Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Results from a Canadian consensus forum of key controversial areas in the management of advanced prostate cancer: Recommendations for Canadian healthcare providers.

INTRODUCTION: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) has created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment. METHODS: A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions, and analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥75% for "consensus agreement," >50% for "near-consensus," and ≤50% for "no consensus." RESULTS: The panel was comprised of 29 PCa experts, including urologists (n=12), medical oncologists (n=12), and radiation oncologists (n=5). Voting took place for 65 predetermined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas, including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling. CONCLUSIONS: The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.

Treatment and Patient Selection for Patients with Metastatic Castration-resistant Prostate After Progression on Docetaxel and Abiraterone/Enzalutamide: When to Play Your CARD and When to Do Your PARP.

For patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after an androgen receptor axis-targeted therapy and docetaxel, poly (ADP-ribose) polymerase (PARP) inhibitors and chemotherapy with cabazitaxel have shown promise. We address the trials for the two approaches and consider possible sequencing of these drugs. We suggest that only patients with a BRCA2 mutation should receive a PARP inhibitor, and docetaxel or cabazitaxel should be favored in the absence of BRCA2 alterations, provided the patient is naïve to these drugs.

Psychological morbidity associated with prostate cancer: Rates and predictors of depression in the RADICAL PC study.

INTRODUCTION: Across all cancer sites and stages, prostate cancer has one of the greatest median five-year survival rates, highlighting the important focus on survivorship issues following diagnosis and treatment. In the current study, we sought to evaluate the prevalence and predictors of depression in a large, multicenter, contemporary, prospectively collected sample of men with prostate cancer. METHODS: Data from the current study were drawn from the baseline visit of men enrolled in the RADICAL PC study. Men with a new diagnosis of prostate cancer or patients initiating androgen deprivation therapy for prostate cancer for the first time were recruited. Depressive symptoms were evaluated using the nine-item version of the Patient Health Questionnaire (PHQ-9). To evaluate factors associated with depression, a multivariable logistic regression model was constructed, including biological, psychological, and social predictor variables. RESULTS: Data from 2445 patients were analyzed. Of these, 201 (8.2%) endorsed clinically significant depression. Younger age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.16-1.60 per 10-year decrease), being a current smoker (OR 2.77, 95% CI 1.66-4.58), former alcohol use (OR 2.63, 95% CI 1.33-5.20), poorer performance status (OR 5.01, 95% CI 3.49-7.20), having a pre-existing clinical diagnosis of depression or anxiety (OR 3.64, 95% CI 2.42-5.48), and having high-risk prostate cancer (OR 1.49, 95% CI 1.05-2.12) all conferred independent risk for depression. CONCLUSIONS: Clinically significant depression is common in men with prostate cancer. Depression risk is associated with a host of biopsychosocial variables. Clinicians should be vigilant to screen for depression in those patients with poor social determinants of health, concomitant disability, and advanced disease.

Androgen Deprivation Therapy and Mental Health: Impact on Depression and Cognition.

Androgen deprivation therapy (ADT) is a common treatment for many men with prostate cancer. Use of ADT can have significant impacts on the mental health of patients with both localized and advanced disease. Prostate cancer patients receiving ADT have a 41% higher risk of depression and a 47% higher risk of dementia. Risk factors for the development of depression in this group of men include older age, marital status, greater comorbidity, and a previous history of depression, while being retired may offer a protective effect. Optimal treatment strategies for depression for these men are not well established in the literature. PATIENT SUMMARY: We reviewed the association between androgen deprivation therapy (ADT) use by men with prostate cancer and the risk of mental health issues. There appears to be a higher risk of both depression and cognitive impairment for men receiving ADT. Optimal treatments for depression for men on ADT are still not well studied.

Controversial issues in the management of patients with advanced prostate cancer: Results from a Canadian consensus forum.

INTRODUCTION: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. METHODS: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). RESULTS: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. CONCLUSIONS: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

Depression and prostate cancer: A focused review for the clinician.

