Basic Science Research: Trimodal therapy shows promise in oligometastatic PCa

Trinity J. Bivalacqua, MD, PhDOther basic science research pearls include preliminary evidence from a porcine model suggesting botulinum toxin type A facilitates ureteral stone passage and the identification of two different microdeletions in the NELL1 gene on chromosome 11 in men with Peyronie's disease. The basic science research take-home messages were presented by Trinity J. Bivalacqua, MD, PhD, of Johns Hopkins University, Baltimore.

Trimodal therapy with neoadjuvant degarelix (Firmagon), cryoablation, and anti-PD-1 therapy extends survival and causes a distant tumor immune response in an immune competent model. Early treatment results from a trial in three men with hormone-naïve oligometastatic prostate cancer are promising.

In an evaluation of BPH samples, elevated aromatase and phosphorylated estrogen receptor levels in patients lacking 5-alpha steroid reductase 2 (SRD5A2) expression suggests an androgenic-to-estrogenic switch in growth signaling. Therefore, targeting the aromatase-estrogen axis may serve as an effective treatment strategy in patients who lack SRD5A2 expression.

Two different microdeletions in the NELL1 gene on chromosome 11 were identified in two of 19 men with Peyronie’s disease, as well as a microdeletion in one man corresponding to part of the CTDSPL gene, both of which are associated with fibrosis. NELL1 overexpression was found to downregulate profibrotic cytokines and upregulate antifibrotic cytokines in tunica albuginea fibroblasts, producing myofibroblasts that increase fibrosis in Peyronie’s disease. 

Preliminary evidence suggests that periureteral botulinum toxin type A injection facilitates ureteral stone passage in a porcine model.

Stromal derived factor (SDF)-1 is a small, highly conserved chemokine that binds to CXCR4 and CXCR7. As a potent stem cell chemo-attractant, it may have anti-apoptotic, angiogenic, and neurogenic properties.

• SDF-1 injection accelerates recovery of continence in a rat model of vaginal distention injury.

• SDF-1 treatment prevents erectile dysfunction and enhances nerve regeneration via CXCR4 activation of neurotrophic factors in an RP injury model. Mice with implanted PC3 that received SDF-1 penile injections did not have increased cancer burden or metastases compared with saline-injected mice.

• Genomic concordance rates of matched-pair renal cell carcinoma samples provide evidence for clonal evolution. Discordance between matched pairs in driver mutations were found in PTEN, TP53, NF2, FGFR1, and MET. The presence of discordance actionable mutations provides further reason to biopsy and sequence metastatic disease.

• Expression profiling in human urothelial bladder cancer identifies luminal and basal-like molecular subtypes of disease; however, many cell lines do not have a clear subtype. Cell lines that most closely represent human tumors are RT4, UMUCI, and SCABER; these cell lines are suitable models for the study of the relationship between molecular subtype and disease pathogenesis.

• Next-generation sequencing of cell-free DNA reveals genomic aberrations in metastatic urothelial carcinoma, which may be used to monitor and predict treatment response.

More from AUA 2016:

Sexual Function/Dysfunction: Mixed results with CCH in Peyronie's

Trauma/Reconstruction/Diversion: New clinical guidelines for stricture

Female Urology: Improvements in OAB therapy

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