Randomized Trial of Transverse vs Vertical Extraction Site Incision After Robotic Radical Prostatectomy.

PURPOSE: Incisional hernias are a frequent complication following robotic radical prostatectomy. Observational data in men undergoing robotic prostatectomy suggest that transverse closure resulted in lower hernia rates than vertical closure. We sought to compare the incidence of incisional hernia after robotic radical prostatectomy after vertical and transverse extraction site closure. MATERIALS AND METHODS: We conducted a clinically integrated, crossover, cluster randomized trial at a single tertiary referral center (January 2016-September 2021) comparing the rate of hernia after transverse vs vertical extraction site excision in 1356 patients treated with minimally invasive radical prostatectomy. The primary outcome was between-group incidence of incisional hernia within 15 months of prostatectomy defined by physical examination and self-reported patient surveys. RESULTS: Overall, 197 (20%) patients developed an incisional hernia within 15 months, 797 did not have an incisional hernia within this period, and 362 had missing outcome data regarding incisional hernia. We found no significant difference in hernia rates between the 2 incision types (absolute between-group difference 1.8%; 95% CI -3.4%, 6.6%; P = .5) in the primary analysis or in the 3 sensitivity analyses. Notably, because of the inclusive definition of hernia used, these data cannot be used as an estimate of the true prevalence of incisional hernia. CONCLUSIONS: Surgeons should choose the incision and closure approach they are most comfortable with when extracting specimens. Studies of modifications to the surgical technique are best conducted as randomized comparisons, and the clinically integrated, crossover, cluster randomized trial allows large trials to be completed at a single center and at low cost. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407263.

Successful completion of large, low-cost randomized cancer trials at an academic cancer center.

BACKGROUND: Concerns about low accrual have long been a standard part of the discourse on cancer clinical trials, reaching even as far as the news media. Indeed, so many trials are closed before completing accrual that a cottage industry has recently developed creating statistical models to predict trial failure. We previously proposed four methodologic fixes for the current crisis in clinical trials: (1) dramatically reducing the number of eligibility criteria, (2) using data routinely collected in clinical practice for trial endpoints; then lowering barriers to accrual by (3) cluster randomization or (4) staged consent. METHODS: We report our practical experience of applying these fixes to randomized trials at Memorial Sloan Kettering Cancer Center. RESULTS: We have completed seven single-center randomized trials, with several more underway and accruing rapidly, with a total accrual approaching 10,000. Many of the trials have compared surgical interventions, an area where trials have traditionally been hard to complete. Only one of these trials was externally funded. While low costs were possible due to the existing research infrastructure at our institution, such infrastructure is common at major cancer centers. CONCLUSIONS: Further research on innovative clinical trial designs is warranted, particularly in higher-stakes settings, and in trials of medical and radiotherapy interventions.

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.

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.

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.

MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study.

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

Have urinary function outcomes after radical prostatectomy improved over the past decade?

BACKGROUND: Changes in surgical technique and postoperative care that target improvements in functional outcomes are widespread in the literature. Radical prostatectomy (RP) is one such procedure that has seen multiple advances over the past decade. The objective of this study was to leverage RP as an index case to determine whether practice changes over time produced observable improvements in patient-reported outcomes. METHODS: This study analyzed patients undergoing RP by experienced surgeons at a tertiary care center with prospectively maintained patient-reported outcome data from 2008 to 2019. Four patient-reported urinary function outcomes at 6 and 12 months after RP were defined with a validated instrument: good urinary function (domain score ≥ 17), no incontinence (0 pads per day), social continence (≤1 pad per day), and severe incontinence (≥3 pads per day). Multivariable logistic regressions evaluated changes in outcomes based on the surgical date. RESULTS: Among 3945 patients meeting the inclusion criteria, excellent urinary outcomes were reported throughout the decade but without consistent observable improvements over time. Specifically, there were no improvements in good urinary function at 12 months (P = .087) based on the surgical date, and there were countervailing effects on no incontinence (worsening; P = .005) versus severe incontinence (improving; P = .003). Neither approach (open, laparoscopic, or robotic), nor nerve sparing, nor membranous urethral length mediated changes in outcomes. CONCLUSIONS: In a decade with multiple advances in surgical and postoperative care, there was evidence of improvements in severe incontinence, but no measurable improvements across 3 other urinary outcomes. Although worsening disease factors could contribute to the stable observed outcomes, a more systematic approach to evaluating techniques and implementing patient selection and postoperative care advances is needed. LAY SUMMARY: Although there have been advances in radical prostatectomy over the past decade, consistent observable improvements in postoperative incontinence were not reported by patients. To improve urinary function outcomes beyond the current high standard, the approach to studying innovations in surgical technique needs to be changed, and further development of other aspects of prostatectomy care is needed.