Prostate cancer is the most common malignancy among men. Given its prevalence and relatively low mortality rates, several biopsychosocial survivorship issues have garnered recent attention. This article reviews the literature on the association between depression and prostate cancer, emphasizing key practice points relevant for clinicians. Depression is prevalent among men with prostate cancer, with approximately 1 in 6 patients experiencing clinical depression. Suicidal ideation is also not uncommon in this population and does not always present in those with other depressive symptoms. While choice of definitive cancer treatment (radiation or surgery) does not seem to affect depressive symptoms, receipt of androgen deprivation therapy appears to have a negative effect. Not only are patients at increased risk for depression following a prostate cancer diagnosis, but depression itself seems to adversely affect oncologic outcomes. We were not able to identify any clinical trials examining the efficacy of antidepressant medications for depressive symptoms in these patients, however population-based studies suggest antidepressant prescriptions are commonly utilized. Taken together, the literature on the intersection between urologic oncology and psychology/psychiatry affirms the importance of depression among men with prostate cancer. Clinicians should consider assessment of this symptom domain and treat or refer judiciously. Clinical trials represent a priority for future research.

Temporal trends in management and outcomes of testicular cancer: A population-based study.

BACKGROUND: Treatment guidelines for early-stage testicular cancer have increasingly recommended de-escalation of therapy with surveillance strategies. This study was designed to describe temporal trends in routine clinical practice and to determine whether de-escalation of therapy is associated with inferior survival in the general population. METHODS: The Ontario Cancer Registry was linked to electronic records of treatment to identify all patients diagnosed with testicular cancer treated with orchiectomy in Ontario during 2000-2010. Treatment after orchiectomy was classified as radiotherapy (RT), retroperitoneal lymph node dissection (RPLND), chemotherapy, or none. Surveillance was defined as no identified treatment within 90 days of orchiectomy. Overall survival (OS) and cancer-specific survival (CSS) were measured from the date of orchiectomy. RESULTS: The study population included 1564 and 1086 cases of seminomas and nonseminoma germ cell tumors (NSGCTs), respectively. Among patients with seminomas, there was a significant increase in the proportion of patients with no treatment within 90 days of orchiectomy (from 56% to 84%; P < .001); the use of RT decreased over time (from 38% to 8%; P < .001); and the use of chemotherapy remained stable (from 6% to 9%; P = .289). Practice patterns 90 days after orchiectomy remained stable over time among patients with NSGCTs: from 51% to 57% for no treatment (P = .435), from 43% to 43% for chemotherapy (P = .336), and from 9% to 3% for RPLND (P = .476). The OS rates for the entire cohort at 5 and 10 years were 97% and 96%, respectively; the CSS rates were 98% and 98%, respectively. There was no significant change in OS or CSS for patients with seminomas or NSGCTs during the study period. CONCLUSIONS: There has been substantial de-escalation in the treatment of testicular cancer in routine practice since 2000. Long-term survival in routine practice is excellent and has not decreased with the uptake of surveillance strategies. Cancer 2018;124:2724-2732. © 2018 American Cancer Society.

Partial cystectomy for urothelial carcinoma of the bladder: Practice patterns and outcomes in the general population.

INTRODUCTION: Partial cystectomy (PC) for urothelial carcinoma (UC) in selected patients may avoid the morbidity of radical cystectomy (RC). We describe use and outcomes of PC for UC in routine clinical practice. METHODS: All patients with urothelial carcinoma of the bladder (UCB) undergoing PC or RC in Ontario from 1994-2008 were identified using the Ontario Cancer Registry and linked electronic records. Pathology reports were reviewed. Variables associated with PC use were identified using logistic regression. Cox proportional hazards model identified factors affecting cancer-specific (CSS) and overall survival (OS). RESULTS: A total of 3320 patients underwent PC (n=181; 5%) or RC (n=3139; 95%) from 1994-2008. PC patients were older (36% 80+ years vs. 19%; p<0.001) and more likely to have organ-confined (

An analysis of the readability of patient information materials for common urological conditions.

