Background and objectiveThe rationale for oophorectomy during female cystectomy is not adequately supported. The co-occurrence and timing of bladder cancer (BC) and ovarian cancer (OC) in females harboring OC germline mutations remain unclear. Our objective was to determine the frequency and temporal occurrence of OC germline variants among females with BC.MethodsWe used genetic and phenotypic data from the UK Biobank (UKB). The study cohort was defined using ICD-10/ICD-9 codes for BC and further stratified to identify 1347 females. Analysis was restricted to variants with high/moderate impact for initial regression. ClinVar was used to interpret pathogenicity. Pathogenic/likely pathogenic (P/LP) variants were assessed by age of presentation, family history, and concomitant malignancies. Statistical analysis was performed using UKB DNAnexus JupyterLab and RStudio.Key findings and limitationsSome 3.4% of the patients had at least one of 15 variants for OC. CHEK2 and PALB2 mutations represented the highest ratio of overall/pathogenic variants (15.8% and 6.6%). Although females with P/LP OC mutations had a higher risk of OC, diagnosis of OC preceded BC by 11.3 yr (±12.5 yr) in the group with mutations and by 15.6 yr (±11.3 yr) in the group without mutations. The group with P/LP variants had higher rates of maternal (14.63% vs 8.12%; p = 0.04) and sibling (9.76% vs 3.98%; p = 0.02) breast cancer and of maternal colon cancer (9.76% vs 4.21%), and lower maternal life expectancy (75.34 vs 68.15 yr; p = 0.0014). UKB provides limited staging/treatment history and its exome sequencing platform may miss variants or provide insufficient coverage for genotyping.Conclusions and clinical implicationsThis study provides evidence against routine oophorectomy for reducing OC risk in females with BC. The results highlight that the development of OC occurred 11 yr before diagnosis of BC for patients with OC mutations and 15 yr before diagnosis of BC for patients without OC mutations.Patient summaryAlthough removal of the ovaries in women with bladder cancer is common, no studies have shown that this strategy has a benefit. Our study of women diagnosed with bladder cancer who had genetic mutations associated with ovarian cancer shows that their risk of developing ovarian cancer after bladder cancer is low. These findings provide evidence against removal of the ovaries when the bladder is being removed as treatment for bladder cancer.
•22 trials involving 12,727 patients with advanced solid organ malignancies were included in this meta-analysis.•Patients receiving immunotherapy were less likely to develop severe adverse events than those receiving chemotherapy.•Fewer terminations due to adverse events or deaths due to adverse events occurred in the immunotherapy group.•Fatigue and diarrhea were more likely to occur in patients treated with chemotherapy. BackgroundImmunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice.DesignA systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule–Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects.ResultsAmong 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19–0.35, I2 = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28–0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39–0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46–0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy.ConclusionsTreatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs. Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice. A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule–Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects. Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19–0.35, I2 = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28–0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39–0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46–0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy. Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.
Background: The causal association between radiation and chemotherapy treatment and the development of secondary sarcoma is well known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Methods: We conducted a population–based retrospective cohort study examining the risk of sarcoma among patients with localized cancer of the prostate, bladder, colorectal, cervical, uterine, and testis between 2002–2016. The primary outcome was the development of sarcoma. Cox proportional hazard analysis was used to estimate the risk of sarcoma after treatment combinations with radiation, chemotherapy, or surgery. Findings: We identified 173,580 patients. Most patients had genitourinary (51∙4%) or colorectal cancer (39∙9%). Overall, 332 (0∙2%) sarcomas developed over a median of 5∙7 years (IQR: 2∙2–8∙9). Compared to a reference group of patients who had surgery alone, the greatest risk for sarcoma was found for patients who underwent a combination of radiation and chemotherapy (HR=4∙1,95%CI:2∙8–6∙0,p<0∙001). This was followed by patients who had radiation alone (HR=2∙4,95%CI:1∙8–3∙1,p<0∙001), radiation with surgery (HR=2∙3,95%CI:1∙6–3∙5,p<0∙001), and all three modalities (HR=2∙3,95%CI:1∙4–3∙6,p<0∙001). The standardized incidence ratio for sarcoma among patients treated with radiation compared to the general population was 2∙4 (95%CI:1∙6–3∙7). The annual number of cases of sarcoma increased from 2009 (15 per 100,000 persons) to 2016 (32 per 100,000 persons), but the annual rate did not change over time. Interpretation: Patients treated with radiation and chemotherapy for abdominopelvic cancers had an increased risk of sarcoma. The number of cases is increasing per year due to longer survival from the treatment of the initial cancer.Funding Statement: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long–Term Care. This study also received funding from the Ajmera Family Chair in Urologic Oncology awarded to RKN.Declaration of Interests: GSK has acted as a consultant for Merck, Roche, Janssen and Ferring and received honoraria for lectures on behalf of Biosyent, Merck, Roche and Theralase. SH reports receiving grants from Astellas Pharma Canada, Allergan, AMI, Boston Scientific, and Pfizer all outside the submitted work. All other authors have no conflicts of interest to declare.Ethics Approval Statement: The study was approved by the Sunnybrook Research Ethics Board.
