The Role of Salvage Radical Prostatectomy in Patients with Radiation-Resistant Prostate Cancer

There are multiple treatment strategies for patients with localized prostate adenocarcinoma. In intermediate- and high-risk patients, external beam radiation therapy demonstrates effective long-term cancer control rates comparable to radical prostatectomy. In patients who opt for initial radiotherapy but have a local recurrence of their cancer, there is no unanimity on the optimal salvage approach. The lack of randomized trials comparing surgery to other local salvage therapy or observation makes it difficult to ascertain the ideal management. A narrative review of existing prospective and retrospective data related to salvage radical prostatectomy after radiation therapy was undertaken. Based on retrospective and prospective data, post-radiation salvage radical prostatectomy confers oncologic benefits, with overall survival ranging from 84 to 95% at 5 years and from 52 to 77% at 10 years. Functional morbidity after salvage prostatectomy remains high, with rates of post-surgical incontinence and erectile dysfunction ranging from 21 to 93% and 28 to 100%, respectively. Factors associated with poor outcomes after post-radiation salvage prostatectomy include preoperative PSA, the Gleason score, post-prostatectomy staging, and nodal involvement. Salvage radical prostatectomy represents an effective treatment option for patients with biochemical recurrence after radiotherapy, although careful patient selection is important to optimize oncologic and functional outcomes

Sexual function and fertility preservation in testicular cancer survivors

Testicular cancer is a common cancer among reproductive age men, with the necessary treatment options having varying impacts on fertility and sexual function. Treatment begins with orchiectomy and is often followed by a combination of chemotherapy, radiation, and/or retroperitoneal lymph node dissection, which have different effects on spermatogenesis, gonadotropin levels, and ejaculation. Alkylating agents such as cisplatin are commonly used for testicular cancer and are amongst the most spermatotoxic chemotherapeutic agents. Radiation poses gonadotoxic effects despite gonadal shielding due to a scatter effect. Suprahilar and bilateral retroperitoneal lymph node dissections can cause ejaculatory dysfunction. Options to preserve fertility vary by pubertal status. While the standard recommendation for post pubertal patients is cryopreservation, prepubertal patients rely on experimental protocols for cryopreservation of germ cells with stem cell capabilities, with the hope that these cells will one day be stimulated to produce sperm. These topics are reviewed to give insight into current literature around fertility in testicular cancer survivorship and determine best possible practices in fertility preservation among patients

Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma

Abstract Intra-tumor heterogeneity contributes to treatment failure and poor survival in urothelial bladder carcinoma (UBC). Analyzing transcriptome from a UBC cohort, we report that intra-tumor transcriptomic heterogeneity indicates co-existence of tumor cells in epithelial and mesenchymal-like transcriptional states and bi-directional transition between them occurs within and between tumor subclones. We model spontaneous and reversible transition between these partially heritable states in cell lines and characterize their population dynamics. SMAD3, KLF4 and PPARG emerge as key regulatory markers of the transcriptional dynamics. Nutrient limitation, as in the core of large tumors, and radiation treatment perturb the dynamics, initially selecting for a transiently resistant phenotype and then reconstituting heterogeneity and growth potential, driving adaptive evolution. Dominance of transcriptional states with low PPARG expression indicates an aggressive phenotype in UBC patients. We propose that phenotypic plasticity and dynamic, non-genetic intra-tumor heterogeneity modulate both the trajectory of disease progression and adaptive treatment response in UBC

Does Time to Adjuvant Chemotherapy after Radical Cystectomy Affect Survival in Muscle Invasive Bladder Cancer? A Systematic Review

(1) Purpose: To assess the survival benefit for different times to adjuvant chemotherapy after a radical cystectomy. (2) Materials and Methods: We systematically searched PubMed®, Cochrane Central®, Scopus®, and Web of Science® library databases for original articles that looked at timing to adjuvant chemotherapy after radical cystectomy. Primary endpoints were five-year survival, progression free survival, and overall survival. Available multivariable hazard ratios and corresponding 95% CIs were included in the qualitative analysis. The risk of bias was completed for nonrandomized studies. (3) Results: Using PRISMA guidelines, our electronic search resulted in a total of 1862 records. After a detailed review, we selected four studies that addressed the impact of the timing of adjuvant chemotherapy for patients who underwent radical cystectomy. (4) Conclusion: A survival benefit was seen with an earlier administration of adjuvant chemotherapy, albeit a benefit persists for delayed chemotherapy post-radical cystectomy. A safe and ethical approach at this time would be to administer adjuvant chemotherapy as early in the postoperative period as possible, given the known survival benefit of such therapy (9–11% absolute survival benefit at five years)