15 years of patient-reported outcomes in clinical trials leading to GU cancer drug approvals: a systematic review on the quality of data reporting and analysis.

Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies. Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022. ClinicalTrials.gov and PubMed were used to retrieve relevant data. PRO data was screened, and analytic tools, interpretation methods in the published papers and study protocols were reviewed. Compliance with PRO reporting standards were assessed using PRO Endpoint Analysis Score (PROEAS), a 24-point scoring scale from Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium (SISAQOL). Findings: We assessed 40 trial protocols with 27,011 participants, resulting in 14 renal cell cancer (RCC), 16 prostate cancer (PC), and 10 urothelial cancer (UC) approvals. PRO data was published for 27 trials, with 23 PRO publications (85%) focusing solely on PRO data, while 4 (15%) included PRO data in the original paper. Median time between primary clinical and secondary paper with PRO data was 10.5 months (range: 9-25 months). PROs were not planned as primary endpoints for any study but 14 (52%) reported them as secondary, 10 (37%) as exploratory outcomes, and 3 (11%) lacked any clarity on PRO data as endpoint. Mean PROEAS score of all GU cancers was 11.10 (range: 6-15), RCC (11.86, range: 6-15), UC (11.50, range: 9-14), and PC (10.56, range: 6-15). None met all the SISAQOL recommendations. Interpretation: Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint. These improvements are essential for facilitating interpretation and application of PRO study findings to define patient care. Funding: None.

Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. METHODS: We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. RESULTS: We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21-0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09-0.87, p = 0.0325). CONCLUSION: PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality worldwide. This is largely due to the lack of routine screening protocols, an absence of symptoms in early-stage disease leading to late detection, and a paucity of effective treatment options. Critically, the majority of patients either present with metastatic disease or rapidly develop metastatic disease. Thus, there is an urgent need to deepen our understanding of metastasis in PDAC. During metastasis, tumor cells escape from the primary tumor, enter the circulation, and travel to a distant site to form a secondary tumor. In order to accomplish this relatively rare event, tumor cells develop an enhanced ability to detach from the primary tumor, migrate into the surrounding matrix, and invade across the basement membrane. In addition, cancer cells interact with the various cell types and matrix proteins that comprise the tumor microenvironment, with some of these factors working to promote metastasis and others working to suppress it. In PDAC, many of these processes are not well understood. The purpose of this review is to highlight recent advances in the cell biology of the early steps of the metastatic cascade in pancreatic cancer. Specifically, we will examine the regulation of epithelial-to-mesenchymal transition (EMT) in PDAC and its requirement for metastasis, summarize our understanding of how PDAC cells invade and degrade the surrounding matrix, and discuss how migration and adhesion dynamics are regulated in PDAC to optimize cancer cell motility. In addition, the role of the tumor microenvironment in PDAC will also be discussed for each of these invasive processes.

Cost Effectiveness of Treatment Sequences in Advanced Renal Cell Carcinoma.

BACKGROUND: The treatment landscape for metastatic renal cell carcinoma (mRCC) has significantly evolved in recent years. Without direct comparator trials, factors such as cost effectiveness (CE) are important to guide decision-making. OBJECTIVE: To assess the CE of guideline-recommended approved first- and second-line treatment regimens. DESIGN, SETTING, AND PARTICIPANTS: A comprehensive Markov model was developed to analyze the CE of the five current National Comprehensive Cancer Network-recommended first-line therapies with appropriate second-line therapy for patient cohorts with International Metastatic RCC Database Consortium favorable and intermediate/poor risk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Life years, quality-adjusted life years (QALYs), and total accumulated costs were estimated using a willingness-to-pay threshold of $150 000 per QALY. One-way and probabilistic sensitivity analyses were performed. RESULTS AND LIMITATIONS: In patients with favorable risk, pembrolizumab + lenvatinib followed by cabozantinib added $32 935 in costs and yielded 0.28 QALYs, resulting in an incremental CE ratio (ICER) of $117 625 per QALY in comparison to pembrolizumab + axitinib followed by cabozantinib. In patients with intermediate/poor risk, nivolumab + ipilimumab followed by cabozantinib added $2252 in costs and yielded 0.60 QALYs compared to cabozantinib followed by nivolumab, yielding an ICER of $4184. Limitations include differences in median follow-up duration between treatments. CONCLUSIONS: Pembrolizumab + lenvatinib followed by cabozantinib, and pembrolizumab + axitinib followed by cabozantinib were cost-effective treatment sequences for patients with favorable-risk mRCC. Nivolumab +ipilimumab followed by cabozantinib was the most cost-effective treatment sequence for patients with intermediate-/poor-risk mRCC, dominating all preferred treatments. PATIENT SUMMARY: Because new treatments for kidney cancer have not been compared head to head, comparison of their cost and efficacy can help in making decisions about the best treatments to use first. Our model showed that patients with a favorable risk profile are most likely to benefit from pembrolizumab and lenvatinib or axitinib followed by cabozantinib, while patients with an intermediate or poor risk profile will probably benefit most from nivolumab and ipilimumab followed by cabozantinib.

