Tumor Marker May Help Choose Best Therapy for Metastatic Prostate Cancer

By Lorraine L Janeczko

March 20, 2016

NEW YORK (Reuters Health) - A tumor marker in peripheral blood may help determine which men with metastatic castration-resistant prostate cancer (mCRPC) respond well to docetaxel and which will benefit from a different therapy, researchers from Spain suggests.

"A specific genetic alteration, TMPRSS22-ERG rearrangement, detected in the blood of patients with mCRPC may indicate the presence of circulating tumor cells harboring this genetic alteration and predict taxane resistance," said Dr. Begona Mellado from the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) in Barcelona.

"Nearly 90% of patients with TMPRSS2-ERG in their blood do not respond to taxanes, standard chemotherapeutic agents in this disease," she told Reuters Health by email.

Dr. Mellado and her colleagues evaluated TMPRSS2-ERG expression using quantitative reverse transcription polymerase chain reaction in peripheral blood mononuclear cells and tumor tissue from mCRPC patients treated with taxanes.

The team examined cells from 24 healthy controls, 50 patients treated with docetaxel, and 22 treated with cabazitaxel. They detected TMPRSS2-ERG in 0%, 16%, and 22.7%, respectively, they report in European Urology, online March 1.

Docetaxel-treated patients who were positive for TMPRSS2-ERG had lower prostate-specific antigen (PSA) response rate than did those who were negative for the gene fusion (12.5% vs. 68.3%, p=0.005). They also had lower PSA-progression-free survival (PFS, 3.1 months vs. 7.5 months; p<0.001) and clinical/radiological-PFS (3.1 months vs. 8.2 months; p<0.001).

TMPRSS2-ERG detection was independently associated with PSA-PFS (hazard ratio, 3.7; p=0.009) and clinical/radiological-PFS (HR, 6.3; p<0.001). The gene fusion also predicted low PSA-PFS to cabazitaxel.

At progression, a switch from negative to positive TMPRSS2-ERG was found in 41% of patients with undetected TMPRSS2-ERG in the baseline sample; and tissue TMPRSS2-ERG expression correlated with lower PSA-PFS (p=0.02) to docetaxel.

"While this study was small, the differences in response between the two groups was striking based on PSA declines with chemotherapy, suggesting that this relatively simple blood test may be an indicator of which patients may respond better to docetaxel chemotherapy," said Dr. Andrew J. Armstrong, a prostate cancer expert at Duke University in Durham, North Carolina.

"If validated prospectively in larger studies," Dr. Armstrong told Reuters Health by email, "this blood test may enable physicians to select the right chemotherapy agent for the right patient with advanced prostate cancer."

Dr. David S. Rickman, a pathologist at Weill Cornell Medicine in New York City, observed, "As the frequency of TMPRSS2-ERG for these types of patients can reach over 50%, and taxanes are the most commonly given chemotherapeutic agent, these results have the potential to impact a significant number of men with mCRPC."

"It would have been helpful if the authors had provided more details on the sensitivity and specificity of the TMPRSS2-ERG Taqman assay used to query the peripheral blood mononuclear cells," he told Reuters Health by email. "This assay would need to be validated by an independent group."

Dr. Donald Vander Griend, director of urological research at the University of Chicago, said the "findings are somewhat surprising, since one would not expect a general prostate tumor marker, TRMPRSS2-ERG translocation, to delineate between two different responses and be associated with poor response to therapy."

"Testing for TMPRSS2-ERG translocations in blood can be done routinely," Dr. Griend said in an email to Reuters Health. "Determining which patients would have the greatest benefit to taxane therapy using simple blood-based assays can help with disease management."

"The biggest question is whether this observation holds up when tested in a larger and more diverse patient population," he added.

Dr. Mellado's group is currently conducting a prospective study that includes more patients in multiple centers in Spain. "If confirmed, the detection of TMPRSS22-ERG in blood would be useful to identify patients who are refractory to taxane-based chemotherapy, to spare them from unneccessary toxicity, and to investigate new therapeutic approaches," she said.

SOURCE: bit.ly/1RkVYjk

Eur Urol 2016.