Introduction: Collecting duct carcinoma (CDC) is a rare, aggressive form of renal carcinoma that presents at an advanced stage and has a poor prognosis. Little is known concerning the optimal management of CDC. We present the results of a systematic review addressing the management of CDC and the McMaster University CDC series. Methods: The MEDLINE, Cochrane Library, and EMBASE databases and conference proceedings were searched to identify studies relating to the management of CDC. Included studies reported on a minimum of 10 subjects receiving a single intervention. Series in which an evaluation of therapeutic effectiveness was not possible were excluded. The McMaster University (Hamilton, Ontario) series of 6 cases of CDC were retrospectively reviewed. Results: We identified 3 studies relevant to the management of CDC that included a total of 72 patients. A gemcitabine–cisplatin or –carboplatin regimen resulted in a 26% objective response rate in 23 patients with metastatic CDC. Two additional studies indicated that 49 patients treated with immunotherapy achieved no response. In the McMaster series, cytoreductive nephrectomy was performed in 4 of 6 patients. In 2 patients, MVAC therapy (methotrexate–vinblastine–doxorubicin–cisplatin) achieved no response. No significant therapeutic complications occurred, but survival was poor (median: 11 months; range: 10–33 months). Conclusions: Our review and clinical experience suggest that the current standard of care for metastatic CDC is a gemcitabine–cisplatin regimen.
Background: We seek to determine if testosterone levels below the accepted castration threshold (50 ng/dL) have an impact on time to progression to castrate-resistant prostate cancer (CRPC). Methods: This is a prospective cohort series of patients undergoing androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone agonist or antagonist at a tertiary centre from 2006 to 2011. Serum testosterone level was assessed every 3 months. Patients with any testosterone >50 ng/dL were excluded. Patients were stratified into groups based on those achieving mean testosterone levels <20 ng/dL and <32 ng/dL. Progression to CRPC was assessed with the Kaplan-Meier method and compared with the log-rank test. Results: A total of 32 patients were included in this study. Mean patient follow-up was 25.7 months. Patients with a 9-month serum testosterone <32 ng/dL had a significantly increased time to CRPC compared to patients with testosterone 32 to 50 ng/dL (p = 0.001, median progression-free survival (PFS) 33.1 months [<32 ng/dL] vs. 12.5 months [>32 ng/dL]). Patients with first year mean testosterone <32 ng/dL also had a significantly increased time to CRPC compared to 32 to 50 ng/dL (p = 0.05, median PFS 33.1 months [<32 ng/dL] vs. 12.5 months [32-50 ng/dL]). A testosterone <20 ng/ dL compared to 20 to 50 ng/dL did not significantly predict with time to CRPC. Conclusion: This study supports a lower testosterone threshold to define optimal medical castration (T <32 ng/dL) than the previously accepted standard of 50 ng/dL. Testosterone levels during ADT serve as an early predictor of disease progression and thus should be measured in conjunction with prostate-specific antigen.
Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of diseasespecific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.