meditation can significantly reduce pain and anxiety during percutaneous biopsy. We sought to evaluate the effectiveness of a brief mind-body intervention on patient-reported outcomes after prostate biopsy. METHODS AND MATERIALS: We performed a clinically-integrated randomized controlled trial of a brief mind-body intervention during biopsy compared to usual care at a single tertiary care center from 2018 to 2022. All patients offered transrectal ultrasound-guided prostate biopsy in the clinic with local anesthesia were eligible for enrollment. This clinically integrated trial was conducted simultaneously with a randomized controlled trial of 1-stage and 2-stage consent. The primary outcome was patient-reported pain, anxiety, discomfort, and tolerability on a visual-analog scale (0-10). A 15% improvement was prespecified as clinically relevant. We compared the proportion of men in each arm reporting a severe score (7-10) on any of the 4 scales using Fisher's exact test and then compared means for each scale separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. RESULTS: Of 263 eligible patients, 238 enrolled (119 per arm). One hundred seventy-two (72%) enrolled with 2-stage consent. A total of 37/94 (39%) and 38/102 (37%) patients randomized to usual care and intervention, respectively, reported severe scores in any of the 4 domains, a difference of 2.1% (95% confidence interval [CI] -13, 17%, P = 0.8). There was no evidence of a difference in mean postbiopsy anxiety (P = 0.3), discomfort (P = 0.09), pain (P = 0.4) or tolerability scores (P = 0.2). CONCLUSIONS: A clinically meaningful benefit for this brief mind-body intervention during prostate biopsy is unlikely. Robust patient enrollment is feasible using 2-stage consent.

The oncologic risk of magnetic resonance imaging-targeted and systematic cores in patients treated with radical prostatectomy.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRI-biopsy) detects high-Grade Group (GG) prostate cancers not identified by systematic biopsy (S-biopsy). However, questions have been raised whether cancers detected by MRI-biopsy and S-biopsy, grade-for-grade, are of equivalent oncologic risk. The authors evaluated the relative oncologic risk of GG diagnosed by S-biopsy and MRI-biopsy. METHODS: This was a retrospective analysis of all patients who had both MRI-biopsy and S-biopsy and underwent with prostatectomy (2014-2022) at Memorial Sloan Kettering Cancer Center. Three logistic regression models were used with adverse pathology as the primary outcome (primary pattern 4, any pattern 5, seminal vesicle invasion, or lymph node involvement). The first model included the presurgery prostate-specific antigen level, the number of positive and negative S-biopsy cores, S-biopsy GG, and MRI-biopsy GG. The second model excluded MRI-biopsy GG to obtain the average risk based on S-biopsy GG. The third model excluded S-biopsy GG to obtain the risk based on MRI-biopsy GG. A secondary analysis using Cox regression evaluated the 12-month risk of biochemical recurrence. RESULTS: In total, 991 patients were identified, including 359 (36%) who had adverse pathology. MRI-biopsy GG influenced oncologic risk compared with S-biopsy GG alone (p < .001). However, if grade was discordant between biopsies, then the risk was intermediate between grades. For example, the average risk of advanced pathology for patients who had GG2 and GG3 on S-biopsy was 19% and 66%, respectively, but the average risk was 47% for patients who had GG2 on S-biopsy and patients who had GG3 on MRI-biopsy. The equivalent estimates for 12-month biochemical recurrence were 5.8%, 15%, and 10%, respectively. CONCLUSIONS: The current findings cast doubt on the practice of defining risk group based on the highest GG. Because treatment algorithms depend fundamentally on GG, further research is urgently required to assess the oncologic risk of prostate tumors depending on detection technique. PLAIN LANGUAGE SUMMARY: Using magnetic resonance imaging (MRI) to help diagnose prostate cancer can help identify more high-grade cancers than using a systematic template biopsy alone. However, we do not know if high-grade cancers diagnosed with the help of an MRI are as dangerous to the patient as high-grade cancers diagnosed with a systematic biopsy. We examined all of our patients who had an MRI biopsy and a systematic biopsy and then had their prostates removed to find out if these patients had risk factors and signs of aggressive cancer (cancer that spread outside the prostate or was very high grade). We found that, if there was a difference in grade between the systematic biopsy and the MRI-targeted biopsy, the risk of aggressive cancer was between the two grades.