Independent validation of a pre-specified four-kallikrein marker model for prediction of adverse pathology and biochemical recurrence.

BACKGROUND: Accurate markers for prostate cancer (PC) risk stratification could aid decision-making for initial management strategies. The 4Kscore has an undefined role in predicting outcomes after radical prostatectomy (RP). METHODS: We included 1476 patients with 4Kscore measured prior to RP at two institutions. The 4Kscore was assessed for prediction of adverse pathology at RP and biochemical recurrence (BCR) relative to a clinical model. We pre-specified that all analyses would be assessed in biopsy Grade Group 1 (GG1) or 2 (GG2) PC patients, separately. RESULTS: The 4Kscore increased discrimination for adverse pathology in all patients (delta area under the receiver operative curve (AUC) 0.009, 95% confidence interval (CI) 0.002, 0.016; clinical model AUC 0.767), driven by GG1 (delta AUC 0.040, 95% CI 0.006, 0.073) rather than GG2 patients (delta AUC 0.005, 95% CI -0.012, 0.021). Adding 4Kscore improved prediction of BCR in all patients (delta C-index 0.014, 95% CI 0.007, 0.021; preop-BCR nomogram C-index 0.738), again with larger changes in GG1 than in GG2. CONCLUSIONS: This study validates prior investigations on the use of 4Kscore in men with biopsy-confirmed PC. Men with GG1 PC and a high 4Kscore may benefit from additional testing to guide treatment selection. Further research is warranted regarding the value of the 4Kscore in men with biopsy GG2 PC.

Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer.

PURPOSE: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. MATERIALS AND METHODS: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. RESULTS: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum %GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. CONCLUSIONS: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.

Association of Family History of Cancer with Clinical and Pathological Outcomes for Prostate Cancer Patients on Active Surveillance.

PURPOSE: The impact of germline mutations associated with hereditary cancer syndromes in patients on active surveillance (AS) for prostate cancer is poorly defined. We examined the association between family history of prostate cancer (FHP) or family history of cancer (FHC) and risk of progression or adverse pathology at radical prostatectomy (RP) in patients on AS. MATERIALS AND METHODS: Patients on AS at a single tertiary-care center between 2000-2019 were categorized by family history. Disease progression was defined as an increase in Gleason grade on biopsy. Adverse pathology was defined as upgrading/upstaging at RP. Multivariable Cox and logistic regression models were used to assess association between family history and time to progression or adverse pathology, respectively. RESULTS: Among 3,211 evaluable patients, 669 (21%) had FHP, 34 (1%) had FHC and 95 (3%) had both; 753 progressed on AS and 481 underwent RP. FHP was associated with increased risk of progression (HR 1.31; 95% CI, 1.11-1.55; p=0.002) but FHC (HR 0.67; 95% CI, 0.30-1.50; p=0.3) or family history of both (HR 1.22; 95% CI, 0.81-1.85; p=0.3) were not. FHP, FHC or both were not associated with adverse pathology at RP (p >0.4). CONCLUSIONS: While FHP was associated with an increased risk of progression on AS, wide confidence intervals render this outcome of unclear clinical significance. FHC was not associated with risk of progression on AS. In the absence of known genetically defined hereditary cancer syndrome, we suggest FHP and/or FHC should not be used as a sole trigger to preclude patients from enrolling on AS.

Characterization of Symptoms after Radical Prostatectomy and Their Relation to Postoperative Complications.

PURPOSE: Many patients will experience symptoms in the initial days after radical prostatectomy (RP), but early patient-reported symptoms have not been well characterized. Our objective was to illustrate the pattern of symptoms experienced after RP and the relation of severe symptoms to postoperative complications. MATERIALS AND METHODS: In 2016, electronic patient-reported symptom monitoring began at our institution's ambulatory surgery center. We retrospectively reviewed patients treated with minimally invasive RP who were sent a daily questionnaire completed using a web interface until postoperative day 10. Severe symptoms automatically generate a "yellow alert," which messages the clinic, while very severe symptoms generate a "red alert," additionally prompting the patient to call. We summarized rates of moderate-to-very severe symptoms and fit local polynomial regressions. We compared rates of 30-day or 90-day complications (grade ≥2) based on the presence of alert symptoms. RESULTS: Of 2,266 men undergoing RP, 1,942 (86%) completed surveys. Among moderate-to-very severe symptom levels, pain (72%) and dyspnea (11%) were most common. Pain, nausea and dyspnea consistently decreased over time; fever and vomiting had a flat pattern. In patients experiencing red-alert symptoms, we observed a higher risk of 30-day complications, but rates were low and differences between groups were nonsignificant (2.9% vs 1.9%; difference 1.1%; 95% CI -1.3-3.5; p=0.3). Results were similar examining 90-day complications. CONCLUSIONS: While symptoms are common after RP, substantial improvements occur over the first 10 days. Severe or very severe symptoms conferred at most a small absolute increase in complication risk, which should be reassuring to patients and clinicians.

