Non-muscle invasive bladder cancer (NMIBC) represents the vast majority of bladder cancer diagnoses, however this definition represents a spectrum of disease with a variable clinical course notable for significant risk of recurrence and potential for progression. Management involves risk-adapted strategies of cystoscopic surveillance and intravesical therapy with a goal of bladder preservation when safe to do so. Multiple organizational guidelines exist to help practitioners manage this complicated disease process, however adherence to management principles amongt practicing urologists is reportedly low. We review four major organizational guidelines on NMIBC: American Urological Association (AUA)/Society of Urologic Oncology (SUO), European Association of Urology (EAU), National Comprehensive Cancer Network (NCCN), and National Institute for Health and Care Excellence (NICE).
Recently, the combination of androgen deprivation therapy (ADT) and radiation therapy (RT) has been shown to block the androgen receptor (AR)-driven DNA damage response (DDR) and enhance RT-mediated cell kill of prostate cancer (PCa). Since ADT may induce expression of AR splice variants (ARVs) we hypothesized that ARVs can drive DDR and mediate resistance to combined ADT and RT. Herein, we demonstrate that ARVs can increase the clonogenic survival of PCa cells following RT in an ADT-independent manner. RT induces the interaction between ARVs and a DDR driver, the DNA-dependent protein kinase catalytic subunit (DNA-PKc). Pharmacological inhibition of DNA-PKc blocks its interaction with ARVs and results in persistence of DNA damage, increased tumor cell kill and improved PCa cell survival following RT. These results indicate that combinatorial targeting of DNA-PKc with ADT and RT may be an effective strategy for overcoming radioresistance when treating clinically localized PCa.
PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.
Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling.
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