ObjectiveTo characterize academic urology Twitter presence and interaction by subspecialty designation.MethodsUsing Twitter application programming interface of available data, 94000 specific tweets were extracted for the analysis through the Twitter Developer Program. Academic urologists were defined based on American Urological Association (AUA) residency program registration of 143 residency programs, with a total of 2377 faculty. Two of 3-factor verification (name, location, specialty) of faculty Twitter account was used. Additional faculty information including sex, program location, and subspecialty were manually recorded. All elements of microblogging were captured through Anaconda Navigator. Analyzed tweets were further evaluated using natural language processing for sentiment association, mentions, and quote tweeted and retweeted. Network analysis based on interactions of academic urologist within specialty for given topic were analyzed using D3 in JavaScript. Analysis was performed in Python and R.ResultsWe identified 143 residency programs with a total of 2377 faculty (1975 men and 402 women). Among all faculty, 945 (39.7%) had registered Twitter accounts, with the majority being men (759 [80.40%] versus 185 [19.60%]). Although there were more male academic urologists across programs, women within academic urology were more likely to have a registered Twitter account overall (46% versus 38.5%) compared with men. When assessing registered accounts by sex, there was a peak for male faculty in 2014 (10.05% of all accounts registered) and peak for female faculty in 2015 (2.65%). There was no notable change in faculty account registration during COVID-19 (2019–2020). In 2022, oncology represented the highest total number of registered Twitter users (225), with the highest number of total tweets (24622), followers (138541), and tweets per user per day (0.32). However, andrology (50%) and reconstruction (51.3%) were 2 of the highest proportionally represented subspecialties within academic urology. Within the context of conversation surrounding a specified topic (#aua21), female pelvic medicine and reconstructive surgery (FPMRS) and endourology demonstrated the total highest number of intersubspecialty conversations.ConclusionsThere is a steady increase in Twitter representation among academic urologists, largely unaffected by COVID-19. While urologic oncology represents the largest group, andrology and reconstructive urology represent the highest proportion of their respective subspecialties. Interaction analysis highlights the variant interaction among subspecialties based on topic, with strong direct ties between endourology, FPMRS, and oncology.
Radical cystectomy and trimodal therapy are both accepted options in the management of muscle-invasive bladder cancer. As such, we sought to evaluate the micro-level costs associated with both modalities.All patients undergoing trimodal therapy or radical cystectomy for primary treatment of urothelial muscle-invasive bladder cancer at a single academic center between 2008 and 2012 were included. Direct costs associated with each phase of a patient's clinical course were collected from the hospital's financial department, and physician costs were calculated based on the provincial fee schedule. Costs of radiation treatments were derived from previously published literature.A total of 137 patients were included. The mean (±SD) patient age was 69 (±12) years. Overall, 89 (65%) patients underwent radical cystectomy and 48 (35%) were treated with trimodal therapy. The radical cystectomy group had higher rates of cT3/T4 compared to those in the trimodal therapy group (51% vs 26%, P < .001). The median cost in the treatment phase for radical cystectomy was $30,577 (IQR: $23,908-$38,837) vs $18,979 ($17,271-$23,519) for trimodal therapy (P < .001). There was no significant difference between treatment groups with respect to cost of diagnosis or workup. However, the cost of follow-up care was numerically higher for patients undergoing trimodal therapy compared to radical cystectomy ($3,096/y vs $1,974/y, P = .09).In appropriately selected patients with muscle-invasive bladder cancer trimodal therapy costs are not prohibitive and are lower than in radical cystectomy. With increasing follow-up time after primary treatment, the cost difference between modalities may be mitigated by the need for bladder surveillance and salvage therapy in the trimodal therapy cohort.
508 Background: Upper tract urothelial carcinoma (UTUC) accounts for less than 5% of all urothelial cancers. As a result, this disease is clinically understudied and there are no definitive recommendations regarding use and timing of peri-operative chemotherapy. The objective of this study was to create a decision model comparing three treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC). Methods: A Markov microsimulation model was constructed using TreeAge Pro to compare treatment strategies for patients with newly diagnosed UTUC. Our primary outcome was quality adjusted life expectancy (QALE). Secondary outcomes included rates of adverse chemotherapy events, bladder cancer diagnoses, and crude survival. Markov cycle length was 3 months to mimic the follow up interval used in clinical practice for patients with UTUC. A systematic literature review was used to generate probabilities to populate the model. The base case was a 70-year-old patient with a radiographically localized upper tract tumor. Patients could have evidence of nodal disease, but no distant metastasis. Results: A total of 100,000 microsimulations were generated. NAC was preferred with an estimated QALE of 7.52 years versus 6.80 years with NU alone and 7.20 years with AC. Overall, 39.6% of patients in the AC group with invasive pathology received and were able to complete chemotherapy. A total of 37.5% of patients in the NAC group experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 66.0%, and 67.1% over the patient’s lifetime in the NU, NAC, and AC groups, respectively. Conclusions: This study provides evidence to support the increased use of NAC in UTUC until robust randomized trials can be completed. While the use of NAC in this population appears favourable, the ultimate choice rests with the clinician and should be based on patient and tumor factors.