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.

The Duration of Antibiotics Prophylaxis at the Time of Catheter Removal after Radical Prostatectomy: Clinically Integrated, Cluster, Randomized Trial.

PURPOSE: Prophylactic antibiotics are routinely given at the time of catheter removal post-radical prostatectomy (RP). The low rate of infectious complications entails that large sample sizes are required for randomized controlled trials, a challenge given the cost of standard randomized controlled trials. We evaluated infectious complications associated with 1 vs 3 days of prophylactic antibiotics at the time of catheter removal post-RP using a novel, clinically integrated trial with randomization at the surgeon level. MATERIALS AND METHODS: Surgeons were cluster randomized for periods of 3 months to prescribe 1-day vs 3-day regimen of prophylactic antibiotics at the time of catheter removal. The primary end point was an infectious complication as routinely captured by nursing phone call within 10 days of catheter removal and defined as positive urine cultures (≥105 CFU) and at least 1 of the following symptoms: fever (>38°C), urgency, frequency, dysuria or suprapubic tenderness. RESULTS: A total of 824 patients were consented and underwent RP with, respectively, 389 and 435 allocated to 1-day and 3-day antibiotics, predominantly ciprofloxacin. Accrual was achieved within 3 years: 95% vs 88% of patients received the allocated 3-day vs 1-day antibiotic regimen. There were 0 urinary tract infections (0%) in the 1-day regimen and 3 urinary tract infections (0.7%) in the 3-day regimen, meeting our prespecified criterion for declaring the 1-day regimen to be noninferior. CONCLUSIONS: A clinically integrated trial using cluster randomization accrued rapidly with no important logistical problems and negligible burden on surgeons. If surgeons choose to prescribe empiric prophylactic antibiotics after catheter removal following RP, then the duration should not exceed 1 day.

Patient accrual and understanding of informed consent in a two-stage consent design.

BACKGROUND: We previously introduced the concept of "two-stage" (or "just-in-time") informed consent for randomized trials with usual care control. We argued that conducting consent in two stages-splitting information about research procedures from information about the experimental intervention-would reduce the decisional anxiety, confusion, and information overload commonly associated with informed consent. We implemented two-stage consent in a low-stakes randomized trial of a mindfulness meditation intervention for procedural distress in patients undergoing prostate biopsy. Here, we report accrual rates and patient understanding of the consent process. METHODS: Patients approached for consent for the biopsy trial were asked to complete the standard "Quality of Informed Consent" questionnaire to assess their knowledge and understanding of the trial. RESULTS: Accrual was excellent with 108 of 110 (98%) patients approached for consent signing first-stage consent. All 51 patients randomized to the experimental arm and who later presented for biopsy signed second-stage consent and received the mindfulness intervention. Quality of Informed Consent data were available for 48 patients assigned to the mindfulness treatment arm and 44 controls. The mean Quality of Informed Consent score was similar in the meditation and control arms with and overall mean of 75 (95% confidence interval = 74-76) for the knowledge section and 86 (95% confidence interval = 81-90) for understanding, comparable to the normative scores of 80 and 88. On further analysis and patient interview, two of the Quality of Informed Consent questions were found to be misleading in the context of a two-stage consent study for a mindfulness intervention. Excluding these questions increased knowledge scores to 88 (95% confidence interval = 87-90). CONCLUSION: We found promising data that two-stage consent facilitated accrual without compromising patient understanding of randomized trials or compliance with allocated treatment. Further research is needed incorporating randomized comparison of two-stage consent to standard consent approaches, measuring patient anxiety and distress as an outcome, using suitable modifications to the Quality of Informed Consent questionnaire and trials with higher stakes.

Risk of Metastasis in Men with Grade Group 2 Prostate Cancer Managed with Active Surveillance at a Tertiary Cancer Center.

