Decisional Conflict Among Patients Newly Diagnosed With Clinical T1 Renal Masses: A Prospective Study.

PURPOSE: Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer. MATERIALS AND METHODS: From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient. RESULTS: Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94). CONCLUSIONS: In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.

Near Complete Response to Platinum-based Systemic Chemotherapy in High-risk Upper Tract Urothelial Carcinoma With an ERBB2 Gene Mutation: A Case Report.

In bladder urothelial carcinoma, ERBB2 mutations have been associated with favorable response to platinum-based neoadjuvant chemotherapy. However, this association has not been reported in upper tract urothelial carcinoma (UTUC). We describe an excellent response to cisplatin-based chemotherapy in metastatic UTUC with an ERBB2 mutation. Our patient is a 54-year-old female with metastatic UTUC who received systemic cisplatin and gemcitabine. Postchemotherapy imaging demonstrated decreased size of pyelocaliceal mass and decreased retroperitoneal adenopathy compared to initial imaging. Surgical pathology from consolidative resection showed 3 mm residual renal tumor and no viable lymph node disease. Genomic testing demonstrated an ERBB2 gain of function mutation.

The effect of treatment on work productivity in patients with bladder cancer.

OBJECTIVE: To describe the impact of bladder-preserving treatment vs. cystectomy on work productivity and activity impairment (WPAI) among patients with bladder cancer. METHODS: Using cross-sectional survey data, we constructed 2-part models involving both logistic and linear prediction to describe the relationship between WPAI and treatment modality among patients with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). RESULTS: A total of 848 patients were included in the analysis. Patients with NMIBC who had cystectomy were more likely to experience activity impairment compared with those receiving bladder-preserving treatment (OR: 4.25, 95% CI: 2.28-7.93). Among patients with MIBC, cystectomy was protective against increasing presenteeism (e^ß: 0.41, 95% CI: 0.23-0.71) and productivity loss (e^ß: 0.44, 95% CI: 0.21-0.88); however, the opposite effect was seen for absenteeism treatment (e^ß: 4.82, 95% CI: 1.72-13.49). CONCLUSION: Cystectomy increased the odds of experiencing activity impairment for patients with NMIBC. However, for patients with MIBC, cystectomy appears to be protective for presenteeism and productivity loss. Further work is needed in order to better understand these important relationships and improve both patient counseling and shared decision-making.

Molecular characterization of plasmacytoid urothelial carcinoma and the impact on treatment implications.

Bladder cancer researchers and clinicians have increasingly viewed tumor biology through the lens of genomic and molecular alterations, drastically improving our knowledge of the underlying disease biology. This understanding has led to significant advances in treatment options that allow implementation of a personalized approach to cancer treatment. Large-scale genomic studies initially focused on the most common forms of bladder cancer. However, as genomic and molecular technologies become more widespread and are applied to less common variant histologies, we are gaining additional insight into the unique molecular and genomic characteristics driving the biology of variant histologies of bladder cancer. In this review, we summarize the current state of knowledge of molecular alterations underlying the distinct tumor biology of plasmacytoid urothelial carcinoma and how these alterations may impact treatment options.

PBRM1 Inactivation Promotes Upregulation of Human Endogenous Retroviruses in a HIF-Dependent Manner.

Clear cell renal cell carcinoma (ccRCC) is considered an immunotherapy-responsive disease; however, the reasons for this remain unclear. Studies have variably implicated PBRM1 mutations as a predictive biomarker of immune checkpoint blockade (ICB) response, and separate studies demonstrate that expression of human endogenous retroviruses (hERV) might be an important class of tumor-associated antigens. We sought to understand whether specific mutations were associated with hERV expression. Two large, annotated genomic datasets, TCGA KIRC and IMmotion150, were used to correlate mutations and hERV expression. PBRM1 mutations were consistently associated with increased hERV expression in primary tumors. In vitro silencing of PBRM1, HIF1A, and HIF2A followed by RNA sequencing was performed in UMRC2 cells, confirming that PBRM1 regulates hERVs in a HIF1α- and HIF2α-dependent manner and that hERVs of the HERVERI superfamily are enriched in PBRM1-regulated hERVs. Our results uncover a role for PBRM1 in the negative regulation of hERVs in ccRCC. Moreover, the HIF-dependent nature of hERV expression explains the previously reported ccRCC-specific clinical associations of PBRM1-mutant ccRCC with both a good prognosis as well as improved clinical outcomes to ICB. See related Spotlight by Labaki et al., p. 274.

Quality of Life and Health State Utilities in Bladder Cancer.

