Efficacy of Pembrolizumab in Patients With Variant Urothelial Carcinoma: A Multicenter Retrospective Study

IntroductionAlthough variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease.Patients and MethodsWe retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC.ResultsWe identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n = 14) was the most common variant element, followed by glandular differentiation (n = 3) and micropapillary variant (n = 3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P = .014) and comparable DCR (68.2% vs. 49.4%, P = .150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P = .222) or OS (median 13.5 months vs. 23.8 months, P = .497).ConclusionResponse of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer.     

Unfavorable Cancer-specific Survival After Neoadjuvant Chemotherapy and Radical Cystectomy in Patients With Bladder Cancer and Squamous Cell Variant: A Multi-institutional Study

BackgroundNonurothelial carcinoma (UC) malignancies have traditionally been considered to have a more aggressive clinical course, and little is known about their response to neoadjuvant therapy. We examined the effect of neoadjuvant chemotherapy (NAC) on a large population of patients with bladder cancer (BCa) with different histologic variants (HVs).Patients and MethodsWe relied on a retrospective, multicenter database of 2858 patients with BCa who had undergone radical cystectomy with or without NAC from 1990 to 2017. Pure and mixed HVs were grouped into 6 categories: squamous cell carcinoma (SCC; n = 283; 45%), other subtypes (n = 95; 15%), micropapillary (n = 85; 14%), adenocarcinoma (n = 65; 10%), small cell (n = 54; 8.6%), and sarcomatous (n = 47; 7.6%). Kaplan-Meier and Cox regression analyses were used to examine cancer-specific survival (CSS) according to the HV, using pure UC as the reference. Logistic regression models were used to examine the odds of clinical-to-pathologic downstaging after NAC according to the HV.ResultsOverall, we identified 2229 cases of pure UC and 629 cases of BCa with HVs at radical cystectomy. Of the 450 NAC-treated patients, only those patients with SCC (n = 44; 9.8%) had had worse CSS (median CSS, 33 vs. 116 months; P < .001) and higher mortality rates (hazard ratio, 2.1; P = .03) compared with those with pure UC (n = 328; 72.9%). The results of the analyses were also confirmed when the pure and mixed cases were considered separately. After adjusting for NAC, only SCC showed a lower rate of clinical-to-pathologic downstaging (odds ratio, 0.4; P = .03) compared with UC.ConclusionsSCC was the HV exhibiting the lowest effect of NAC in terms of activity and CSS. Compared with pure UC, SCC seemed to be insensitive to traditional NAC regimens.     

High-dose Thiotepa,Busulfan, Cyclophosphamide,and Autologous Stem Cell Transplantation as Upfront Consolidation for Systemic Non-Hodgkin Lymphoma With Synchronous Central Nervous System Involvement

IntroductionSynchronous involvement of the central nervous system (CNS) at the diagnosis of systemic non-Hodgkin lymphoma (NHL) is associated with an increased risk for relapse despite complete remission to initial therapy. High-dose chemotherapy with a CNS-directed conditioning regimen followed by autologous stem cell transplantation (ASCT) holds promise as a consolidative approach.Patients and MethodsWe conducted a retrospective analysis of all patients with systemic B-cell NHL and synchronous CNS involvement who received upfront consolidation with high-dose chemotherapy with thiotepa, busulfan, cyclophosphamide, and ASCT while in first complete remission between July 2008 and June 2016 at 2 partner academic institutions.ResultsTwenty patients were identified through the transplant database. The median age at diagnosis was 53 years (range, 37-65 years). The majority had diffuse large B-cell lymphoma histology (n = 17; 85%). The sites of CNS involvement were parenchymal (n = 12; 60%) and leptomeningeal disease (n = 9; 45%). All patients received systemic and CNS-directed therapy prior to transplant, with the most common approaches being R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) (n = 13; 65%) and high-dose intravenous methotrexate (n = 16; 80%), respectively. With a median follow up of 4.4 years after ASCT (range, 2 months-8.5 years), the Kaplan-Meier estimates of 4-year progression-free and overall survival were 77% (95% confidence interval, 48%-91%) and 82% (95% confidence interval, 54%-94%), respectively.ConclusionCNS-directed high-dose chemotherapy and ASCT provides durable remission for patients with synchronous aggressive lymphoma and should be strongly considered as consolidative therapy for eligible patients with systemic NHL with CNS involvement in first complete remission.     