PURPOSE: We studied the risk of metastatic prostate cancer development in men with Grade Group 2 disease managed with active surveillance at Memorial Sloan Kettering Cancer Center. MATERIALS AND METHODS: A total of 219 men with Grade Group 2 prostate cancer had disease managed with active surveillance between 2000 and 2017. Biopsy was performed every 2 to 3 years, or upon changes in magnetic resonance imaging, prostate specific antigen level or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival. RESULTS: Median age at diagnosis was 67 years (IQR 61-72), median prostate specific antigen was 5 ng/ml (IQR 4-7) and most patients (69%) had nonpalpable disease. During followup 64 men received treatment, including radical prostatectomy in 36 (56%), radiotherapy in 20 (31%), hormone therapy in 3 (5%) and focal therapy in 5 (8%). Of the 36 patients who underwent radical prostatectomy 32 (89%) had Grade Group 2 disease on pathology and 4 (11%) had Grade Group 3 disease. Treatment-free survival was 61% (95% CI 52-70) at 5 years and 49% (95% CI 37-60) at 10 years. Three men experienced biochemical recurrence, no men had distant metastasis and no men died of prostate cancer during the followup. Median followup was 3.1 years (IQR 1.9-4.9). CONCLUSIONS: Active surveillance appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer treated at a tertiary cancer center. Definitive conclusions await further followup.

Long-Term Outcomes of Active Surveillance for Prostate Cancer: The Memorial Sloan Kettering Cancer Center Experience.

PURPOSE: We report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance at a tertiary cancer center. MATERIALS AND METHODS: A total of 2,907 patients were managed with active surveillance between 2000 and 2017, of whom 2,664 had Grade Group 1 disease. Patients were recommended confirmatory biopsy to verify eligibility and were followed semiannually with prostate specific antigen, digital rectal examination and review of symptoms. Magnetic resonance imaging was increasingly used in recent years. Biopsy was repeated every 2 to 3 years or after a sustained prostate specific antigen increase or changes in magnetic resonance imaging/digital rectal examination. The Kaplan-Meier method was used to estimate probabilities of treatment, progression and development of metastasis. RESULTS: Median patient age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer the treatment-free probability at 5, 10 and 15 years was 76% (95% CI 74-78), 64% (95% CI 61-68) and 58% (95% CI 51-64), respectively. At 5, 10 and 15 years there were 1,146, 220 and 25 men at risk for metastasis, respectively. Median followup for those without metastasis was 4.3 years (95% CI 2.3-6.9). Distant metastasis developed in 5 men. Upon case note review only 2 of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2-2.0) at 10 years. CONCLUSIONS: Active surveillance is a safe strategy over longer followup for appropriately selected patients with Grade Group 1 disease following a well-defined monitoring plan.

Quality improvement initiative to reduce variability and improve stewardship of antimicrobial prophylaxis for transrectal prostate needle biopsy.

PURPOSE: To assess the impact of implementing the recommendations included in the 2014 American Urological Association (AUA) white paper on complications of transrectal prostate needle biopsy (PNB). METHODS: In the outpatient setting of a single tertiary-care institution, prophylactic antibiotic use and rate of infectious complications were compared before and after implementation by nursing of a standardized algorithm to select antibiotic prophylaxis (derived from the recommendations of the AUA white paper). The 584 patients in cohort A (January 2011-January 2012) received antimicrobial prophylaxis at the discretion of the treating physician; 654 patients in cohort B (January 2014-January 2015) received standardized risk-adapted antibiotic prophylaxis. Data on antibiotics administered and infectious complications were analyzed. RESULTS: Fluoroquinolone was the most common prophylactic regimen in both cohorts. In cohort A, 73% of men received a single-drug regimen, although 19 different regimens were utilized with duration of 72 h. In cohort B, 97% received 1 of 4 standardized single-drug antibiotic regimens for duration of 24 h. Infectious complications occurred in 19 men (3.3%) in cohort A, and in 18 men (2.8%) in cohort B (difference - 0.5%; one-sided 95% CI 1.1%). No clinically relevant increase in infectious complication rates was found after implementing this quality improvement initiative. CONCLUSIONS: Use of a standardized risk-adapted approach to select antibiotic prophylaxis for PNB by nursing staff reduced the duration of antimicrobial prophylaxis and number of antibiotic regimens used, without increasing the rate of infectious complications. Our findings validate the current AUA recommendations for antibiotic prophylaxis.

Clinical Usefulness of Total Length of Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer.

