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We are now using PARP inhibitors for DNA repair-deficient patients with breast, ovarian, fallopian tube or primary peritoneal cancer.  In the realm of genitourinary oncology, we are meticulously exploring PARP inhibition, particularly for enriched patient populations with prostate cancer.  This is due to the fact that DNA repair deficiency occurs in approximately 23% of men with metastatic castration-resistant prostate cancer,1 and approximately 12% of men with metastatic prostate cancer harbor germline alterations.2
The title of this article is admittedly ironic and amusing. It goes back to the term “watchful waiting” of low and very low-risk prostate cancer. Although we were waiting for either something bad to happen or more often nothing exciting to happen due to indolent prostate cancer, the term “watchful” may have been a misnomer, as it is unclear if or how patients were being watched. The modern term of “active surveillance” is probably a more accurate term. It implies that patients are indeed, being surveyed by some accepted “active” script, usually with PSA testing and intermittent prostate needle biopsies. What that script looks like differs based on national
Antibody drug conjugates (ADCs) are a promising method of selective intensification of therapy, offering increased drug concentration to the target with minimal collateral damage to healthy tissue.1   Structurally, ADCs are monoclonal antibodies specific for a tumor antigen connected by a linker molecule to a cytotoxic drug payload.  After endocytotic internalization of the complex, the linker is degraded in a lysosome, releasing the cytotoxic payload.  There are now many FDA approved ADCs, including brentuximab vedotin for anaplastic2 and refractory Hodgkin lymphomas,3 trastuzumab emtansine
One year ago, in this column, I highlighted the non-metastatic (M0) castration-resistant prostate cancer (CRPC) disease state as a fruitful area for clinical trial exploration.1  As part of that article, I emphasized the concept of testing low toxicity, high efficacy agents from metastatic CRPC in earlier disease states.  Two of the randomized, phase 3 trials have just came out and the results are quite impressive.
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 

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