Munich, Germany (UroToday.com) Dr. Bedke presented on the management of atypical prostate cancer histology. Currently, there are no guidelines present in management of these atypical subtypes. EAU guidelines are not explicit how to manage these patients but state that atypical subtypes should be excluded from active surveillance when a needle biopsy is diagnostic for these.
There are several types of primary atypical histology. Even for primary prostatic neuroendocrine tumors, there are 5 subtypes (adenocarcinoma with neuroendocrine differentiation, adenocarcinoma with paneth cell-like neuroendocrine differentiation, Well-differentiated neuroendocrine tumor, small cell neuroendocrine caricinoma, and large cell neuroendocrine carcinoma). These subtypes are PSA negative on immunohistochemistry but can be positive or negative for neuroendocrine markers. Pure neuroendocrine prostate cancer are rare consisting of 2% of primary prostate tumors. The median survival is low and estimated to be about 10 months.
Neuroendocrine malignancy is thought to arise from either basal progenitor cells, adenocarcinoma cells, or benign neuroendocrine/luminal cells. These can happen in the setting of associated molecular changes (TMPRSS2-ERG fusions, AR amplication, AURKA amplication, RB1 loss). These can arise from either from transdifferentiation from adenocarcinoma or by clonal selection of neuroendocrine cells.
Intermediate Atypical Carcinoma (IAC) is a new entity CRPC described which are characterized to be resistant to Abiraterone or Enzalutamide. They have poor survival compared to adenocarcinoma. They can have predominant visceral or lytic bone metastasis. Response to ADT may be < 6 months. PSA may be negative and they can express some neuroendocrine markers.
Chemotherapy regimens for atypical prostate carcinoma are poorly studied. Both cabazitaxel and docetaxel were studied in patients with adenocarcinoma and not with atypical histologies. However, recent phase II study on chemotherapy use platinum based therapies (Aparicio AM et al, Clin Cancer Res 2013). Phase II trials targeting molecular changes are accruing. For example, phase II trial using a Auroral Kinase A inhibitor is underway (NCT01799278). Recently, a trial of PARP inhibitor Olaparib in mCRPC patients was reported (Mateo J et al, NEJM 2015). These may lead to personalized approaches as genomic types are first characterized prior to administration of treatment.
In conclusion, management recommendations of neuroendocrine prostate cancer are not clear. If confined to the prostate, surgical treatment or radiotherapy is the first option. Chemotherapy or genomic target agents are required for metastatic atypical prostate cancer and personalized approaches are being developed.
Presented By:
J.P. Bedke, Tübingen (DE))
Reported By:
Mohammed Haseebuddin, MD, at the 31st Annual EAU Congress - March 12 - 15, 2016 – Munich, Germany
Fox Chase Cancer Center