Lymphovascular invasion,ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes

Purpose

To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients.

Methods

We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT_2-3N₀M₀) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival.

Results

With a median follow-up of 53.0 months (range 9–120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder.Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease.The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS.

Conclusions

Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes.     

Bladder Cancer Stage Development, 2004-2014 in Europe Compared With the United States: Analysis of European Population-based Cancer Registries,the United States SEER Database,and a Large Tertiary Institutional Cohort

BackgroundThe purpose of this study was to analyze trends of bladder cancer (BC) stages and incidence in Europe and the United States (US).Materials and MethodsTumor stages after radical cystectomy were assessed in a monocentric cohort from 2006 to 2016. BC incidence was assessed between 2004 and 2014 based on the German Center for Cancer Registry Data dataset at the Robert Koch Institute (n = 111,002), the Netherland Cancer Registry (n = 64,226), cancer registration statistics of England (n = 179,883), and the pooled data from the Scandinavian cancer registries, NORDCAN (n = 77,585) and the SEER (Surveillance, Epidemiology, and End Results) database (n = 184,519) for the complete populations and gender-specific subgroups. The average annual percent changes (AAPC) were used for statistical evaluation.ResultsNon–muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC) did not change in the institutional cohort at the point of radical cystectomy. The incidence of total BC (AAPC, −0.3), NMIBC (AAPC, −0.1), and non-metastasized MIBC (AAPC, 0.1) did not change in Germany during the time period under survey. BC total incidence in the Netherlands did not change significantly. In England and the Nordic countries, the incidence of total BC increased (AAPC, 0.8 and 0.5, respectively). In contrast, both the incidence of total BC (AAPC, −1.4), NMIBC (AAPC, −1.6), and non-metastasized MIBC (AAPC, −1.6) significantly decreased in the US.ConclusionsBetween 2004 and 2014 the incidence of BC was significantly sinking in the US, was stable in Germany and the Netherlands, and increased in England and the Nordic countries. Predominantly, differences in the smoking prevalence within the last decades but also gender-specific factors might be responsible for this discrepancy.     

Significance of Positive Urine Cytology on Progression and Cancer-Specific Mortality of Non–Muscle-Invasive Bladder Cancer

BackgroundPositive results from voided urine cytology (VUC) indicate the fragility of the intercellular adhesion of bladder cancer cells, a critical biological process for invasion and metastasis, along with the presence of atypical cells. Few studies have focused on the prognostic role of VUC in non–muscle-invasive bladder cancer (NMIBC).MethodsBetween 2000 and 2010, 326 patients diagnosed pathologically with Ta or T1 bladder urothelial carcinoma underwent 597 transurethral resections of bladder tumor (TURBTs). Clinicopathological data were prospectively collected at each TURBT. Reports of cells of class IIIb or greater were considered positive VUC results. Muscle-invasive or metastatic recurrences were considered progression. Risk factors for progression and cancer-specific mortality (CSM) were determined using time-fixed and time-dependent Cox models. Variables at the study entry and at each TURBT were used for time-fixed and time-dependent models, respectively.ResultsThe 5-year cumulative progression and CSM rates were, respectively, 7% and 5% (median follow-up, 46 months). The 5-year cumulative progression and CSM rates for patients with positive VUC were 20% and 15%, respectively, compared with 2% (P < .0001) and 2% (P = .0002), respectively, for patients with negative VUC results. A positive VUC result was a significant and independent risk factor for progression and CSM in the time-fixed and time-dependent models. In time-dependent models, 7 predictors for progression or CSM were identified (positive VUC results, T1 disease, lack of intravesical instillation, higher prior recurrence rate, higher histological grade, male gender, and advanced age), whereas 3 predictors were identified in time-fixed models (positive VUC, T1 disease, and higher prior recurrence rate). VUC results consistently outperformed histological grade as a prognostic predictor.ConclusionPositive VUC results predict the progression and CSM of NMIBC, independent of and outperforming histological grade.     