Vitrification versus slow freezing of human ovarian tissue: a systematic review and meta-analysis of histological outcomes.

A systematic review and meta-analysis of pertinent literature published from 2006 to January 2022 were conducted to study and compare vitrification and slow freezing, the two prominent methods of ovarian tissue cryopreservation. The primary outcome measures for this study were (1) proportion of intact primordial follicles, (2) proportion of intact stromal cells, (3) proportion of DNA fragmentation in primordial follicles, and (4) mean primordial follicle density. This meta-analysis of 19 studies revealed a significantly greater proportion of intact stromal cells in vitrified tissue versus slow-frozen tissue. No significant differences upon pooled analyses were observed between the two cryopreservation methods with respect to the proportion of intact primordial follicles, proportion of DNA fragmentation, or mean primordial follicle density. Due to differences seen in stromal cell viability, vitrification may be a preferred option to preserve histology of tissue. However, more work should be done to compare the two freezing techniques with less heterogeneity caused by patients, samples, and protocols.

Penile cancer: Updates in systemic therapy.

Penile cancer is a rare genitourinary malignancy with a greater incidence in parts of Asia, South America, and Africa. Outcomes are very poor in patients with advanced disease and in those who do not respond to first-line multimodal therapy. Among systemic therapy options, platinum-based chemotherapy is used in the first-line; however, approximately half of patients do not benefit. Response rates to systemic therapy as subsequent line treatment are historically dismal. There is also a paucity of prognostic and predictive tools within the context of penile cancer. As such, there remains an urgent need to expand systemic treatment options for patients with advanced penile cancer. The purpose of this review is to summarize the existing evidence for standard-of-care lines of systemic treatment, examine the potential of novel lines of systemic therapy, and provide an update as to the status of these new therapies within the context of penile cancer.

Metastasis-directed Therapy Without Androgen Deprivation Therapy in Solitary Oligorecurrent Prostate Cancer.

PURPOSE: As controversy remains regarding the role of metastasis-directed therapy in patients with oligometastatic prostate cancer, we sought to characterize outcomes of metastasis-directed therapy without concomitant androgen deprivation therapy in the specific subset of patients with a solitary metastatic lesion on C-11 choline positron emission tomography imaging whose primary tumor has already been treated. MATERIALS AND METHODS: We identified 124 consecutive prostate cancer patients from 2008 to 2018 with a solitary oligorecurrent metastatic lesion on positron emission tomography imaging who were treated with metastasis-directed therapy without androgen deprivation therapy from the Mayo Clinic C-11 choline registry. Metastasis-directed therapy consisted of either stereotactic body radiation therapy or surgical excision. RESULTS: Of these 124 patients, 67 were treated with surgery (median follow-up 54 months) and 57 patients were treated with stereotactic body radiation therapy (median follow-up 53 months). Of patients treated with surgery, 80.5% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 29%. Median time to initiation of systemic therapy in this cohort was 18.5 months (interquartile range 8.4-44.7 months). Meanwhile, for patients treated with stereotactic body radiation therapy, 40.3% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 17%. Similarly, median time to initiation of systemic therapy was 17.8 months (interquartile range 7.1-42.3 months). CONCLUSIONS: This study represents the first reported series of metastasis-directed therapy without androgen deprivation therapy in patients with solitary oligorecurrent metastatic prostate cancer. These results suggest that metastasis-directed therapy without androgen deprivation therapy can delay initiation of systemic therapy and highlight the need for further prospective study for select patients with solitary metastatic recurrences of prostate cancer.