A randomized comparison of two-stage versus traditional one-stage consent for a low-stakes randomized trial.

BACKGROUND/AIMS: It has been proposed that informed consent for randomized trials should be split into two stages, with the purported advantage of decreased information overload and patient anxiety. We compared patient understanding, anxiety and decisional quality between two-stage and traditional one-stage consent. METHODS: We approached patients at an academic cancer center for a low-stakes trial of a mind-body intervention for procedural distress during prostate biopsy. Patients were randomized to hear about the trial by either one- or two-stage consent (n = 66 vs n = 59). Patient-reported outcomes included Quality of Informed Consent (0-100); general and consent-specific anxiety and decisional conflict, burden, and regret. RESULTS: Quality of Informed Consent scores were non-significantly superior for two-stage consent, by 0.9 points (95% confidence interval = -2.3, 4.2, p = 0.6) for objective and 1.1 points (95% CI = -4.8, 7.0, p = 0.7) for subjective understanding. Differences between groups for anxiety and decisional outcomes were similarly small. In a post hoc analysis, consent-related anxiety was lower among two-stage control patients, likely because scores were measured close to the time of biopsy in the two-stage patients receiving the experimental intervention. CONCLUSION: Two-stage consent maintains patient understanding of randomized trials, with some evidence of lowered patient anxiety. Further research is warranted on two-stage consent in higher-stakes settings.

Patterns of immune equilibrium and escape in indolent and progressing tumors.

By comparing indolent/slowly progressing with aggressive/rapidly progressing tumor types, Pandey et al. identify human evidence of immune equilibrium in indolent tumors and immune escape in progressing tumors, suggesting a link between these mechanisms and the epidemiologic phenomenon of overdiagnosis.

Protocol of a multicentre randomised controlled trial assessing transperineal prostate biopsy to reduce infectiouscomplications.

INTRODUCTION: Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer. METHODS AND ANALYSIS: We will perform a multicentre, prospective randomised clinical trial to compare transperineal versus transrectal prostate biopsy for elevated prostate-specific antigen in the first biopsy, prior negative biopsy and active surveillance biopsy setting. Prostate MRI will be performed prior to biopsy, and targeted biopsy will be conducted for suspicious MRI lesions in addition to systematic biopsy (12 cores). Approximately 1700 men will be recruited and randomised in a 1:1 ratio to transperineal versus transrectal biopsy. A streamlined design to collect data and to determine trial eligibility along with the two-stage consent process will be used to facilitate subject recruitment and retention. The primary outcome is postbiopsy infection, and secondary outcomes include other adverse events (bleeding, urinary retention), pain/discomfort/anxiety and critically, detection of non-low-grade (grade group ≥2) prostate cancer. ETHICS AND DISSEMINATION: The Institutional Review Board of the Biomedical Research Alliance of New York approved the research protocol (protocol number #18-02-365, approved 20 April 2020). The results of the trial will be presented at scientific conferences and published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04815876.

Does a brief surgeon training in negotiation theory principles decrease rates of contralateral prophylactic mastectomy?

PURPOSE: Despite the lack of any oncologic benefit, contralateral prophylactic mastectomy (CPM) use among women with unilateral breast cancer is increasing. This patient-driven trend is influenced by fear of recurrence and desire for peace of mind. Traditional educational strategies have been ineffective in reducing CPM rates. Here we employ training in negotiation theory strategies for counseling and determine the effect on CPM rates. METHODS: In consecutive patients with unilateral breast cancer treated with mastectomy from 05/2017 to 12/2019, we examined CPM rates before and after a brief surgeon training in negotiation skills. This comprised a systematic framework for patient counseling utilizing early setting of the default option, leveraging social proof, and framing. RESULTS: Among 2144 patients, 925 (43%) were treated pre-training and 744 (35%) post-training. Those treated in the 6-month transition period were excluded (n = 475, 22%). Median patient age was 50 years; most patients had T1-T2 (72%), N0 (73%), and estrogen receptor-positive (80%) tumors of ductal histology (72%). The CPM rate was 47% pre-training versus 48% post-training, with an adjusted difference of -3.7% (95% CI -9.4 to 2.1, p = 0.2). In a standardized self-assessment survey, all 15 surgeons reported a high baseline use of negotiation skills and no significant change in conversational difficulty with the structured approach. CONCLUSION: Brief surgeon training did not affect self-reported use of negotiation skills or reduce CPM rates. The choice of CPM is a highly individual decision influenced by patient values and decision styles. Further research to identify effective strategies to minimize surgical overtreatment with CPM is needed.

