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Objective To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

Background Testicular cancer survivors (TCS) are at increased risk of cancer-related fatigue (CRF), psychosocial impairment, and poor mental health-related quality of life (HRQoL). Here, we examine the effects of high-intensity interval training (HIIT) on patient-reported outcomes (PROs) in TCS. Secondarily, we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects. Methods TCS (n = 63) were randomly assigned to 12 weeks of supervised HIIT or usual care (UC). PROs included CRF, depression, anxiety, stress, self-esteem, sleep quality, and HRQoL assessed at baseline, post-intervention, and 3-month follow-up. Results TCS (median 7 years postdiagnosis) completed 99% of training sessions and achieved 98% of target training intensity. ANCOVA revealed that, compared to UC, HIIT significantly improved post-intervention CRF (p = 0.003), self-esteem (p = 0.029), and multiple HRQoL domains (ps ≤ 0.05). Effects on CRF (p = 0.031) and vitality (p = 0.015) persisted at 3-month follow-up. Cardiorespiratory fitness changes mediated CRF and HRQoL improvements. CRF effects were larger for TCS with an inactive lifestyle, lower fitness, higher testosterone, and clinical fatigue at baseline. Conclusions HIIT significantly improves CRF and HRQoL in TCS. Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS.

Background Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies. Objective To assess the changes in 5-yr CS rates after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to determine how well-established prognostic factors evolve over time. Design, setting, and participants We analysed data from 3544 patients treated with RNU at 15 international academic centres between 1989 and 2012. Intervention RNU. Outcomes measurements and statistical analysis Conditional intravesical recurrence-free (IVRFS), cancer-specific survival (CSS), and overall survival (OS) estimates were calculated using the Kaplan-Meier method. A multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality. Results and limitations The 5-yr bladder cancer recurrence-free survival, CSS, and OS rates were 54.9%, 72.2%, and 62.6%, respectively. Given a 1-, 2-, 3-, and 4-yr survivorship, the 5-yr conditional OS rates improved to 65.2%, 69.3%, 71.5%, and 73.0%, respectively. The 5-yr CS improvement was primarily noted among surviving patients with advanced-stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS, whereas the impact of age and gender increased with survivorship. No survival benefit was noted regarding the adjuvant chemotherapy status. Findings were confirmed upon multivariable analyses. Tumour location, the presence of carcinoma in situ, and the type of bladder cuff excision were continuously predictive for IVRFS whatever the survivorship. A limitation is the retrospective design. Conclusions CS analysis demonstrates that the patient risk profile evolves during the post-RNU follow-up. The probability of survival markedly increases over time in patients having high-stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS. Patient summary In this study, we found that the risk of intravesical recurrence, cancer-specific survival, and overall mortality evolves over the follow-up after surgery. Taking into account the survivorship provides better estimates of the survival probability at each follow-up time.

Objective To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. Patients and methods We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. Results In all patients (Tall N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3–4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. Conclusions AC seems to reduce mortality in patients with pT3–4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

Introduction: We delineated Canadian regional differences in practice patterns in the management of upper tract urothelial carcinoma (UTUC) after nephroureterectomy and relate these to patient outcomes.Methods: A database was created with 1029 patients undergoing radical nephroureterectomy for UTUC between 1994 and 2009 at 10 Canadian centres. Demographic, clinical and pathological variables were collected from chart review. Practice pattern variables were defined as: open versus laparoscopic nephroureterectomy, management strategy for the distal ureter, performance of lymphadenectomy and administration of chemotherapy and/or radiation therapy. The outcome measures were overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). The centres were divided into three regions (West, Central, East). Cox proportional multivariable linear regression analysis was used to determine the association between regional differences in practice patterns and clinical outcomes.Results: There was a significant difference in practice patterns between regions within Canada for: time from diagnosis to surgery (p = 0.001), type of surgery (open vs. laparoscopic, p < 0.01) and method of management of the distal ureter (p = 0.001). As well, there were significant differences in survival between regions across Canada: 5-year OS (West 70%, Central 81% and East 62%, p < 0.0001) and DSS (West=79%, Central=85%, East=75%, p = 0.007) were significantly different, but there was no difference in RFS (West 47%, Central 48%, East 46%, p = 0.88). Multivariable linear regression analysis demonstrated that the differences in survival were independent of region OS (p = 0.78), DSS (p = 0.30) or RFS (p = 0.43).Conclusion: There is significant disparity in practice patterns between regions within Canada, but these do not appear to have an effect on survival. We believe that the variability in practice is a reflection of the lack of standardized treatments for UTUC and underlines the need for multi-institutional studies in this disease.