BACKGROUND: Bladder cancer treatments may variably impact health-related quality of life (QOL). OBJECTIVE: To characterize the quality of life of patients with bladder cancer at various time points across the continuum of bladder cancer care from non-muscle-invasive disease to metastatic bladder cancer and develop utility scores to inform cost-effective analyses. METHODS: We performed a cross-sectional survey of bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network. Participants were classified into mutually exclusive health states based upon non-muscle invasive (NMIBC), muscle-invasive (MIBC), or metastatic bladder cancer and completed surveys of generic cancer and bladder cancer-specific quality of life, financial toxicity, and work impairment. We constructed generalized linear mixed models to identify patient, clinical, and treatment factors associated with quality of life over time and derived health state utilities. RESULTS: Among 911 self-identified patients with bladder cancer, overall QOL scores and function domains were worse among those with advanced cancer. Financial toxicity was similar among non-metastatic disease states. Work and activity impairment increased with advancing disease (13%and 12%among non-recurrent NMIBC to 63%and 31%for metastatic disease respectively; p < 0.01). On multivariable analysis, bowel-related QOL was diminished among patients with MIBC, with urinary symptoms and physical function most diminished among patients with metastatic disease. Patients with metastatic and MIBC experienced worse emotional functioning (p = 0.04; p = 0.048). Health state utilities were calculated, highest among those with non-recurrent NMIBC and lowest among those with metastatic disease. CONCLUSION: Generic and bladder cancer-specific QOL diminishes with advancing disease. Health state utility estimates derived from this study can inform shared decision making with patients and may be used to inform future cost-effective analyses.

Implementation of Postoperative Standard Opioid Prescribing Schedules Reduces Opioid Prescriptions Without Change in Patient-reported Pain Outcomes.

OBJECTIVE: To implement Standard Opioid Prescribing Schedules (SOPS) based on opioid use following urologic surgeries and to evaluate how evidence-based prescribing schedules affect opioid use and patient reported outcomes. METHODS: Patients who underwent urologic surgeries within 6 procedure subtypes at UNC Health during the 2 study time periods ("pre-SOPS": 7/2017-1/2018, "post-SOPS": 7/2018-1/2019) were invited to complete a survey analyzing postoperative opioid usage, storage and disposal, and patient reported outcomes (including pain interference using a validated questionnaire). A pharmacy database provided medication prescribing data and patient demographics. During the pre-SOPS time period, baseline outcomes were measured. Following the pre-SOPS period, usage amounts were analyzed and Standard Opioid Prescribing Schedules were developed to guide prescriptions during the post-SOPS period. Descriptive summary statistics and appropriate t test or r2 were calculated. RESULTS: A total of 438 patients within 6 procedure types completed the survey (pre-SOPS: 282 patients, post-SOPS: 156 patients). Pre-SOPS, patients were prescribed significantly more 5-mg oxycodone tablets than used (20.9 vs 7.8, P <.001). Post-SOPS, compared to pre-SOPS amounts, patients were prescribed significantly fewer tablets (12.7 vs 20.9, P <.001) and used fewer tablets (5.3 vs 7.8, P = .003). No difference was observed in pain interference (average t-score (standard deviation): 54.33 (10.9) pre-SOPS vs 55.89 (9.1) post-SOPS, P = .125) or patient satisfaction (95% pre-SOPS vs 94% post-SOPS). CONCLUSION: Adherence to data-driven postoperative opioid prescribing schedules reduce opioid prescriptions and use without compromising pain interference or patient satisfaction. These results have important implications for urologists' ability to decrease opioid prescriptions and fight the opioid epidemic.

Correction: SETD2 loss sensitizes cells to PI3Kß and AKT inhibition.

[This corrects the article DOI: 10.18632/oncotarget.26567.].

SETD2 loss sensitizes cells to PI3Kß and AKT inhibition.

Upregulation of the PI3K pathway has been implicated in the initiation and progression of several types of cancer, including renal cell carcinoma (RCC). Although several targeted therapies have been developed for RCC, durable and complete responses are exceptional. Thus, advanced RCC remains a lethal disease, underscoring the need of robust biomarker-based strategies to treat RCC. We report a synthetic lethal interaction between inhibition of phosphatidylinositol 3-kinase beta (PI3Kß) and loss of SETD2 methyltransferase. Clear cell RCC (ccRCC)-derived SETD2 knockout 786-0 and SETD2 mutant A498 cells treated with TGX221 (PI3Kß-specific) and AZD8186 (PI3Kß- and δ-specific) inhibitors displayed decreased cell viability, cell growth, and migration compared to SETD2 proficient 786-0 cells. Inhibition of the p110 δ and α isoforms alone had modest (δ) and no (α) effect on ccRCC cell viability, growth, and migration. In vivo, treatment of SETD2 mutant A498 cells, but not SETD2 proficient 786-0 cells, with AZD8186 significantly decreased tumor growth. Interestingly, inhibition of the downstream effector AKT (MK2206) recapitulated the effects observed in AZD8186-treated SETD2 deficient cells. Our data show that specific inhibition of PI3Kß causes synthetic lethality with SETD2 loss and suggest targeting of the AKT downstream effector pathway offers a rationale for further translational and clinical investigation of PI3Kß-specific inhibitors in ccRCC.