Daniel A. Barocas

Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years

Importance Understanding the adverse effects of contemporary approaches to localized prostate cancer treatment could inform shared decision making. Objective To compare functional outcomes and adverse effects associated with radical prostatectomy, external beam radiation therapy (EBRT), and active surveillance. Design, Setting, and Participants Prospective, population-based, cohort study involving 2550 men (⩽80 years) diagnosed in 2011-2012 with clinical stage cT1-2, localized prostate cancer, with prostate-specific antigen levels less than 50 ng/mL, and enrolled within 6 months of diagnosis. Exposures Treatment with radical prostatectomy, EBRT, or active surveillance was ascertained within 1 year of diagnosis. Main Outcomes and Measures Patient-reported function on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Higher domain scores (range, 0-100) indicate better function. Minimum clinically important difference was defined as 10 to 12 points for sexual function, 6 for urinary incontinence, 5 for urinary irritative symptoms, 5 for bowel function, and 4 for hormonal function. Results The cohort included 2550 men (mean age, 63.8 years; 74% white, 55% had intermediate- or high-risk disease), of whom 1523 (59.7%) underwent radical prostatectomy, 598 (23.5%) EBRT, and 429 (16.8%) active surveillance. Men in the EBRT group were older (mean age, 68.1 years vs 61.5 years, Pu2009<u2009.001) and had worse baseline sexual function (mean score, 52.3 vs 65.2, Pu2009<u2009.001) than men in the radical prostatectomy group. At 3 years, the adjusted mean sexual domain score for radical prostatectomy decreased more than for EBRT (mean difference, −11.9 points; 95% CI, −15.1 to −8.7). The decline in sexual domain scores between EBRT and active surveillance was not clinically significant (−4.3 points; 95% CI, −9.2 to 0.7). Radical prostatectomy was associated with worse urinary incontinence than EBRT (−18.0 points; 95% CI, −20.5 to −15.4) and active surveillance (−12.7 points; 95% CI, −16.0 to −9.3) but was associated with better urinary irritative symptoms than active surveillance (5.2 points; 95% CI, 3.2 to 7.2). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in health-related quality of life or disease-specific survival (3 deaths) were noted (99.7%-100%). Conclusions and Relevance In this cohort of men with localized prostate cancer, radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence than either EBRT or active surveillance after 3 years and was associated with fewer urinary irritative symptoms than active surveillance; however, no meaningful differences existed in either bowel or hormonal function beyond 12 months or in in other domains of health-related quality-of-life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

Recent Changes in Prostate Cancer Screening Practices and Epidemiology

Purpose: Prostate specific antigen based screening for prostate cancer has had a significant impact on the epidemiology of the disease. Its use has been associated with a significant decrease in prostate cancer mortality but has also resulted in the over diagnosis and overtreatment of indolent prostate cancer, exposing many men to the harms of treatment without benefit. The USPSTF (U.S. Preventive Services Task Force) in 2008 issued a recommendation against screening men older than 75 years, and in 2012 against routine screening for all men, indicating that in its interpretation the harms of screening outweigh the benefits. We review changes in the use of prostate specific antigen testing, performance of prostate biopsy, incidence of prostate cancer and stage of disease at presentation since 2012. Materials and Methods: An English language literature search was performed for terms that included “prostate specific antigen,” “screening” and “United States Preventive Services Task Force” in various combinations. A total of 26 original studies had been published on the effects of the USPSTF recommendations on prostate specific antigen based screening or prostate cancer incidence in the United States as of December 1, 2016. Results: Review of the literature from 2012 through the end of 2016 indicates that there has been a decrease in prostate specific antigen testing and prostate biopsy. As a result, there has been a decline in the incidence of localized prostate cancer, including low, intermediate and high risk disease. The data regarding stage at presentation have yet to mature but there are some early signs of a shift toward higher burden of disease at presentation. Conclusions: These findings raise concern about a reversal of the observed improvement in prostate cancer specific mortality during preceding decades. Alternative screening strategies would 1) incorporate patient preferences by allowing shared decision‐making, 2) preserve the survival benefits associated with screening, 3) improve the specificity of screening to reduce unnecessary biopsies and detection of low risk disease, and 4) promote the use of active surveillance for low risk cancers if they are detected.

Magnetic resonance-ultrasound fusion prostate biopsy in the diagnosis of prostate cancer

The advent of multiparametric magnetic resonance imaging (MRI) has ushered in a new era for urologists who perform prostate needle biopsies. The fusion of MRI with transrectal ultrasound (US) allows the direct targeting of suspicious lesions, which has been shown to improve the performance of conventional random biopsy techniques by increasing detection of clinically relevant disease while also decreasing detection of low-risk cancer. However, as with any new technology, many questions regarding effectiveness, reproducibility, and generalizability still remain. In this review, we (1) provide a summary of the various sequences that comprise a MRI of the prostate; (2) evaluate the 3 different ways of incorporating MRI into targeted biopsies of the prostate including in-bore MRI-guided biopsy, cognitive fusion, and device-mediated fusion; (3) review the sensitivity of MR-US fusion in the detection of clinically significant and clinically insignificant disease; and (4) review the barriers to the widespread implementation of MR-US fusion into everyday practice. Whereas other articles in this issue of Urologic Oncology Seminars will discuss other aspects of MRI in the management of prostate cancer, the purpose of this article is to provide an overview of MR-US fusion biopsies in the diagnosis of prostate cancer.