INTRODUCTION: Health literacy has been shown to be an important determinant of outcomes in numerous disease states. In an effort to improve health literacy, the Canadian Urological Association (CUA) publishes freely accessible patient information materials (PIMs) on common urological conditions. We sought to evaluate the readability of the CUA's PIMs. METHODS: All PIMs were accessed through the CUA website. The Flesch Reading Ease Score (FRES), the Flesch-Kincaid Grade Level (FKGL), and the number of educational graphics were determined for each PIM. Low FRES scores and high FKGL scores are associated with more difficult-to-read text. Average readability values were calculated for each PIM category based on the CUA-defined subject categorizes. The five pamphlets with the highest FKGL scores were revised using word substitutions for complex multisyllabic words and reanalyzed. The Kruskal-Wallis test was used to identify readability differences between PIM categories and paired t-tests were used to test differences between FKGL scores before and after revisions. RESULTS: Across all PIMs, FRES values were low (mean 47.5, standard deviation [SD] 7.47). This corresponded to an average FKGL of 10.5 (range 8.1-12.0). Among PIM categories, the infertility and sexual function PIMs exhibited the highest average FKGL (mean 11.6), however, differences in scores between categories were not statistically significant (p=0.38). The average number of words per sentence was also highest in the infertility and sexual function PIMs and significantly higher than other categories (mean 17.2; p=0.01). On average, there were 1.4 graphics displayed per PIM (range 0-4), which did not vary significantly by disease state (p=0.928). Simple words substitutions improved the readability of the five most difficult-to-read PIMs by an average of 3.1 grade points (p<0.01). CONCLUSIONS: Current patient information materials published by the CUA compare favourably to those produced by other organizations, but may be difficult to read for low-literacy patients. Readability levels must be balanced against the required informational needs of patients, which may be intrinsically complex.

Root Causes and Modifiability of 30-Day Hospital Readmissions after Radical Cystectomy for Bladder Cancer.

PURPOSE: Radical cystectomy is associated with high complication and rehospitalization rates. An understanding of the root causes of hospital readmissions and the modifiability of factors contributing to readmissions may decrease the morbidity associated with radical cystectomy. We characterize the indications for rehospitalization following radical cystectomy, and determine whether these indications represent immutable patient disease and procedure factors or whether they are modifiable. MATERIALS AND METHODS: From MarketScan® databases we identified patients younger than 65 years with a diagnosis of bladder cancer who underwent radical cystectomy between 2008 and 2011 and were readmitted to the hospital within 30 days of radical cystectomy. All associated ICD-9 codes in the index admission, subsequent outpatient claims and readmission claims were independently reviewed by 3 surgeons to determine a root cause of rehospitalization. Causes were broadly categorized as medical, surgical or infectious, and reviewers determined whether the readmission was modifiable. Multivariate logistical regression models were used to identify factors associated with rehospitalization. RESULTS: A total of 1,163 patients were included in the study and 242 (21%) were readmitted to the hospital within 30 days. Of these readmissions 26% were considered modifiable (kappa=0.71). Of the nonmodifiable readmissions an infectious cause accounted for 52% and a medical cause accounted for 48%, whereas of the modifiable readmissions 62% were due to surgical causes, 30% to medical and 8% to infectious causes. On multivariate analysis only discharge to a skilled nursing facility was associated with modifiable (OR 6.12, 95% CI 2.32-16.14) or nonmodifiable (OR 3.27, 95% CI 1.63-6.53) hospital readmissions. CONCLUSIONS: The majority of rehospitalizations after radical cystectomy are attributable its inherent morbidity. However, optimization of aspects of peri-cystectomy care could minimize the morbidity of radical cystectomy.

Design and feasibility of integrating personalized PRO dashboards into prostate cancer care.

OBJECTIVE: Patient-reported outcomes (PROs) are a valued source of health information, but prior work focuses largely on data capture without guidance on visual displays that promote effective PRO use in patient-centered care. We engaged patients, providers, and design experts in human-centered design of "PRO dashboards" that illustrate trends in health-related quality of life (HRQOL) reported by patients following prostate cancer treatment. MATERIALS AND METHODS: We designed and assessed the feasibility of integrating dashboards into care in 3 steps: (1) capture PRO needs of patients and providers through focus groups and interviews; (2) iteratively build and refine a prototype dashboard; and (3) pilot test dashboards with patients and their provider during follow-up care. RESULTS: Focus groups (n = 60 patients) prioritized needs for dashboards that compared longitudinal trends in patients' HRQOL with "men like me." Of the candidate dashboard designs, 50 patients and 50 providers rated pictographs less helpful than bar charts, line graphs, or tables (P < .001) and preferred bar charts and line graphs most. Given these needs and the design recommendations from our Patient Advisory Board (n = 7) and design experts (n = 7), we built and refined a prototype that charts patients' HRQOL compared with age- and treatment-matched patients in personalized dashboards. Pilot testing dashboard use (n = 12 patients) improved compliance with quality indicators for prostate cancer care (P < .01). CONCLUSION: PRO dashboards are a promising approach for integrating patient-generated data into prostate cancer care. Informed by human-centered design principles, this work establishes guidance on dashboard content, tailoring, and clinical use that patients and providers find meaningful.