Immune-based therapies in penile cancer.

Penile cancer is a rare genitourinary malignancy that is associated with poor outcomes and severely limited therapeutic options that are generally non-curative when used to treat localized disease with high-risk features or advanced disease. To address the unmet need for treatment modalities with increased effectiveness, immune-based therapies such as immune-checkpoint blockade, human papilloma virus (HPV)-directed vaccines and adoptive T cell therapies have emerged as potential treatment options for advanced penile cancer. A diverse array of immune cells such as cytotoxic T lymphocytes (CTLs), tumour-associated macrophages and myeloid-derived suppressor cells have been shown to infiltrate penile cancer tumours, with distinct immune landscapes being demonstrated in HPV-positive compared with HPV-negative tumours. Study results have also demonstrated the prognostic value of immune cells such as tumour-associated macrophages, immune markers such as programmed death ligand-1, and HPV-status in penile cancer. Taken together, these findings underscore the clinical relevance of the tumour immune microenvironment as a source of both prognostic indicators and potential therapeutic targets for immune-based therapies. Current evidence regarding the safety and efficacy of immune-based therapies is limited in penile cancer, but a number of clinical and preclinical studies are ongoing to evaluate these therapies in this disease based on promising results from studies in other malignancies, including other squamous cell carcinomas. In addition, an opportunity exists to combine immune-based therapies with existing lines of systemic therapy to offer the most benefit to patients with advanced penile cancer. Future work should focus on expansion of preclinical models for immune-based drug discovery.

Calibration and standardization of extracellular vesicle measurements by flow cytometry for translational prostate cancer research.

Extracellular vesicles (EVs) are microscopic particles released naturally in biofluids by all cell types. Since EVs inherits genomic and proteomic patterns from the cell of origin, they are emerging as promising liquid biomarkers for human diseases. Flow cytometry is a popular method that is able to detect, characterize and determine the concentration of EVs with minimal sample preparation. However, the limited awareness of the scientific community to utilize standardization and calibration methods of flow cytometers is an important roadblock for data reproducibility and inter-laboratory comparison. A significant collaborative effort by the Extracellular Vesicle Flow Cytometry Working Group has led to the development of guidelines and best practices for using flow cytometry and reporting data in a way to improve rigor and reproducibility in EV research. At first look, standardization and calibration of flow cytometry for EV detection may seem burdensome and technically challenging for non-academic laboratories with limited technical training and knowledge in EV flow cytometry. In this study, we build on prior research efforts and provide a systematic approach to evaluate the performance of a high sensitivity flow cytometer (herein Apogee A60-Micro Plus) and fine-tune settings to improve detection sensitivity for EVs. We performed calibration of our flow cytometer to generate data with comparable units (nanometers, MESF). Finally, we applied our optimized protocol to measure the concentrations of prostate-derived EVs in healthy individuals and prostate cancer patients. In conclusion, our proof-of-feasibility study can serve as a scientific and technical framework for other groups motivated in using flow cytometry for EV research.

Establishment of a Pediatric Ovarian and Testicular Cryopreservation Program for Malignant and Non-Malignant Conditions: The Mayo Clinic Experience.

STUDY OBJECTIVES: To describe the structure of a pediatric fertility preservation (FP) program and to share safety and patient satisfaction data. DESIGN: The FP program operates under prospective research protocols approved by the Mayo Clinic Institutional Review Board (IRB). SETTING: The FP program is a multidisciplinary effort between pediatric gynecology, reproductive endocrinology, pediatric urology, pediatric surgery, and laboratory medicine. PARTICIPANTS: The FP program enrolls patients between 0-17 years of age who have been diagnosed with a fertility-threatening condition and/or are scheduled to undergo gonadotoxic treatment. INTERVENTIONS: FP is offered in the form of ovarian tissue cryopreservation (OTC) and testicular (TTC) tissue cryopreservation. MAIN OUTCOME MEASURES: The outcome measures are the safety of the procedure and results of patient surveys conducted by phone using a standard list of questions to assess attitudes towards FP. RESULTS: To date, we have enrolled 38 OTC and 37 TTC patients. The median age (range) of OTC and TTC patients was 11 years (0.83-17 years) and 10 years (0.92-17 years) at the time of enrollment, respectively. Childhood cancers currently represent 88% of the fertility-threatening diagnoses. Meanwhile, patients with non-malignant conditions include those with gender dysphoria, aplastic anemia, and Turner's syndrome. To date, no serious adverse events (SAEs) have been reported following surgery. According to n = 34 one-year follow-ups, 100% of parents felt that FP was a good decision. CONCLUSION: Consistent with the literature, our data suggests FP is safe and improves the quality of care provided to pediatric patients for their fertility-threatening diagnoses and/or treatments. TRIAL REGISTRATION: NCT02872532, NCT02646384.

Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver Model.

PURPOSE: The purpose of this study was to establish the feasibility of performing a urinary bladder vascularized composite allograft transplantation for either bladder augmentation or neobladder creation. MATERIALS AND METHODS: Six adult cadavers were studied. Cadavers were excluded for any previous pelvic surgery, radiation, vascular surgery or history of pelvic malignancy. An intravascular colored silicone and barium mixture was injected and both computerized tomography scans and gross dissections were performed. Contrast enhanced computerized tomography imaging was used to delineate urinary bladder vascular anatomy variability. Bladders were explanted en bloc from 2 cadavers with bilateral vascular pedicles based on the external iliac vessels and "transplanted" to replicate a bladder transplant. RESULTS: Contrast enhanced 3-D-computerized tomography reconstructions and cadaver dissections revealed distal vascular variability with proximal blood supply based primarily on the internal iliac artery. Urinary bladder vascularized composite allograft transplantation was successfully performed during 2 mock transplants with the vascular anastomosis done to the recipient external iliac artery and vein. CONCLUSIONS: Urinary bladder vascularized composite allograft transplantation is technically and anatomically feasible. This procedure may obviate the use of intestinal segments for bladder reconstruction in select patients. A phase 1 clinical trial is in progress.

Radium-223 in the Third-Line Setting in Metastatic Castration-Resistant Prostate Cancer: Impact of Concomitant Use of Enzalutamide on Overall Survival (OS) and Predictors of Improved OS.

INTRODUCTION: Radium-223 (Ra-223) has been recommended for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). Second-generation hormone therapy in combination with Ra-223 in mCRPC has been utilized, yet its benefit has not been well elucidated. We investigated the potential survival benefit of concomitant enzalutamide with Ra-223 in the third-line setting and predictors of improved overall survival (OS). PATIENTS AND METHODS: We retrospectively identified 51 patients with bone-dominant mCRPC that were treated with Ra-223 in the postchemotherapy and post-hormone therapy setting, either alone (group A; n = 32) or with concomitant enzalutamide (group B; n = 19). The primary endpoint was to study the OS difference between groups A and B. The secondary endpoint was to identify predictors of improved OS with Ra-223 in the third-line setting. RESULTS: Mean age was 70.9 years, median baseline prostatic-specific antigen (PSA) was 23.1 ng/mL, alkaline phosphatase was 91 IU/L, and hemoglobin was 12.5 g/dL. There was no difference in median OS between groups A and B, at 20.4 versus 17.5 months, respectively (P = .5186). In univariate and multivariate analyses, only pre-Ra-223 PSA < 30 ng/mL and Eastern Cooperative Oncology Group performance status < 2 were associated with improved OS. CONCLUSION: In our study cohort, concomitant use of enzalutamide with Ra-223 in the mCRPC setting was not associated with improved OS. Only pretreatment PSA < 30 ng/mL and pretreatment Eastern Cooperative Oncology Group performance status < 2 were associated with improved OS. Further prospective studies are warranted.

Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

A Survey of Urology Residency Program Directors Assessing Criteria to Interview Applicants during the COVID-19 Pandemic.