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial

BACKGROUNDnRadical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy.nnnMETHODSnThe RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676.nnnFINDINGSnBetween July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group).nnnINTERPRETATIONnIn patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types.nnnFUNDINGnNational Institutes of Health National Cancer Institute.

Oncologic Outcomes after Anterior Exenteration for Muscle Invasive Bladder Cancer in Women

PURPOSEnWe investigated oncologic and urinary outcomes after anterior exenteration for urothelial cell carcinoma in females, identifying tumor characteristics associated with female pelvic organ involvement. We hypothesized that a lack of trigonal or bladder floor tumor, intraoperative palpable posterior mass and clinical lymphadenopathy is associated with a lack of female pelvic organ involvement.nnnMATERIALS AND METHODSnWe retrospectively reviewed the charts of female patients who underwent radical cystectomy at our institution from 1999 to 2014. Patient and operative characteristics were extracted from the electronic medical record, and performance of hysterectomy was tested for association with disease recurrence. Categorical and continuous variables were analyzed with the chi-square and Student t-test, and Kaplan-Meier analysis was performed to determine recurrence-free survival according to hysterectomy performance. Women who had neobladder creation were additionally evaluated for an association between hysterectomy status, and nighttime wetting and catheter use.nnnRESULTSnOf 322 eligible patients 160 with urothelial cancer did not have a hysterectomy before cystectomy. Mean followup was 2.2 years (SD 2.8). There were 22 patients (13.8%) who had recurrence during followup. No patient or surgical factor other than use of adjuvant chemotherapy or radiation (p <0.01) was associated with recurrence. Of 139 women 32 (23.0%) who underwent exenteration had female pelvic organ involvement. At least 1 of the 3 characteristics of interest were present in 28 of 99 (28.3%) women with any genitourinary organ involvement compared to only 4 of 40 (10.0%) of those who did not (p=0.01). Nighttime continence ranged between 21.9% and 48% but there was no significant association with continence and hysterectomy status.nnnCONCLUSIONSnLack of trigonal/bladder floor tumor, palpable posterior mass and clinical lymphadenopathy is associated with the absence of pelvic organ involvement. Individualized risk assessment using these factors along with patient preferences should be used to guide surgical planning.

Doing More for More: Unintended Consequences of Financial Incentives for Oncology Specialty Care

BACKGROUNDnSpecialty care remains a significant contributor to health care spending but largely unaddressed in novel payment models aimed at promoting value-based delivery. Bladder cancer, chiefly managed by subspecialists, is among the most costly. In 2005, Centers for Medicare and Medicaid Services (CMS) dramatically increased physician payment for office-based interventions for bladder cancer to shift care from higher cost facilities, but the impact is unknown. This study evaluated the effect of financial incentives on patterns of fee-for-service (FFS) bladder cancer care.nnnMETHODSnData from a 5% sample of Medicare beneficiaries from 2001-2013 were evaluated using interrupted time-series analysis with segmented regression. Primary outcomes were the effects of CMS fee modifications on utilization and site of service for procedures associated with the diagnosis and treatment of bladder cancer. Rates of related bladder cancer procedures that were not affected by the fee change were concurrent controls. Finally, the effect of payment changes on both diagnostic yield and need for redundant procedures were studied. All statistical tests were two-sided.nnnRESULTSnUtilization of clinic-based procedures increased by 644% (95% confidence interval [CI] = 584% to 704%) after the fee change, but without reciprocal decline in facility-based procedures. Procedures unaffected by the fee incentive remained unchanged throughout the study period. Diagnostic yield decreased by 17.0% (95% CI = 12.7% to 21.3%), and use of redundant office-based procedures increased by 76.0% (95% CI = 59% to 93%).nnnCONCLUSIONSnFinancial incentives in bladder cancer care have unintended and costly consequences in the current FFS environment. The observed price sensitivity is likely to remain a major issue in novel payment models failing to incorporate procedure-based specialty physicians.

Impact of Adherence to Quality Measures for Localized Prostate Cancer on Patient-reported Health-related Quality of Life Outcomes, Patient Satisfaction, and Treatment-related Complications.

