Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Comparing Patient-reported Functional Outcomes After Radical Prostatectomy in Historical and Contemporary Practice.

PURPOSE: Modifications to surgical technique, particularly the widespread adoption of robotic surgery, have been proposed to improve functional recovery after prostate cancer surgery. However, rigorous comparison of men in historical vs contemporary practice to evaluate the cumulative effect of these changes on urinary and sexual function after radical prostatectomy is lacking. MATERIALS AND METHODS: We compared prospectively collected patient-reported urinary and sexual function from historical (PROSTQA [Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment study], n=235) and contemporary (MUSIC-PRO [Michigan Urological Surgery Improvement Collaborative Patient Reported Outcome] registry, n=1,215) cohorts at the University of Michigan to understand whether modern techniques have resulted in functional improvements for men undergoing prostate cancer surgery. RESULTS: We found significant differences in baseline function, with better urinary (median [IQR]; 100 [93.8-100] vs 93.8 [85.5-100], P < .001) and sexual scores (median [IQR]; 83.3 [66.7-100] vs 74.4 [44.2-87.5], P < .001) prior to treatment in PROSTQA compared to MUSIC-PRO patients, respectively. There was no statistically significant difference in the pattern of urinary incontinence recovery after surgery from 6-24 months between groups (P = .14). However, men in the contemporary MUSIC-PRO group did have significantly better recovery of sexual function compared to men in the historical PROSTQA group (P < .0001). Further, we found that contemporary practice consists of men with more unfavorable demographic and clinical characteristics compared to historical practice. CONCLUSIONS: Our results demonstrate that the widespread alterations in prostate cancer surgery over the past 2 decades have yielded improvements in sexual, but not urinary, function recovery.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle Invasive Bladder Cancer.

PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

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.

Development of a Nationally Representative Coordinated Registry Network for Prostate Ablation Technologies.

PURPOSE: The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. MATERIALS AND METHODS: A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. RESULTS: The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF-5 (International Index of Erectile Function-5), the I-PSS (International Prostate Symptom Score), the EPIC-26 (Expanded Prostate Cancer Index Composite-26) and the MSHQ-EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. CONCLUSIONS: A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

Cost-effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer.

OBJECTIVE: To determine how best to use magnetic resonance imaging (MRI) and targeted MRI/ultrasonography fusion biopsy for early detection of prostate cancer (PCa) in men with elevated prostate-specific antigen (PSA) concentrations and whether it can be cost-effective. METHODS: A Markov model of PCa onset and progression was developed to estimate the health and economic consequences of PCa screening with MRI. Patients underwent PSA screening from ages 55 to 69 years. Patients with elevated PSA concentrations (>4 ng/mL) underwent MRI, followed by targeted fusion or combined (standard + targeted fusion) biopsy on positive MRI, and standard or no biopsy on negative MRI. Prostate Imaging Reporting and Data System (PI-RADS) score on MRI was used to determine biopsy decisions. Deaths averted, quality-adjusted life-years (QALYs), cost and incremental cost-effectiveness ratio (ICER) were estimated for each strategy. RESULTS: With a negative MRI, standard biopsy was more expensive and had lower QALYs than performing no biopsy. The optimum screening strategy (ICER $23 483/QALY) recommended combined biopsy for patients with PI-RADS score ≥3 and no biopsy for patients with PI-RADS score <3, and reduced the number of screening biopsies by 15%. Threshold analysis suggests MRI continues to be cost-effective when the sensitivity and specificity of MRI and combined biopsy are simultaneously reduced by 19 percentage points. CONCLUSIONS: Our analysis suggests MRI followed by targeted MRI/ultrasonography fusion biopsy can be a cost-effective approach to the early detection of PCa.

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

Functional Outcomes Following Nerve Sparing Prostatectomy Augmented with Seminal Vesicle Sparing Compared to Standard Nerve Sparing Prostatectomy: Results from a Randomized Controlled Trial.