PURPOSE: To our knowledge the ideal methodology of quantifying secondary Gleason pattern 4 in men with Grade Group 2/Gleason score 3 + 4 = 7 on biopsy remains unknown. We compared various methods of Gleason pattern 4 quantification and evaluated associations with adverse pathology findings at radical prostatectomy. MATERIALS AND METHODS: A total of 457 men with Grade Group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy at our institution. Only patients with 12 or more reviewed cores were included in analysis. We evaluated 3 methods of quantifying Gleason pattern 4, including the maximum percent of Gleason pattern 4 in any single core, the overall percent of Gleason pattern 4 (Gleason pattern 4 mm/total cancer mm) and the total length of Gleason pattern 4 in mm across all cores. Adverse pathology features at radical prostatectomy were defined as Gleason score 4 + 3 = 7 or greater (Grade Group 3 or greater), and any extraprostatic extension, seminal vesical invasion and/or lymph node metastasis. A training/test set approach and multivariable logistic regression were used to determine whether Gleason pattern 4 quantification methods could aid in predicting adverse pathology. RESULTS: On multivariable analysis all Gleason pattern 4 quantification methods were significantly associated with an increased risk of adverse pathology (p <0.0001) and an increased AUC beyond the base model. The largest AUC increase was 0.044 for the total length of Gleason pattern 4 (AUC 0.728, 95% CI 0.663-0.793). Decision curve analysis demonstrated an increased clinical net benefit with the addition of Gleason pattern 4 quantification to the base model. The total length of Gleason pattern 4 clearly provided the largest net benefit. CONCLUSIONS: Our findings support the inclusion of Gleason pattern 4 quantification in the pathology reports and risk prediction models of patients with Grade Group 2/Gleason score 3 + 4 = 7 prostate cancer. The total length of Gleason pattern 4 across all cores provided the strongest benefit to predict adverse pathology features.

SPARED Collaboration: Patient Selection for Partial Gland Ablation in Men with Localized Prostate Cancer.

PURPOSE: The SPARED CRN (Study of Prostate Ablation Related Energy Devices Coordinated Registry Network) is a private-public partnership between academic and community urologists, the FDA (U.S. Food and Drug Administration), the Medical Device Epidemiology Network and device manufacturers to examine the safety and effectiveness of technologies for partial gland ablation in men with localized prostate cancer. MATERIALS AND METHODS: We report on a recent workshop at the FDA with thought leaders to discuss a critical framework for partial gland ablation, focusing on patient selection, surgical planning, followup, study design and appropriate comparators in terms of adverse events and cancer control outcomes. We summarize salient points from experts in urology, oncology and epidemiology that were presented and discussed in an open forum. RESULTS: Given the challenges in achieving patient and physician equipoise to perform a randomized trial, as well as an inherent paradigm shift when comparing partial gland ablation (inability to assess prostate specific antigen recurrence) to whole gland treatments, the group focused on objective performance criteria and goals as a platform to guide the creation of single arm studies in the SPARED CRN. CONCLUSIONS: This summit lays the foundation for prospective, multi-center data collection and evaluation of novel medical devices and drug/device combinations for partial gland ablation.

The Influence of Background Signal Intensity Changes on Cancer Detection in Prostate MRI.

OBJECTIVE: The objective of this study was to develop a scoring system for background signal intensity changes or prostate homogeneity on prostate MRI and to assess these changes' influence on cancer detection. MATERIALS AND METHODS: This institutional review board-approved, HIPAA-compliant, retrospective study included 418 prostate MRI examinations in 385 men who subsequently underwent MRI-guided biopsy. The Likert score for suspicion of cancer assigned by the primary radiologist was extracted from the original report, and histopathologic work-up of the biopsy cores served as the reference standard. Two readers assessed the amount of changes on T2-weighted sequences and assigned a predefined prostate signal-intensity homogeneity score of 1-5 (1 = poor, extensive changes; 5 = excellent, no changes). The sensitivity and specificity of Likert scores for detection of prostate cancer and clinically significant cancer (Gleason score ≥ 3+4) were estimated in and compared between subgroups of patients with different signal-intensity homogeneity scores (≤ 2, 3, and ≥ 4). RESULTS: Interreader agreement on signal-intensity homogeneity scores was substantial (κ = 0.783). Sensitivity for prostate cancer detection increased when scores were better (i.e., higher) (reader 1, from 0.41 to 0.71; reader 2, from 0.53 to 0.73; p ≤ 0.007, both readers). In the detection of significant cancer (Gleason score ≥ 3+4), sensitivity also increased with higher signal-intensity scores (reader 1, from 0.50 to 0.82; reader 2, from 0.63 to 0.86; p ≤ 0.028), though specificity decreased significantly for one reader (from 0.67 to 0.38; p = 0.009). CONCLUSION: Background signal-intensity changes on T2-weighted images significantly limit prostate cancer detection. The proposed scoring system could improve the standardization of prostate MRI reporting and provide guidance for applying prostate MRI results appropriately in clinical decision-making.