Background and Objective:Quality measures used in pay-for-performance systems are intended to address specific quality goals, such as safety, efficiency, effectiveness, timeliness, equity, and patient-centeredness. Given the small number of narrowly focused measures in prostate cancer care, we sought to determine whether adherence to any of the available payer-driven quality measures influences patient-centered outcomes, including health-related quality of life (HRQOL), patient satisfaction, and treatment-related complications. Methods:The Comparative Effectiveness Analysis of Surgery and Radiation study is a population-based, prospective cohort study that enrolled 3708 men with clinically localized prostate cancer during 2011 and 2012, of whom 2601 completed the 1-year survey and underwent complete chart abstraction. Compliance with 6 quality indicators endorsed by national consortia was assessed. Multivariable regression was used to determine the relationship between indicator compliance and Expanded Prostate Cancer Index Composite (EPIC-26) instrument summary scores, satisfaction scale scores (service satisfaction scale for cancer care), and treatment-related complications. Results:Overall rates of compliance with these quality measures ranged between 64% and 88%. Three of the 6 measures were weakly associated with 1-year sexual function and bowel function scores (&bgr;=−4.6, 1.69, and 2.93, respectively; P⩽0.05), whereas the remaining measures had no significant relationship with patient-reported HRQOL outcomes. Satisfaction scores and treatment-related complications were not associated with quality measure compliance. Conclusions:Compliance with available nationally endorsed quality indicators, which were designed to incentivize effective and efficient care, was not associated with clinically important changes in patient-centered outcomes (HRQOL, satisfaction, or complications) within 1-year.

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

PURPOSEnPrevious 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.nnnMATERIALS AND METHODSnWe 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.nnnRESULTSnThe 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 (pxa0=xa00.062).nnnCONCLUSIONSnThe 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.

Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy

Purpose: Level I evidence supports the usefulness of neoadjuvant cisplatin based chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced traditional MVAC, we compared pathological response and survival rates in patients with locally advanced bladder cancer who received neoadjuvant chemotherapy with dose dense MVAC vs gemcitabine and cisplatin. Materials and Methods: We retrospectively reviewed the records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent cystectomy at a total of 20 contributing institutions from 2000 to 2015. Patients with cT3‐4aN0M0 disease were selected for this analysis. The rates of ypT0N0 and ypT1N0 or less were compared between the gemcitabine and cisplatin, and dose dense MVAC regimens. Two multivariable Cox proportional hazards regression models of overall mortality were generated using preoperative and postoperative data. Results: Of the patients who underwent neoadjuvant chemotherapy and radical cystectomy during the study period 319 met our inclusion criteria. A significantly lower rate of ypT0N0 was observed in the gemcitabine and cisplatin arm than in the dose dense MVAC arm (14.6% vs 28.0%, p = 0.005). The rate of ypT1N0 or less was 30.1% for gemcitabine and cisplatin compared to 41.0% for dose dense MVAC (p = 0.07). The mean Kaplan‐Meier estimates of overall survival in the gemcitabine and cisplatin, and dose dense MVAC groups were 4.2 and 7.0 years, respectively (p = 0.001). On multivariable cox regression analysis based on preoperative data patients who received gemcitabine and cisplatin were at higher risk for death than patients who received dose dense MVAC (HR 2.07, 95% CI 1.25–3.42, p = 0.003). Lymph node invasion (HR 1.97, 95% CI 1.15–3.36, p = 0.01) and hydronephrosis (HR 2.18, 95% CI 1.43–3.30, p <0.001) were also associated with higher risk of death. Conclusions: In our retrospective cohort of patients with locally advanced bladder cancer dose dense MVAC was associated with higher complete pathological response and improved survival rates compared to gemcitabine and cisplatin. A clinical trial is warranted to validate these hypothesis generating results to test the superiority of neoadjuvant dose dense MVAC in patients with locally advanced bladder cancer.

The Influence of Psychosocial Constructs on the Adherence to Active Surveillance for Localized Prostate Cancer in a Prospective, Population-based Cohort

OBJECTIVEnTo evaluate the influence of psychosocial factors such as prostate cancer (PCa) anxiety, social support, participation in medical decision-making (PDM), and educational level on patient decisions to discontinue PCa active surveillance (AS) in the absence of disease progression.nnnMETHODSnThe Comparative Effectiveness Analysis of Surgery and Radiation study is a prospective, population-based cohort study of men with localized PCa diagnosed in 2011-2012. PCa anxiety, social support, PDM, educational level, and patient reasons for discontinuing AS were assessed through patient surveys. A Cox proportional hazards model examined the relationship between psychosocial variables and time to discontinuation of AS.nnnRESULTSnOf 531 patients on AS, 165 (30.9%) underwent treatment after median follow-up of 37 months. Whereas 69% of patients cited only medical reasons for discontinuing AS, 31% cited at least 1 personal reason, and 8% cited personal reasons only. Patients with some college education discontinued AS significantly earlier (hazard ratio: 2.0, 95% confidence interval: 1.2, 3.2) than patients with less education. PCa anxiety, social support, and PDM were not associated with seeking treatment.nnnCONCLUSIONnWe found that 31% of men who choose AS for PCa discontinue AS within 3 years. Eight percent of men who sought treatment did so in the absence of disease progression. Education, but not psychosocial factors, seems to influence definitive treatment-seeking. Future research is needed to understand how factors unrelated to disease severity influence treatment decisions among patients on AS to identify opportunities to improve adherence to AS.