Predictive biomarkers for personalized medicine in advanced prostate cancer

Pearl Toh
01 Aug 2016

Understanding biomarkers predictive of treatment outcomes or response can help inform treatment decisions and personalize care for advanced prostate cancer patients, suggested an expert at the recent Urological Association of Asia Annual Congress (UAA 2016) held in Singapore.

Prostate cancer is a heterogeneous disease, with a wide variability in terms of treatment outcome and response between patients as well as within patients, said Dr. Fred Saad, chairman of Urology and director of G-U Oncology at the University of Montreal Hospital Centers (CHUM), Montreal, Canada, warranting the need for predictive biomarkers to differentiate the type of prostate cancer that would respond to a certain treatment.

“Many of the biomarkers are prognostic, although what we really need is predictive and surrogate biomarkers that help us in our decision making,” said Saad.

In patients with metastatic hormone-sensitive prostate cancer, combining docetaxel chemotherapy with androgen deprivation therapy (ADT) which was considered the standard of care and known to significantly improve overall survival (OS) (hazard ratio [HR] for death, 0.60; p=0.0006), [J Clin Oncol 2014;32:abstract LBA2] seemed to benefit patients with a higher tumour volume than those with a lower tumour volume, according to the latest results from the CHAARTED study, said Saad.

In fact, the updated data showed that adding docetaxel chemotherapy to ADT might not benefit metastatic hormone-sensitive prostate cancer patients with a low-volume disease at all, yielding a HR for death of 1.0 when compared with ADT alone, informed Saad.  

Tumour burden could be a prognostic and predictive factor, he said, suggesting that there was no benefit in giving chemotherapy to prostate cancer patients with low-disease volume.    

“So, tumour volume is important in making decisions and personalizing care for patients.”

For metastatic castration-resistant prostate cancer (mCRPC) patients, prostate-specific antigen (PSA) value was less predictive, while other factors such as Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH), and metastases site, were more predictive of survival. [J Clin Oncol 2014;32:671-677]    

In particular, specific sites of metastases were associated with differential OS in mCRPC patients treated with docetaxel based on a meta-analysis of data from nine clinical trials, with the worst median OS for liver metastases (13.5 months), and the longest median OS for lymph node (LN)-only disease (31.6 months).  [J Clin Oncol 2016;34:1652-1659]

“In order of significance, LN has the best prognosis, followed by bone and lung, while the worst case is liver metastases,” explained Saad.

mCRPC patients with liver metastases were less likely to survive than those with lung metastases (pooled HR for death, 1.52; p<0.0001), while lung metastases portended a worse OS when compared with nonvisceral metastases (pooled HR for death, 1.35; p=0.007).    

Combining the different prognostic factors could also predict survival, Saad said, citing a recent study which analysed data from 762 mCRPC patients treated with abiraterone acetate after docetaxel.

The study concluded that six prognostic factors were associated with a worse survival: LDH >upper limit of normal (ULN; HR, 2.31), ECOG performance status=2 (HR, 2.19), liver metastases (HR, 2.00), albumin=4 g/dL (HR, 1.54), alkaline phosphatase >ULN (HR, 1.38), and time from start of ADT to start of abiraterone acetate therapy=36 months (HR, 1.30). [Ann Oncol 2016;27:454-460]

The more risk factors that a mCRPC patient had out of the six factors, the worse their prognosis for survival, explained Saad, saying those with one or less factor had 19.7-21.3 months of median OS, while those with four or more of the factors had a median OS of about 5.3-6.1 months. 

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