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Immune checkpoint inhibitors (e.g. anti-PD1/PDL1, anti-CTLA4) have revolutionized the treatment of multiple tumor types, including urothelial and renal cell carcinomas.1, 2 Unfortunately, response rates to anti-PD1/PDL1 therapy are still generally low, although those who do respond or who have stable disease may have long-term durable clinical benefit.  It is likely that combination immunotherapy strategies targeting multiple negative regulators of tumor immune responses will be more effective than anti-PD1/PDL1 monotherapy.
PD-1/PD-L1 antibodies are being studied in every disease state imaginable for patients with urothelial carcinoma.  Atezolizumab, nivolumab, durvalumab and avelumab are all regulatory approved for patients with metastatic disease in the post-platinum chemotherapy setting.1-4  Pembrolizumab is also approved and is the only agent to have demonstrated an overall survival benefit to date when compared to taxane chemotherapy in the post-platinum setting.5  Additionally, atezolizumab and pembrolizumab are approved for patients who are ineligible for cisplatin chemotherapy in the 1st-line. 6,7 
The fibroblast growth factor receptor (FGFR) family has functional roles in regulation of cell proliferation, differentiation, migration, angiogenesis and tumorigenesis.  Activating point mutations of FGFR3 are common (~86%) in low grade and stage bladder tumors.1  However, The Cancer Genome Atlas Research Network identified only 12% of muscle invasive bladder cancers with FGFR3 mutations.2  FGFR3 mutations are also very common in upper tract urothelial tumors, especially of the ureter.3  FGFR1 has been less intensively studied, but increased expression at both the mRNA and protein level is present in a large proportion of bladder tumors.4 
Radium-223 is actually quite capable of dancing on its own without a partner.  It offers an overall survival, symptomatic skeletal events and multiple pain and quality of life benefits for patients with bone metastatic castration-resistant prostate cancer and symptoms.1  Yet, the ALSYMPCA trial, which established the beneficial effects of radium-223, did not mandate regular imaging, so image surveillance expectations are uncertain.  Additionally, prostate-specific antigen (PSA) level does not always associate with clinical outcomes with Radium-223.  Given the mechanism of action of Radium-223, as an alpha-particle emitting radiopharmaceutical that incorporates into areas of osteoblastic activity, it is not surprising that alkaline phosphatase serves as not only a good baseline prognostic marker2 but also a good treatment response biomarker.3
Neoadjuvant chemotherapy use has been on the rise in the last 15 years for patients with high-risk localized urothelial carcinoma.  This is obviously due to randomized control data supporting an overall survival benefit.1,2  However, it has taken significant time for the field to embrace and adopt widespread use of cisplatin-based combination chemotherapy regimens in this setting.  Early reports showed neoadjuvant chemotherapy utilization rates to be 7.6% in 2006, 3 years after the original randomized control trial was published supporting the use of methotrexate, vinblastine, adriamcyin and cisplatin.3 
It is fortunate that we cure the vast majority of men with testicular germ cell tumors.  Estimates show that only approximately 10% of men with metastatic Stage III germ cell tumors are not cured.1  The bad news if that for those who aren’t cured with standard dose combination cisplatin-based chemotherapy with or without eventual high dose chemotherapy with autologous stem cell rescue (stem cell transplant), there are few options.  Palliative chemotherapy is often limited in efficacy, and regimens such as gemcitabine with oxaliplatin have been used.2  
Early attempts at checkpoint inhibition in prostate cancer seemed to offer little promise.  The initial trial with CTLA-4 inhibition with ipilumumab was performed in patients with metastatic castration-resistant prostate cancer (mCRPC) in the post-docetaxel setting and resulted in a HR 0.85, 95% CI 0.72-1.00; p=0.053.1 

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