Patient Perceptions of a Decision Support Tool for Men with Localized Prostate Cancer.

Purpose. To evaluate patient perceptions of a Web-based decision aid for the treatment of localized prostate cancer. Methods. We assessed patient perceptions of a multicomponent, Web-based decision aid with a preference elicitation/values clarification exercise using adaptive conjoint analysis, the generation of a summary report, and provision of information about localized prostate cancer treatment options. Using a think-aloud approach, we conducted 21 cognitive interviews with prostate cancer patients presented with the decision aid prior to seeing their urologist. Thematic content analysis was used to examine patient perceptions of the tool's components and content prior to engaging in shared decision making with their clinician. Results. Five themes were identified: 1) patients had some negative emotional reactions to the tool, pointing out what they perceived to be unnecessarily negative framing and language used; 2) patients were forced to stop and think about preferences while going through the tool and found this deliberation to be useful; 3) patients were confused by the tool; 4) patients tried to discern the intent of the conjoint analysis questions; and 5) there was a disconnect between patients' negative reactions while using the tool and a contrasting general satisfaction with the final "values profile" created by the tool. Conclusions. Studies are needed to explore the disconnect between patients' expressing negative reactions while going through some components of decision aids but satisfaction with the final output. In particular, we hypothesize that this effect might be explained by cognitive biases such as choice-supportive bias, hindsight bias, and the "IKEA effect." This is one of the first projects to elicit patient reactions while they were completing a decision aid, and we recommend further similar, qualitative postprocess evaluation studies. Highlights: We explored perceptions of a decision aid with education about localized prostate cancer treatment and preference elicitation using adaptive conjoint analysis.Patients found the tool useful but were also confused by it, tried to discern the intent of the questions, and expressed negative emotional reactions.In particular, there was a disconnect between patients' negative reactions while using the tool and general satisfaction with the final values profile generated by the tool, which is an area for future research.

Thermal Partial Prostate Ablation for Intermediate- and High-risk Prostate Cancer: Con.

Thermal partial-gland ablation (TPGA) is a promising treatment option for patients with prostate cancer (PCa) that has an excellent side-effect profile. However, the literature on TPGA in high-risk PCa is not robust enough to discount the risk of undertreatment and understaging in this population. Future studies, especially with incorporation of advanced imaging to better select patients, are necessary to understand the safety and efficacy of TPGA in high-risk disease.

Oncologic outcomes of patients with lymph node invasion at prostatectomy and post-prostatectomy biochemical persistence.

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.

Outcomes of Grade Group 2 and 3 Prostate Cancer on Initial Versus Confirmatory Biopsy: Implications for Active Surveillance.

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.

Long-term Health-related Quality of Life in Patients on Active Surveillance for Prostate Cancer: A Systematic Review.

CONTEXT: Active surveillance (AS) represents the preferred treatment option in patients with low-risk prostate cancer. Optimised patient selection has enabled more patients to be managed with AS for a longer time. Thus, there is growing interest in its effect on long-term quality of life compared with interventional management. OBJECTIVE: To perform a systematic review evaluating the long-term patient-reported outcomes regarding mental health, and sexual and urinary function in patients on AS. EVIDENCE ACQUISITION: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We included series assessing validated patient-reported outcomes of health-related quality of life, and sexual and urinary function in AS patients followed up for at least 5 yr. EVIDENCE SYNTHESIS: Our search yielded 1854 citations, including 19 papers involving 3643 patients on AS, 14 651 patients receiving surgery or radiotherapy, and 2478 controls without prostate cancer. In ten studies, major differences were observed in sexual and urinary symptoms between groups, such as better sexual function and fewer irritative urinary symptoms in patients on AS, though overall functional outcomes were comparable. In all studies, health-related quality of life for patients on AS was better than, or similar to, that for patients who had undergone surgery or radiotherapy and comparable with that for individuals without cancer. CONCLUSIONS: We observed differences in specific functional outcomes between patients on AS and surgery or radiotherapy, ≥5 yr after treatment. Patients on AS reported good quality of life, similar to that in individuals without prostate cancer. AS should continue to be a recommended management strategy for appropriately selected patients. PATIENT SUMMARY: Active surveillance is an accepted pathway for patients with low-risk localised prostate cancer. Previous literature has shown that it did not negatively affect short-term quality of life. This review finds that long-term quality of life for these patients is similar to that for people without prostate cancer.

Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer.

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.

Social ecological influences on treatment decision-making in men diagnosed with low risk, localised prostate cancer.

OBJECTIVE: Individuals diagnosed with low risk, localised prostate cancer (PCa) face a difficult decision between active surveillance (AS) and definitive treatment. We aimed to explore perceived influences on treatment decision-making from the patient and partner's perspectives. METHODS: Patients (and partners) who met AS criteria and had chosen their treatment were recruited. Semi-structured individual interviews were conducted via telephone to explore experiences of diagnosis, impact on patient lifestyle, experiences with physicians, treatment preferences/choice, treatment information understanding and needs, and overall decision-making process. Interviews were audio recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. RESULTS: Twenty-four male patients (18 chose AS) and 12 female partners participated. Five themes relating to social-ecological influences on treatment choice were identified: (1) partner support and direct influence on patient treatment choice, (2) patient and partner vicarious experiences may influence treatment decisions, (3) the influence of the patient's life circumstances, (4) disclosing to wider social networks: friends, family, and co-workers, and (5) the importance of a good relationship and experience with physicians. Additionally, two themes were identified relating to information patients and partners received about the treatment options during their decision-making process. CONCLUSIONS: A range of individual and social influences on treatment decision-making were reported. Physicians providing treatment recommendations should consider and discuss the patient and partner's existing beliefs and treatment preferences and encourage shared decision-making. Further research on treatment decision-making of partnered and non-partnered PCa patients is required. We recommend research considers social ecological factors across the personal, interpersonal, community, and policy levels.

Active Surveillance for Men Younger than 60 Years or with Intermediate-risk Localized Prostate Cancer. Descriptive Analyses of Clinical Practice in the Movember GAP3 Initiative.

Background: Active surveillance (AS) is a management option for men diagnosed with low-risk prostate cancer. Opinions differ on whether it is safe to include young men (≤60 yr) or men with intermediate-risk disease. Objective: To assess whether reasons for discontinuation, treatment choice after AS, and adverse pathology at radical prostatectomy (RP; N1, or ≥GG3, or ≥pT3) differ for men ≤60 yr or those with European Association of Urology (EAU) intermediate-risk disease from those for men >60 yr or those with EAU low-risk disease. Design setting and participants: We analyzed data from 5411 men ≤60 yr and 14 959 men >60 yr, 14 064 men with low-risk cancer, and 2441 men with intermediate-risk cancer, originating from the GAP3 database (21 169 patients/27 cohorts worldwide). Outcome measurements and statistical analysis: Cumulative incidence curves were used to estimate the rates of AS discontinuation and treatment choice. Results and limitations: The probability of discontinuation of AS due to disease progression at 5 yr was similar for men aged ≤60 yr (22%) and those >60 yr (25%), as well as those of any age with low-risk disease (24%) versus those with intermediate-risk disease (24%). Men with intermediate-risk disease are more prone to discontinue AS without evidence of progression than men with low-risk disease (at 1/5 yr: 5.9%/14.2% vs 2.0%/8.8%). Adverse pathology at RP was observed in 32% of men ≤60 yr compared with 36% of men >60 yr (p = 0.029), and in 34% with low-risk disease compared with 40% with intermediate-risk disease (p = 0.048). Conclusions: Our descriptive analysis of AS practices worldwide showed that the risk of progression during AS is similar across the age and risk groups studied. The proportion of adverse pathology was higher among men >60 yr than among men ≤60 yr. These results suggest that men ≤60 yr and those with EAU intermediate-risk disease should not be excluded from opting for AS as initial management. Patient summary: Data from 27 international centers reflecting daily clinical practice suggest that younger men or men with intermediate-risk prostate cancer do not hold greater risk for disease progression during active surveillance.