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Detecting genomic alterations (GAs) in advanced urothelial carcinoma (aUC) can expand treatment options by identifying candidates for targeted therapies. Erdafitinib is FDA-approved for patients with platinum-refractory aUC with activating mutation or fusion in FGFR2/3. We explored the prevalence and spectrum of FGFR2/3 GAs identified with plasma cfDNA NGS testing (Guardant360) in 997 patients with aUC. FGFR2/3 GAs were detected in 201 patients (20%) with characterized activating GAs in 141 (14%). Our results indicate the Guardant360-based FGFR2/3 GA detection rate is similar to those described from previous studies employing tumor tissue testing, suggesting that plasma-based cfDNA NGS may non-invasively identify candidates for anti-FGFR targeted therapies.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) has shown overall survival benefit for patients with muscle invasive bladder cancer (MIBC). In contrast, there is limited data for adjuvant treatment options in patients with residual muscle invasive disease after NAC followed by radical cystectomy (RC). OBJECTIVE: This systematic review aims to give an overview of studies examining adjuvant treatment options for patients with residual MIBC at RC despite NAC. METHODS: We systematically searched the PubMed database and Clinicaltrials.gov (end point August 2019) for publications and registered trials combining NAC, RC, and adjuvant treatment options. RESULTS: After removal of duplicates, 659 articles and registered trials were further analyzed. Finally, 10 studies and 7 registered clinical trials met inclusion criteria. While 5 publications did not further characterize NAC and adjuvant regimens, the remaining 5 studies reported mainly platinum-based regimens. Altogether, the selected studies showed conflicting results regarding the potential role of adjuvant treatment strategies in the setting of residual disease after NAC and RC. CONCLUSION: Although there is an urgent need for adjuvant treatment options for patients with MIBC after NAC and residual muscle invasive disease at RC, there has been very limited evidence available. Inclusion of such patients into ongoing adjuvant clinical trials is urgently needed; active surveillance is strongly recommended in the absence of trials.

Bladder cancer is a heterogeneous disease including conventional urothelial carcinoma (UC) and its histologic variants, and non-urothelial carcinoma, including squamous and glandular neoplasms. Urothelial carcinoma accounts for the majority of bladder cancer cases, but morphologic variants are common and include nested, microcystic, micropapillary, lymphoepithelioma-like, plasmacytoid, sarcomatoid, giant cell, undifferentiated, clear cell and lipoid. Certain variants of UC tend to be associated with a poor prognosis and have diagnostic and potential treatment implications that make the identification of variant histology crucial to clinical decision making. While there is still uncertainty regarding the prognostic implications of many of these variants, identifying and reporting variant histology is important to develop our understanding of their biology. Unique molecular features accompany many of these morphologic variants and to better understand these tumors, we review the molecular and clinical implications of histologic variants of bladder cancer. Major efforts are underway to include variant histology and divergent differentiation of UC in clinical trials to develop evidence based approaches to treatment. The purpose of this article is to review the current literature on variant histology of urothelial cancer and to highlight molecular findings and the clinical relevance of these tumors.

BACKGROUND: Plasmacytoid urothelial carcinoma is a rare bladder cancer variant with scarce data on outcomes and prognostic factors. OBJECTIVE: We report our institutional experience with this histology to determine response to neoadjuvant chemotherapy, definitive surgery and survival. METHODS: We conducted a retrospective chart review of consecutive patients with plasmacytoid, as well as conventional urothelial carcinoma (for comparison) seen in our institution (2007– 2018). Baseline characteristics, clinicopathologic and treatment data were captured. T-test, chi-squared and log-rank test was used for group comparison. Kaplan Meier method was used for estimation of overall survival and Cox regression for identification of prognostic factors. RESULTS: 64 patients with plasmacytoid and 418 with conventional urothelial histology were identified; 53% of those with plasmacytoid presented with cT3/4 stage and 67% underwent extirpative surgery. Patients with plasmacytoid histology had higher rates of pT3/4 (65% vs. 28%), nodal disease (37% vs. 16%) and positive surgical margins (23% vs. 5%) compared to urothelial group (p

Objective: Sarcopenia, or the age-related loss of skeletal muscle mass and function, has been investigated as a potential marker of adverse outcomes among surgical patients. Our aim was to assess for changes in psoas muscle volume (PMV) following administration of neoadjuvant chemotherapy (NAC) in patients with bladder cancer and to examine whether changes in PMV following NAC are predictive of perioperative complications, pathologic response or survival. Methods: During the period of 2009–2013, patients undergoing NAC and radical cystectomy (RC) at our institution with pre and post NAC cross sectional images available were included. Bilateral total psoas muscle volume (PMV) was obtained from pre- and post- NAC images and the proportion of PMV change was calculated by dividing the change PMV by pre-NAC PMV. Analyses for the assessment of factors predicting PMV loss, partial/complete pathologic response (pPR/pCR), complications, readmission, cancer specific (CSS), recurrence-free (RFS) and overall survival (OS) were performed. Results: Total of 60 patients had complete radiological data available. Post-NAC PMV and BMI declines were statistically significant, 4.9% and 0.05%, respectively. NAC dose reduction/delay was a significant predictor of PMV loss (coefficient B 4.6; 95% CI 0.05–9.2; p = 0.047). The proportion of PMV decline during NAC was not a predictor of pPR, pCR, complications, readmission, CSS, RFS, or OS. Conclusions: We observed an interval decline in PMV during the period of NAC administration and this decline was more than it could be appreciated with changes in BMI during the same period. PMV decline was associated with the need for dose reduction/dose delay during NAC. In our series, PMV changes occurring during NAC administration were not predictive of pathologic response to chemotherapy, postoperative complications or survival.