The Impact of Histologic Subtypes on Clinical Outcomes After Radiation-Based Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: Outcomes of radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC) with histologic subtypes of urothelial cancer (HS-UC) are lacking. Our objective was to compare survival outcomes of pure urothelial carcinoma (PUC) to HS-UC after RT. MATERIALS AND METHODS: A multicenter retrospective study of 864 patients with MIBC who underwent curative-intent RT to the bladder for MIBC (clinical T2-T4aN0-2M0) between 2001 and 2018 was conducted. Regression models were used to test the association between HS-UC and complete response (CR) and survival outcomes after RT. RESULTS: In total, 122 patients (14%) had HS-UC. Seventy-five (61%) had HS-UC with squamous and/or glandular differentiation. A CR was confirmed in 69% of patients with PUC and 63% with HS-UC. There were 207 (28%) and 31 (25%) patients who died of metastatic bladder cancer in the PUC and HS-UC groups, respectively. There were 361 (49%) and 58 (48%) patients who died of any cause in the PUC and HS-UC groups, respectively. Survival outcomes were not statistically different between the groups. The HS-UC status was not associated with survival outcomes in multivariable Cox regression analyses. CONCLUSIONS: In our study, HS-UC responded to RT with no significant difference in CR and survival outcomes compared to PUC. The presence of HS-UC in MIBC does not seem to confer resistance to RT, and patients should not be withheld from bladder preservation therapy options. Due to low numbers, definitive conclusions cannot be drawn for particular histologic subtypes.

Effect of Complete Transurethral Resection on Oncologic Outcomes After Radiation Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: To compare the oncologic outcomes of patients with nonmetastatic muscle-invasive bladder cancer (MIBC) undergoing complete versus incomplete transurethral tumor resection (TURBT) before radiation therapy. METHODS AND MATERIALS: Patients with nonmetastatic MIBC who underwent curative-intent radiation therapy between 2002 and 2018 at 10 Canadian institutions were retrospectively evaluated. Inverse probability of treatment weighting was performed using baseline characteristics. Differences in survival outcomes by complete and incomplete TURBT were analyzed. RESULTS: Of the 757 patients included, 66% (498) had documentation of a complete and 34% (259) an incomplete TURBT. Before adjustment, 121 (47%) and 45 (9%) patients who underwent incomplete and complete TURBT, respectively, were diagnosed with cT3-4 tumor (P <.001). After weight-adjustment, all baseline cohort characteristics were balanced (absolute standardized differences < 0.1). The adjusted median follow-up was 27 months. Adjusted survival analyses showed no significant difference in 5-year overall survival (48% vs 52%, 1.03 [0.82-1.29]; P = .8), cancer-specific survival (64% vs 61%, 0.93 [0.70-1.25]; P = .7), metastasis-free survival (43% vs 46%, 0.97 [0.79-1.19]; P = .8), and disease-free survival (32% vs 35%, 0.95 [0.79-1.15]; P = .7) between the 2 groups. CONCLUSIONS: Complete TURBT may be associated with clinical organ-confined disease. Extent of TURBT was not independently associated with oncologic outcomes in patients with MIBC treated with radiation therapy.

Benefit of Whole-Pelvis Radiation for Patients With Muscle-Invasive Bladder Cancer: An Inverse Probability Treatment Weighted Analysis.

PURPOSE: The value of pelvic lymph node irradiation is debated for patients with muscle-invasive bladder cancer (MIBC) undergoing curative-intent radiation therapy (RT). We sought to compare the oncological outcomes between bladder-only (BO)-RT and whole-pelvis (WP)-RT using a large Canadian multicenter collaborative database. PATIENTS AND METHODS: The study cohort consisted of 809 patients with MIBC (cT2-4aN0-2M0) who underwent curative RT at academic centers across Canada. Patients were divided into two groups on the basis of the RT volume: WP-RT versus BO-RT. Inverse probability of treatment weighting (IPTW) and absolute standardized differences (ASDs) were used to balance covariates across treatment groups. Regression models were used to assess the effect of the RT volume on the rates of complete response (CR), cancer-specific survival (CSS), and overall survival (OS). RESULTS: After exclusion criteria, 599 patients were included, of whom 369 (61.6%) underwent WP-RT. Patients receiving WP-RT were younger (ASD, 0.41) and more likely to have an Eastern Cooperative Oncology Group performance status of 0-1 (ASD, 0.21), clinical node-positive disease (ASD, 0.40), and lymphovascular invasion (ASD, 0.25). In addition, WP-RT patients were more commonly treated with neoadjuvant chemotherapy (ASD, 0.29) and concurrent chemotherapy (ASD, 0.44). In the IPTW cohort, BO-RT and WP-RT groups were well balanced (all pretreatment parameters with an ASD <0.10). In multivariable analysis, WP-RT was not associated with CR rates post-RT (odds ratio, 1.14 [95 CI, 0.76 to 1.72]; P = .526) but was associated with both CSS (hazard ratio [HR], 0.66 [95% CI, 0.47 to 0.93]; P = .016) and OS (HR, 0.68 [95% CI, 0.54 to 0.87]; P = .002), independent of other prognostic factors. CONCLUSION: Our study demonstrated that WP radiation was associated with better survival compared with bladder radiation alone after adjusted analysis. Additional randomized controlled trials are needed to confirm our findings.

Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) improves survival for patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. Studies on the potential benefit of NAC before radiation-based therapy (RT) are conflicting. OBJECTIVE: To evaluate the effect of NAC on patients with MIBC treated with curative-intent RT in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: The study cohort consisted of 785 patients with MIBC (cT2-4aN0-2M0) who underwent RT at academic centers across Canada. Patients were classified into two treatment groups based on the administration of NAC before RT (NAC vs no NAC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The inverse probability of treatment weighting (IPTW) with absolute standardized differences (ASDs) was used to balance covariates across treatment groups. The impact of NAC on complete response, overall, and cancer-specific survival (CSS) after RT in the weighted cohort was analyzed. RESULTS AND LIMITATIONS: After applying the exclusion criteria, 586 patients were included; 102 (17%) received NAC before RT. Patients in the NAC subgroup were younger (mean age 65 vs 77 yr; ASD 1.20); more likely to have Eastern Cooperative Oncology Group performance status 0-1 (87% vs 78%; ASD 0.28), lymphovascular invasion (32% vs 20%; ASD 0.27), higher cT stage (cT3-4 in 29% vs 20%; ASD 0.21), and higher cN stage (cN1-2 in 32% vs 4%; ASD 0.81); and more commonly treated with concurrent chemotherapy (79% vs 67%; ASD 0.28). After IPTW, NAC versus no NAC cohorts were well balanced (ASD <0.20) for all included covariates. NAC was significantly associated with improved CSS (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.14-0.56; p < 0.001) and overall survival (HR 0.56; 95% CI 0.38-0.84; p = 0.005). This study was limited by potential occult imbalances across treatment groups. CONCLUSIONS: If tolerated, NAC might be associated with improved survival and should be considered for eligible patients with MIBC planning to undergo bladder preservation with RT. Prospective trials are warranted. PATIENT SUMMARY: In this study, we showed that neoadjuvant chemotherapy might be associated with improved survival in patients with muscle-invasive bladder cancer who elect for curative-intent radiation-based therapy.

Radiation-based Therapy for Muscle-invasive Bladder Cancer: Contemporary Outcomes Across Tertiary Centers.

BACKGROUND: Radiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To analyze predictors of complete response (CR) and survival after RT for MIBC. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS: The median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3-4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034-0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46-2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25-3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79-3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46-0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51-0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01-1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34-2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17-1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49-0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51-0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12-1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols. CONCLUSIONS: RT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation. PATIENT SUMMARY: We investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study.

Comparison of diagnostic accuracy of computed tomography virtual endoscopy and flexible fibre-optic laryngoscopy in the evaluation of neck anatomic structures and neoplasms.

BACKGROUND AND PURPOSE: Computed tomography virtual endoscopy (CT-VE) is a non-invasive technique which allows visualisation of intraluminal surfaces by tridimensional reconstruction of air/soft tissues. The aim of this study was to compare the diagnostic accuracy of CT-VE and flexible fibre-optic laryngoscopy (FFL) in identifying normal neck anatomic structures and pharyngeal and laryngeal lesions. METHODS: Forty-two patients with a history of neck cancer were assessed by two ENT surgeons using FFL and by one neuroradiologist using CT-VE in order to evaluate the visualisation of the epiglottis, vallecula, glossoepiglottic folds, pyriform sinuses, vocal cords and mass pathology. The visualisation of the structures in both modalities was assessed according to the following score: 0 = not visualised, 1 = partial visualisation, 2 = complete and clear visualisation. A weighted kappa coefficient was used to evaluate the inter-observer agreement. McNemar's test was performed to compare the two diagnostic tests. RESULTS: The inter-observer agreement between FFL and CT-VE was fair in the assessment of the vocal cords (k = 0.341); moderate in the assessment of the glossoepiglottic folds (k = 0.418), epiglottis (k = 0.513) and pyriform sinuses (k = 0.477); and substantial in the assessment of the vallecula (k = 0.618) and the tumour (0.740). McNemar's test showed no significant difference between the two tests (p<0.05). CONCLUSION: CT-VE is a non-invasive technique with a diagnostic accuracy comparable to FFL in terms of visualisation of anatomical structures and pharyngeal and laryngeal lesions.