Invasive Bladder Cancer: Our Experience With Bladder Sparing Approach

Purpose: Muscle-invasive bladder cancer (MIBC) is a disease associated with several unresolved therapeutic questions. Radical cystectomy still represents the most frequent treatment approach. The aim of our study was to evaluate the effect and feasibility of bladder-sparing treatment by transurethral resection (TUR) and sequential chemoradiotherapy in patients with biopsy-proven invasive bladder cancer.Methods and Materials: After maximal TUR, 105 patients were treated with two to four cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders, the treatment was continued by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas in nonresponders, cystectomy was performed when feasible.Results: Complete response after TUR and chemotherapy was achieved in 52% of patients. After a median follow-up of 42 months, 52 of 75 patients (69%) selected for bladder preservation were without evidence of disease in the bladder. Freedom from local failure in complete responders to chemotherapy was 80% [95% confidence interval (CI), 69–91%) at 4 years. The actuarial survival of the entire group was 58% (95% CI, 47–69%), whereas the survival rate with the bladder intact was 45% (95% CI, 34–56%) at 4 years. Survival was significantly better in patients who responded to chemotherapy (79%) than in nonresponders (35%, p < 0.0001). There was no significant difference in survival between nonresponders who underwent cystectomy and nonresponders who completed treatment with radiotherapy (approximately 30% at 3 years).Conclusion: The present study confirms that MIBC is a heterogeneous disease, and that in more than half of patients who are affected, a bladder-sparing approach is safe. Our study has also demonstrated that in nonresponders, radical cystectomy as the treatment of choice is questionable.     

Contemporary use and survival after perioperative systemic chemotherapy in patients with locally advanced non-metastatic urothelial carcinoma of the bladder treated with radical cystectomy

BackgroundLocally advanced muscle-invasive bladder cancer (MIBC) patients who are candidates for radical cystectomy (RC) should receive perioperative chemotherapy (CHT). However, the adherence to CHT guidelines is low. Thus, we tested contemporary CHT use rates and associated cancer-specific mortality (CSM) and overall mortality (OM) rates.Materials and methodsWithin the SEER database (2004–2015), we identified pT3N0/+ MIBC patients, who underwent RC, with or without perioperative CHT. Estimated annual percentage changes (EAPCs) analyses were used. After inverse probability of treatment weighting (IPTW), Kaplan–Meier (KM) analyses and Cox regression models (CRMs) tested the association of CHT on survival in the overall population (n = 3817), as well as after stratification according to stage, gender and age. Landmark analyses tested for immortal time bias.ResultsOverall, 44.3% of patients received CHT. Between 2004 and 2015, CHT administration rates increased from 32.1% to 55.6% (EAPC: +6.0%; p < 0.001). In CRMs, CHT was associated with lower CSM (HR 0.73, CI 0.65–0.81) and OM (HR 0.69, CI 0.62–0.76). In sensitivity analyses, CHT was also associated with lower CSM and OM in N0 patients (CSM: HR 0.76, 95% CI 0.65–0.88; OM: HR 0.69, 95% CI 0.60–0.79) and in N+ patients (CSM: HR 0.69, 95% CI 0.59–0.80; OM: HR 0.67, 95% CI 0.58–0.77), as well as according to gender and age. Landmark analyses confirmed the above results.ConclusionsPerioperative CHT was associated with better survival and its rate of use increased in locally-advanced MIBC RC patients. The latter confirm one large observational study and several small prospective studies.     