PURPOSE: Seminal vesicle sparing may reduce the risk of neurovascular bundle injury and improve functional outcomes after prostatectomy. While several observational studies have shown better functional outcomes following seminal vesicle sparing approaches, evidence from randomized trials is lacking. We performed a randomized controlled trial comparing functional and cancer control outcomes between nerve sparing prostatectomy augmented with seminal vesicle sparing and standard nerve sparing prostatectomy. MATERIALS AND METHODS: A total of 140 men with early stage prostate cancer were enrolled in a randomized phase II trial comparing nerve sparing prostatectomy augmented with seminal vesicle sparing to standard nerve sparing prostatectomy. Patient reported sexual and urinary functional scores were assessed prior to surgery, and 6 and 12 months postoperatively. Surgical margin status and prostate specific antigen recurrence were evaluated as secondary outcomes. RESULTS: There were no differences in sexual or urinary function scores after surgery between the study groups. The median urinary incontinence domain score was 92 in the nerve sparing group and 87.5 in the nerve plus seminal vesicle sparing group at 12 months (p = 0.77). Median sexual function domain scores were 73.7 in the nerve sparing group and 77.1 in the nerve sparing plus seminal vesicle sparing group at 12 months (p = 0.29). Margin status and 12-month biochemical recurrence were similar in the groups. CONCLUSIONS: Recovery of continence and sexual function was similar between the groups in this randomized controlled trial. Seminal vesicle sparing did not negatively affect margin status or 12-month biochemical (prostate specific antigen) recurrence. These results suggest limited usefulness of seminal vesicle sparing prostatectomy.

Development and Validation of an Objective Scoring Tool for Robot-Assisted Radical Prostatectomy: Prostatectomy Assessment and Competency Evaluation.

PURPOSE: Comprehensive training and skill acquisition by urological surgeons are vital to optimize surgical outcomes and patient safety. We sought to develop and validate PACE (Prostatectomy Assessment and Competence Evaluation), an objective and procedure specific tool to assess the quality of robot-assisted radical prostatectomy. MATERIALS AND METHODS: Development and content validation of PACE was performed by deconstructing robot-assisted radical prostatectomy into 7 key domains utilizing the Delphi methodology. Reliability and construct validation were then assessed using de-identified videos performed by practicing surgeons and fellows. Consensus for each domain was defined as achieving a content validity index of 0.75 or greater. Reliability was assessed by the intraclass correlation and construct validation using a mixed linear model accounting for multiple ratings on the same video. RESULTS: After 3 rounds consensus was reached on wording, relevance of the skills assessed and concordance between the score assigned and the skill assessed. An intraclass correlation of 0.4 or greater was achieved for all domains. The expert group outperformed trainees in all domains but reached statistical significance in bladder drop (4.5 vs 3.4, p = 0.002), preparation of the prostate (4.4 vs 3.2, p <0.0001), seminal vesicle and posterior plane dissection (8.3 vs 6.8, p = 0.03), and neurovascular bundle preservation (4.1 vs 2.4, p <0.0001). Limitations included the lack of assessment of other key skills such as communication and decision making. CONCLUSIONS: PACE is a structured, procedure specific and reliable tool that objectively measures surgical performance during robot-assisted radical prostatectomy. It can differentiate different levels of expertise and provide structured feedback to customize training and surgical quality improvement.

Anatomical patterns of recurrence following biochemical relapse after post-prostatectomy salvage radiation therapy: a multi-institutional study.

OBJECTIVES: To characterise the frequency and detailed anatomical sites of failure for patients receiving post-radical prostatectomy (RP) salvage radiation therapy (SRT). PATIENTS AND METHODS: A multi-institutional retrospective study was performed on 574 men who underwent SRT between 1986 and 2013. Anatomical recurrence patterns were classified as lymphotrophic (lymph nodes only), osteotrophic (bone only), or multifocal if both were present. Isolated first failure sites were defined as sites of initial clinically detected recurrence that remained isolated for at least 3 months. RESULTS: The median follow-up after SRT was 6.8 years. The 8-year rates of local, regional, and distant failure for patients undergoing SRT were 2%, 6%, and 21%, respectively. Of the 22% men (128 of 574) who developed a clinically detectable recurrence, 17%, 50%, and 31% were lymphotrophic, osteotrophic, and multifocal, respectively. The trophic nature of metastases was prognostic for distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS); the 10-year rates of DMFS were 18%, 5%, and 7% (P < 0.01), and PCSS were 78%, 68%, and 56% (P < 0.01), for lymphotrophic, osteotrophic, and multifocal failure patterns, respectively. CONCLUSIONS: We demonstrate that trophism for metastatic site has significant prognostic impact on PCSS in men treated with SRT. Radiographic local failure is an uncommon event after SRT when compared to historical data of patients treated with surgery monotherapy. However, distant failure remains a challenge in this patient population and warrants further therapeutic investigation.