Introduction: The objective of this study was to compare referral and treatment rates of neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer before and after publication of a clinical practice guideline. Methods: This was a retrospective comparative cohort study of 236 patients diagnosed with clinical stage ≥ T2 bladder cancer in Alberta, Canada. Patients were divided into 2 groups based on the time of diagnosis relative to the publication of the Alberta Genitourinary Oncology Group Clinical Practice Guideline on Bladder Cancer (CPG), which recommends cisplatin-based neoadjuvant chemotherapy for muscle-invasive disease. The pre-CPG group included patients (n = 129) diagnosed prior to publication of the CPG (November 1, 2002 to October 31, 2004, inclusively). The post-CPG group included patients (n = 107) diagnosed after publication of the CPG (November 1, 2005 to October 31, 2007). There was an accrual blackout period of 6 months before and after the CPG release date. The primary analysis compared the two groups with respect to neoadjuvant chemotherapy referral rates, treatment-offered rates and treatment-administered rates. Results: Referral to medical oncology regarding neoadjuvant chemotherapy occurred in 2.3% and 23.4% of patients in the pre- and post-CPG groups, respectively (p < 0.01). Neoadjuvant chemotherapy was offered to 0.8% and 18.7% of patients in the pre- and post-CPG groups, respectively (p < 0.01). Neoadjuvant chemotherapy was administered to 0.8% and 14.0% of patients in the pre- and post-CPG groups, respectively (p < 0.01). Interpretation: Neoadjuvant referral and treatment rates increased after publication of the CPG. However, overall referral and treatment rates remained low, which warrants additional exploration. Introduction : L’objectif de l’etude etait de comparer les taux de recommandation et de traitement par chimiotherapie neoadjuvante chez les patients atteints de cancer de la vessie avec envahissement musculaire avant et apres la publication d’un guide de pratique clinique. Methodologie : Il s’agit ici d’une etude comparative retrospective de cohorte comptant 236 patients de l’Alberta, au Canada, chez qui on avait diagnostique un cancer de la vessie de stade clinique T2 ou pire. Les patients ont ete repartis en 2 groupes selon que leur diagnostic avait ete pose avant ou apres la publication du guide de pratique clinique sur le cancer de la vessie (GPC) de l’Alberta Genitourinary Oncology Group, qui recommande une chimiotherapie neoadjuvante a base de cisplatine pour le traitement des cas de cancer avec envahissement musculaire. Le groupe pre-GPC comprenait des patients (n = 129) chez qui le diagnostic avait ete pose avant la publication du GPC (du 1er novembre 2002 au 31 octobre 2004, inclusivement). Le groupe post-GPC incluait des patients (n = 107) chez qui le diagnostic avait ete pose apres la publication du GPC (du 1er novembre 2005 au 31 octobre 2007). Une periode cumulative de censure a ete calculee 6 mois avant et apres la date de publication du GPC. L’analyse preliminaire a compare les deux groupes quant aux taux de recommandation de la chimiotherapie neoadjuvante, aux taux d’offre et d’administration du traitement. Resultats : La chimiotherapie neoadjuvante a ete recommandee chez 2,3 et 23,4 % des patients dans les groupes pre-GPC et post-GPC, respectivement (p < 0,01). Elle a ete offerte a 0,8 % et 18,7 % des patients de ces memes groupes (p < 0,01), et administree a 0,8 et 14,0 % des patients des groupes pre-GPC et post-GPC, respectivement (p < 0,01). Interpretation : Les taux de recommandation et de traitement concernant la chimiotherapie neoadjuvante ont augmente apres la publication du GPC, mais sont tout de meme demeures faibles, ce qui necessite une analyse plus poussee.