Histological Variants of Urothelial Carcinoma Predict No Response to Neoadjuvant Chemotherapy

BackgroundPlatinum-based neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIBC) has been adopted as a standard of care related to better survival outcomes. However, there is a considerable number of patients who do not respond, experiencing toxicity and delay in the surgical treatment. Our aim is to find biomarkers of response that could be easily adopted in the clinical practice.MethodsBetween January 2009 and July 2016, 52 patients with MIBC were submitted to radical cystectomy after NAC. A tissue microarray containing 25 cases, who met the inclusion criteria was built for immunohistochemical analysis of Cytokeratins 5/6, 7, and 20, GATA3, Her2, EGFR, p63, p53, Carbonic-anhydrase IX (CAIX), MLH1, MSH2, MSH6, and PMS2. The surgery was performed in a mean time of 58.7 (± 21) days after the end of the NAC. Fisher's exact test was used to analyze the relationship between response (≤pT1) and histopathological and immunohistochemical results and Kaplan–Meier curves were designed for survival analysis.ResultsTen (40.0%) patients presented response to NAC. Histological variants of the urothelial carcinoma characterized by squamous, sarcomatous/rhabdoid, plasmacytoid, and micropapillary was present in 36.0% and none responded to NAC (P = .002). CAIX was expressed by 53.3% and none responded to NAC (P= .005). Lymph-node metastasis, divergent differentiation, and expression of cytokeratin 5/6 were related to short cancer specific survival.ConclusionHistological variants and CAIX immune-expression are biomarkers of nonresponse to NAC of MIBC, and might be easily used in the clinical practice to select patients to be submitted to surgery upfront.     

Effect of internal iliac artery chemotherapy after transurethral resection of bladder tumor for muscle invasive bladder cancer

Objective： To evaluate the clinical effect of transurethral resection of bladder tumor（TUR-BT） combined with internal iliac artery chemotherapy and intravesical instillation therapy for muscle invasive bladder cancer（MIBC）.
Methods： From February 2007 to April 2014, 62 patients with MIBC were treated with TUR-BT combined with intravesical instillation therapy, with or without internal iliac artery chemotherapy, and the chemotherapy regimen is gemcitabine and cisplatin（GC）. The bladder preservation and survival rate as well as cancer-specific survival（CSS） rate and overall survival（OS） rate of the two groups were compared.
Results： Sixty-two patients were followed-up for 26-102 months with an average of 58.4±3.1 months. Recurrence-free survival（RFS） at 2-year for TUR ＋ GC group and TUR group were 77.8% and 53.8%, respectively. Bladder preserved rate（BPR） at 3-year for TUR ＋ GC group and TUR group were 94.4% and 80.8%. CSS rate at 2-year for TUR ＋ GC group and TUR group were 94.4% and 84.6%. The diseasefree survival（DFS） at 1-year for TUR ＋ GC group and TUR group were 83.3% and 61.5%, and 77.8% and 53.8% for the 2nd year. OS at 2-year for TUR ＋ GC group and TUR group were 88.9% and 92.3%.
Conclusions： TUR-BT and intravesical instillation therapy combined with internal iliac artery chemotherapy for MIBC had a better outcome at RFS, BPR and DFS than the treatment without internal iliac artery chemotherapy, and no difference in OS and CSS.     