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

Age, Gender and R.E.N.A.L. Nephrometry Score do not Improve the Accuracy of a Risk Stratification Algorithm Based on Biopsy and Mass Size for Assigning Surveillance versus Treatment of Renal Tumors.

PURPOSE: A previously published risk stratification algorithm based on renal mass biopsy and radiographic mass size was useful to designate surveillance vs the need for immediate treatment of small renal masses. Nonetheless, there were some incorrect assignments, most notably when renal mass biopsy indicated low risk malignancy but final pathology revealed high risk malignancy. We studied other factors that might improve the accuracy of this algorithm. MATERIALS AND METHODS: For 202 clinically localized small renal masses in a total of 200 patients with available R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching main renal artery or vein and location relative to polar lines) nephrometry score, preoperative renal mass biopsy and final pathology we assessed the accuracy of management assignment (surveillance vs treatment) based on the previously published risk stratification algorithm as confirmed by final pathology. Logistic regression was used to determine whether other factors (age, gender, R.E.N.A.L. score, R.E.N.A.L. score components and nomograms based on R.E.N.A.L. score) could improve assignment. RESULTS: Of the 202 small renal masses 53 (26%) were assigned to surveillance and 149 (74%) were assigned to treatment by the risk stratification algorithm. Of the 53 lesions assigned to surveillance 25 (47%) had benign/favorable renal mass biopsy histology while in 28 (53%) intermediate renal mass biopsy histology showed a mass size less than 2 cm. Nine of these 53 masses (17%) were incorrectly assigned to surveillance in that final pathology indicated the need for treatment (ie intermediate histology and a mass greater than 2 cm or unfavorable histology). Final pathology confirmed a correct assignment in all 149 masses assigned to treatment. None of the additional parameters assessed improved assignment with statistical significance. CONCLUSIONS: Age, gender, R.E.N.A.L. nephrometry score, R.E.N.A.L. score components and nomograms or combinations of these factors do not improve the predictive performance of a small renal mass management risk stratification algorithm based on renal mass biopsy and radiographic mass size.

A 10-Item Checklist Improves Reporting of Critical Procedural Elements during Transurethral Resection of Bladder Tumor.

PURPOSE: Previous studies have demonstrated significant variation in recurrence rates after transurethral resection of bladder tumor, likely due to differences in surgical quality. We sought to create a framework to define, measure and improve the quality of transurethral resection of bladder tumor using a surgical checklist. MATERIALS AND METHODS: We formed a multi-institutional group of urologists with expertise with bladder cancer and identified 10 critical items that should be performed during every high quality transurethral bladder tumor resection. We prospectively implemented a 10-item checklist into practice and reviewed the operative reports of such resections performed before and after implementation. Results at all institutions were combined in a meta-analysis to estimate the overall change in the mean number of items documented. RESULTS: The operative notes for 325 transurethral bladder tumor resections during checklist use were compared to those for 428 performed before checklist implementation. Checklist use increased the mean number of items reported from 4.8 to 8.0 per resection, resulting in a mean increase of 3.3 items (95% CI 1.9-4.7) on meta-analysis. With the checklist the percentage of reports that included all 10 items increased from 0.5% to 27% (p <0.0001). Surgeons who reported more checklist items tended to have a slightly higher proportion of biopsies containing muscle, although not at conventional significance (p = 0.062). CONCLUSIONS: The use of a 10-item checklist during transurethral resection of bladder tumor improved the reporting of critical procedural elements. Although there was no clear impact on the inclusion of muscle in the specimen, checklist use may enhance surgeon attention to important aspects of the procedure and be a lever for quality improvement.