Washington, DC USA (UroToday.com) In today’s general session at the 2015 Society of Urologic Oncology, Dr. Eric Small presented his work on intermediate atypical prostate cancer (CaP), a relatively new form of castrate-resistant prostate cancer (CRPC).
Clinically, we’ve observed that abiraterone (Abi) and enzalutamide (Enza) prolong life, yet despite initial success with these agents, CRPC continues to progress. Dr. Small and his group aimed to identify and target adaptive pathways in metastatic abiraterone acetate and enzalutimide resistant prostate cancer. With a 6-center consortium, the group biopsied CRPC after novel AR-targeted treatment followed by regular clinical assessment along with serum, plasma and blood draws for circulating tumor cells. An optional biopsy was performed at progression. 220 biopsies were performed as of this month, with the vast majority being from bone. The remainder were from lymph nodes, liver, lung, adrenal, soft tissue, brain, and bladder. The protocol had an overall success rate of 78%, with the lowest success rate in bone (65%). Following biopsy, the tissue was split and then evaluated both by FFPE as well as laser capture mirodissection for genomic analysis.
The investigators found that 38% of 158 evaluable biopsies were pure adenocarcinoma, 11% were small cell neuroendocrine tumors (possibly because these patients are heavily pre-treated), and 29% were a new entity labeled “intermediate atypical carcinoma” (IAC)—histologically distinct from both small cell and adenocarcinoma. The group found that histologically, IAC possesses unique and reproducible microscopic features, including moderate to abundant cytoplasm, fine homogeneous chromatin, dark nuclear staining, absent or small nucleoli, vague glandular formation, and rare mitotic figures. Beyond being histologically distinct, the phenotype produces a clinically meaningful survival difference compared to adenocarcinoma (25.8 months for adeno, 19.1 months for IAC). Survival curves are even more divergent when comparing adeno vs “not adeno” (ie small cell + IAC). Multivariate modeling demonstrated that histologic subtype was an independent predictor for survival. As for metastases, there is no clear pattern to the sites of disease, as IAC is found in all tissue.
It is important to avoid the presumption that liver harbors aggressive variants (1/3 are pure adeno) and that lymph node generally harbors less aggressive variants (more commonly have non-adeno). Genetic studies are currently underway as a 50 gene- and full gene set signature has been identified.
Dr. Eric J. Small
UCSF Comprehensive Cancer Center
Dr. Nikhil Waingankar, MD* from the 2015 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" December 2 - 4 Washington, DC USA
*Fox Chase Cancer Center, Philadelphia, PA USA