Role of Maximal Endoscopic Resection Before Cystectomy for Invasive Urothelial Bladder Cancer

Introduction/BackgroundThe aim of this study was to examine whether TUR of all visible endophytic tumors performed before RC, with or without NC, affects final pathologic staging.Patients and MethodsWe retrospectively reviewed data from patients with clinical T2-T4N0-1 urothelial carcinoma of the bladder who underwent RC at our institution between July 2005 and November 2011. Degree of TUR was derived from review of operative reports. We used multivariate logistic regression to assess the association of maximal TUR on pT0 status at time of RC.ResultsOf 165 eligible RC patients, 81 received NC. Reported TUR of all visible tumors was performed in 38% of patients who did not receive NC and 48% of NC patients (P = .19). Nine percent of patients who underwent maximal TUR and did not receive NC were pT0, whereas among NC patients, pT0 was seen in 39% and 19% of those with and without maximal TUR, respectively (P = .05). On multivariate analysis in all patients, maximal TUR was associated with a nonsignificant increased likelihood of pT0 status (odds ratio [OR], 2.03; 95% confidence interval [CI], 0.84-4.94), which was significant when we restricted the analysis to NC patients (OR, 3.17; 95% CI, 1.02-9.83).ConclusionMaximal TUR of all endophytic tumors before NC is associated with complete pathologic tumor response at RC. Candidates for NC before RC should undergo resection of all endophytic tumors when feasible. Larger series are warranted to see if maximal TUR leads to improved overall and disease-specific survival.     

History of Non–Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy

Purpose

To investigate whether a history of non–muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC.

Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non–Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508)

IntroductionAlthough chemoradiotherapy (CRT) is the standard of care for patients with unresectable stage III non–small-cell lung cancer (LA-NSCLC), most patients relapse. Tecemotide is a MUC1 antigen-specific cancer immunotherapy vaccine. Bevacizumab improves survival in advanced nonsquamous (NS)-NSCLC and has a role in immune modulation. This phase II trial tested the combination of tecemotide and bevacizumab following CRT in patients with LA-NSCLC.Patients and MethodsSubjects with stage III NS-NSCLC suitable for CRT received carboplatin/paclitaxel weekly + 66 Gy followed by 2 cycles of consolidation carboplatin/paclitaxel ≤ 4 weeks of completion of CRT (Step 1). Patients with partial response/stable disease after consolidation therapy were registered onto step 2, which was 6 weekly tecemotide injections followed by every 6 weekly injections and bevacizumab every 3 weeks for up to 34 doses. The primary endpoint was to determine the safety of this regimen.ResultsSeventy patients were enrolled; 68 patients (median age, 63 years; 56% male; 57% stage IIIA) initiated therapy, but only 39 patients completed CRT and consolidation therapy per protocol, primarily owing to disease progression or toxicity. Thirty-three patients (median age, 61 years; 58% male; 61% stage IIIA) were registered to step 2 (tecemotide + bevacizumab). The median number of step 2 cycles received was 11 (range, 2-25). Step 2 worst toxicity included grade 3, N = 9; grade 4, N = 1; and grade 5, N = 1. Grade 5 toxicity in step 2 was esophageal perforation attributed to bevacizumab. Among the treated and eligible patients (n = 32) who were treated on step 2, the median overall survival was 42.7 months (95% confidence interval, 21.7-63.3 months), and the median progression-free survival was 14.9 months (95% confidence interval, 11.0-20.9 months) from step 1 registration.ConclusionsThis cooperative group trial met its endpoint, demonstrating tolerability of bevacizumab + tecemotide after CRT and consolidation. In this selected group of patients, the median progression-free survival and overall survival are encouraging. Given that consolidation immunotherapy is now a standard of care following CRT in patients with LA-NSCLC, these results support a role for continued investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC.     

Chemoradiotherapy as a bladder-preservation approach for muscle-invasive bladder cancer: current status and perspectives

Radical cystectomy has been considered the gold standard for the treatment of muscle-invasive bladder cancer. However, because of disappointing results with radical surgery in terms of survival and decreased quality of life (QOL), bladder-preservation treatment has been introduced as an alternative to radical cystectomy. The primary purpose of the bladder-preservation approach has been to maximize overall cure rates, with the secondary purpose being to preserve the patients bladder. The modalities used to ensure successful bladder preservation include radical transurethral resection (TUR), concurrent cisplatin (CDDP)-based chemotherapy, and radiotherapy. In patients who achieve a complete response (CR) after trimodality therapy, 5-year survival rates of more than 50%, the same as those of radical cystectomy, can be achieved and 70% of this group will retain an intact functional bladder.In this article, bladder-preservation studies using chemoradiotherapy are reviewed.     