INTRODUCTION: We aimed to determine criteria of interest to urology residency program directors when selecting applicants for residency interviews during the COVID-19 pandemic. METHODS: An anonymous survey was sent via email to all urology residency program directors across the United States. Program directors were asked to assign the degree of importance (1-5, with 5 being very important) of selected factors in deciding which applicants to interview. Surveys were distributed and study data were managed using REDCap. Descriptive statistical analyses were performed. RESULTS: In total, 130 urology residency program directors were contacted and 64 (49.3%) responded to the survey. Urology letter(s) of recommendation based on nonvirtual rotation(s), urology clerkship grades, research experience, and visa status of the applicant were cited as the most important factors in selecting applicants for interview with median importance ratings of 5, 4, 4, and 5, respectively. Urology letter(s) of recommendation based on virtual rotation(s), virtual sub-internship(s), and participation in social media activities were the least important in selecting applicants for interviews with median importance ratings of 2 for each. Notably, urology letter(s) of recommendation based on nonvirtual rotation(s) and visa status were consistently ranked as the most important factors by more than 50% of program directors. CONCLUSIONS: Urology program directors value urology letter(s) of recommendation from nonvirtual rotation(s), urology clerkship grades, research experience, and applicant visa status as the most important factors in selecting applicants for interviews during the COVID-19 pandemic. Virtual rotation(s) and social media activity were ranked the lowest among criteria that influence the selection process for interviews.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

BACKGROUND: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. METHODS: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. RESULTS: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Implementation of multiparametric magnetic resonance imaging technology for evaluation of patients with suspicion for prostate cancer in the clinical practice setting.

OBJECTIVES: To investigate the impact of implementing magnetic resonance imaging (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa) detection rates in men presenting with clinical suspicion for PCa in the clinical practice setting. PATIENTS AND METHODS: We performed a review of 1 808 consecutive men referred for elevated prostate-specific antigen (PSA) level between 2011 and 2014. The study population was divided into two groups based on whether MRI was used as a risk stratification tool. Univariable and multivariable analyses of biopsy rates and overall and clinically significant PCa detection rates between groups were performed. RESULTS: The MRI and PSA-only groups consisted of 1 020 and 788 patients, respectively. A total of 465 patients (45.6%) in the MRI group and 442 (56.1%) in the PSA-only group underwent biopsy, corresponding to an 18.7% decrease in the proportion of patients receiving biopsy in the MRI group (P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was significantly higher in the MRI vs the PSA-only group. In logistic regression analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.29-2.35; P < 0.001) and clinically significant PCa detection (OR 2.04, 95% CI 1.48-2.80; P < 0.001) were higher in the MRI than in the PSA-only group after adjusting for clinically relevant PCa variables. CONCLUSION: Among men presenting with clinical suspicion for PCa, addition of MRI increases detection of clinically significant cancers while reducing prostate biopsy rates when implemented in a clinical practice setting.

The Temporal Association of Robotic Surgical Diffusion with Overtreatment of the Small Renal Mass.

PURPOSE: We evaluated contemporary practice patterns in the management of small renal masses. MATERIALS AND METHODS: We identified 52,804 patients in the NCDB (National Cancer Database) who were diagnosed with a small renal mass (4 cm or less) between 2010 and 2014. Utilization trends of active surveillance, ablation and robotic, laparoscopic and open surgical techniques were compared among all comers, elderly patients 75 years old or older and individuals with competing health risks, defined as a Charlson index of 2 or greater. Multivariable logistic regression models were used to assess factors associated with robotic renal surgery and active surveillance. RESULTS: Surgery remained the primary treatment modality across all years studied, performed in 75.0% and 74.2% of cases in 2010 and 2014, respectively. Although increases in active surveillance from 4.8% in 2010 to 6.0% in 2014 (p <0.001) and robotic renal surgery (22.1% in 2010 to 39.7% in 2014, p <0.001) were observed, the increase in the proportion of small renal masses treated with robotic partial and radical nephrectomy was greater than that of active surveillance (82.0% and 63.0%, respectively, vs 25.0%). Subgroup analyses in individuals 75 years old or older, or with a Charlson index of 2 or greater likewise revealed preferential increases in robotic surgery vs active surveillance. On multivariable analysis later year of diagnosis was associated with increased performance of robotic renal surgery compared to active surveillance (2014 vs 2010 OR 1.44, 95% CI 1.20-1.72, p <0.001) and nonrobotic procedural interventions (2014 vs 2010 OR 2.59, 95% CI 2.30-2.93, p <0.001). CONCLUSIONS: Robotic surgical extirpation has outpaced the adoption of active surveillance of small renal masses. This raises concern that the diffusion of robotic technology propagates overtreatment, particularly among elderly and comorbid individuals.