Washington, DC (UroToday.com) Dr. Ana Aparicio from MD Anderson defined aggressive-variant prostate carcinomas (AVPS) as those carcinomas with behavior similar to small cell prostate cancer (SCPC) but morphologically different on histology.
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Clinicopathological features of AVPS include small-cell prostate carcinoma on histology (pure or mixed), exclusive visceral metastasis, predominantly lytic bone metastasis, bulky prostate/pelvic mass/lymphadenopathy, low PSA relative to tumor burden, abnormal neuroendocrine markers, and short response to ADT. Patients with AVPS respond to platinum –based chemotherapy similar to SCPC. A double-arm study between Cabazitaxel and cabazitaxel + carboplatin illustrated that men with AVPS are benefitted by the addition of platinum-based chemotherapy.
Dr. Aparicio’s group investigated whether AVPS patients shared molecular features in addition to clinical features even though histologically heterogeneous. They have found that AVPS patients are frequently RB negative, PTEN negative, and p53 mutated. RB-loss is associated with mutant p53, loss of androgen-receptor, and high KI67. RB loss and PTEN loss are common but there is a weak correlation between expression by immunohistochemistry and copy number. The group has proposed a candidate molecular signature for AVPS, which include combined alteration in RB, p53 and PTEN. Loss of each gene does not produce a lethal cancer, but when combination results in aggressive and metastatic disease.
The group is planning on investigating the link between AVPC to AR resistance (DynaMO trial), DNA damage repair pathways (PARP inhibition pathway), and control of primary tumor via surgery or radiation despite metastatic disease. The group concludes that AVPC are biologically distinct subset of prostate cancers that share the molecular and therapeutic phenotype of small cell prostate cancer. A combined defects in p53, RB and PTEN characterize and replaces the morphology in the identification of AVPC.
Ana Aparicio, MD
MD Anderson Cancer Center
Mohammed Haseebuddin, MD medical writer for UroToday.com, from the 2015 Society of Urologic Oncology (SUO) Meeting "Defining Excellence in Urologic Oncology" - December 2 - 4 2015 - Washington, DC USA