Modified 5-Item Frailty Index Score as Prognostic Marker After Radical Cystectomy in Bladder Cancer

IntroductionA modified 5-item frailty index was recently developed as a predictor of patient comorbidity-based mortality and morbidity. We evaluate the association between preoperative modified 5-item frailty index score and prognosis after radical cystectomy for bladder cancer.Patients and MethodsIn this multicenter retrospective study, we calculated modified 5-item frailty index scores of the 238 patients that underwent radical cystectomy for bladder cancer between March 2009, and March 2018. The patients were classified into high frailty index score (≥ 2) or low frailty index score (≤ 1) groups for comparison of overall and cancer-specific survival between them. To evaluate the prognostic impact of the preoperative frailty index, we also performed Cox proportional regression analyses for overall, and cancer-specific survival.ResultsOf 238 patients, 53 patients were classified into the high frailty index score group and 185 patients into the low frailty index score group. Overall, 70 patients died of bladder cancer (29%), and 21 patients died of other causes (9%). The patients with high frailty index score had significantly lower rate of overall survival than those with low frailty index score (P < .01). On the other hand, there was no significant difference in cancer-specific survival rate between the 2 groups (P = .07). Multivariable Cox proportional hazard analysis revealed that high modified 5-item frailty index score was independently associated with poor overall survival (P = .01), but not with poor cancer-specific survival (P = .15).ConclusionHigh preoperative modified 5-item frailty index score could be a significant independent predictor of poor prognosis after radical cystectomy in patients with bladder cancer.     

Radical cystectomy for pT1 urothelial carcinoma of bladder not amenable to TURBT: Long-term results

PurposeThis study sought to identify factors associated with survival of pT1 urothelial carcinoma of bladder (UCB) after radical cystectomy (RC).MethodsThis study consists of 114 pT1 UCB [primary 83, recurrent 31, none were amenable to transurethral resection (TUR)] treated by radical cystectomy. Survival analysis using Cox regression tests were performed to identify factors associated with survival of pT1 UCB after RC.ResultsPelvic lymph node (LN) status, age and lymphovascular invasion (LVI) are associated with survival of pT1 UCB after RC; recurrent pT1 UCB of high grade origin (HGO) tends to have poorer CSS than primary pT1 UCB or recurrent pT1 UCB of low grade origin (LGO) (5-year and 10-year CSS rates was 75% and 73% for primary cases; 77% and 77% for recurrent pT1 UCB of LGO; and 56% and 37% for recurrent pT1 UCB of HGO, p = 0.078).ConclusionsLN status, age and LVI were significantly associated with survival of pT1 UCB after RC. Recurrent pT1 UCB of HGO should be managed with radical cystectomy in a timely fashion given that these cases tend to have poorer CSS than primary pT1 UCB after RC, even if they did not progress to muscle-invasive bladder cancer (MIBC).     

Role of Neoadjuvant Chemotherapy in Squamous Variant Histology in Urothelial Bladder Cancer: Does Presence and Percentage Matter?

BackgroundThe purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT.Materials and MethodsThe records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (< 50% SV vs. ≥ 50% SV).ResultsThe median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P < .001). The non-organ–confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organ–confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival.ConclusionsThe effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has < 50% involvement by the variant histology.     

Sequential Targeted Therapy After Pazopanib Therapy in Patients With Metastatic Renal Cell Cancer: Efficacy and Toxicity

Introduction/BackgroundPatients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy.Patients and MethodsPatients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions. Pazopanib was given as first-line therapy in 28 patients and after cytokines therapy in 7 patients. Clinical outcome and toxicity analyses of 2 sequential treatment options (anti-vascular endothelial growth factor [VEGF] or mammalian target of rapamycin inhibitor [mTORi]) is presented.ResultsSubsequent therapy was anti-VEGF in 22 patients and mTORi in 13. One patient who received bevacizumab and temsirolimus combination was excluded. VEGF-targeted therapies included sorafenib (n = 10), sunitinib (n = 3), bevacizumab (n = 2), cediranib (n = 4) and cabozantinib (n = 3). Patients treated with mTORi received everolimus. Median progression-free survival was 5.6 months from the start of subsequent therapy with anti-VEGF and 2.4 months with mTORi (P = .009). Overall survival (OS) was not significantly different (P = .68). Clinical benefit (including partial response and stable disease) on subsequent therapy was observed in 15 patients (64%) and 4 patients (31%) of anti–VEGF- and everolimus-treated patients, respectively (P = .021).ConclusionIn this retrospective study, targeting VEGF was an effective strategy after disease progression during pazopanib treatment, although OS was not different among patients treated with VEGF or mTORi.     

Neoadjuvant Chemotherapy Before Bladder-Sparing Chemoradiotherapy in Patients With Nonmetastatic Muscle-Invasive Bladder Cancer

Background

Cisplatin-based neoadjuvant chemotherapy (NAC) before cystectomy improves survival in muscle-invasive urothelial bladder cancer (MIBC). The use of NAC before chemoradiation (CRT) has been limited, as these patients are often elderly, frail, and ineligible for cisplatin. However, the role of NAC in fit, cisplatin-eligible patients who opt for bladder preservation warrants further evaluation.

Assessment of Tolerability,Response and Complications of Concurrent Chemoradiation With Capecitabine and Cisplatin in Muscle-Invasive Bladder Cancer; A Single Arm Study

PurposeTo evaluate the feasibility, tolerance and efficacy of cisplatin+capecitabine as a proposed combination in concurrent chemoradiotherapy for patients with muscle-invasive bladder cancer (MIBC).MethodsMIBC patients with stage T2-T4aN0M0 participated in this single-arm clinical trial. After maximal TURBT, 66Gy/33 daily fractions of radiation were administered with concurrent chemotherapy of cisplatin (35 mg/m²) and capecitabine (625 mg/m²). The primary endpoint was treatment tolerability, defined as receiving capecitabine+cisplatin combination for at least 5 weeks during radiation therapy. The secondary endpoints included complete response (CR) and acute toxicity rates.ResultsThis study included 19 MIBC patients from 2018 to 2019. Eighteen patients (94.7%, 95%CI: 75.4-99.0) completed the planned treatment course. Only one patient (5.26%, 95%CI: 0.9-24.6) discontinued the treatment due to grade-3 GI toxicity. Among those who completed the treatment, CR was seen in 12 patients (66.7%, 95% CI = 44.4-88.9) with no grade ≥ 3 toxicities. The most common grade-2 side effects during therapy were renal complications (57.9%), and the only grade-2 complication after therapy was urinary-related (11.1%). The median follow-up was 31 months and the median overall survival (OS) was 31 months. The 2-year OS was 78% (95% CI 58.4-97.6), Cystectomy-free survival was 61% (95% CI: 37.5-84.5), and the median OS after recurrence was 13 months. Distant metastases were the first type of recurrence in most patients with a recurrence, which occurred in 7 (36.8%) patients. Median metastasis-free survival (MFS) was 30 months, and 2-year MFS was 66% (95% CI:45-87).ConclusionThe promising tolerability rate seen with concurrent cisplatin+capecitabine in this study was comparable to the available literature. Thus, this combination concurrently with radiation warrants further studies in the context of chemoradiotherapy of MIBC.