New Marker Could Help Detect Need for More Aggressive Prostate Cancer Treatment


A prostate-specific antigen nadir greater than 0.5 ng/mL following radiation and androgen deprivation therapy seems to identify men prior to PSA failure who are at high-risk for death, and would thus require more aggressive treatment for their prostate cancer.

Trevor J. Royce, MD

Trevor J. Royce, MD

A prostate-specific antigen (PSA) nadir (the lowest level a PSA drops following treatment) greater than 0.5 ng/mL following radiation and androgen deprivation therapy seems to identify men prior to PSA failure who are at high-risk for death, and would thus require more aggressive treatment for their prostate cancer, according to the results of a recent study inJAMA Oncology.

The study looked at data from a randomized trial of 206 men treated with either radiation or radiation plus 6 months of hormonal therapy and compared early markers of prostate cancer death to identify men at risk of dying early.

In an interview withTargeted Oncology, Trevor J. Royce, MD, senior resident, Department of Radiation Oncology, Brigham and Women's Hospital, discussed the findings of this study and how they may change designs of future clinical trials in prostate cancer.

TARGETED ONCOLOGY:What was the rationale for conducting this study?


Clinical trials in early prostate cancer can take a long time to report on, sometimes over a decade. People have been investigating early-reporting endpoints, and these have been proposed, but it’s been unknown until now which may be better than the other. And these early endpoints would be a way to speed up the results of trials.

TARGETED ONCOLOGY:How was your study carried out, and what were the most significant findings?


We used data from a randomized trial of 206 men who were treated with radiation or radiation and 6 months of hormone therapy. Then we compared early markers for prostate cancer death to identify who, in that cohort, would be at risk for dying early from their prostate cancer.

We found that, of all the possible early endpoints that we studied, how low a PSA blood test falls to after treatment with radiation and hormone therapy, appears to be the best predictor. Specifically, if the PSA does not get below half a point, then that patient is very likely to die of prostate cancer if given standard treatment for recurrence. These men deserve enrollment on clinical trials in order to properly save their lives.

TARGETED ONCOLOGY:What impact do you expect these results to have on the overall treatment landscape?


This newly defined endpoint can be used to enroll men today on clinical trials whose hope it is to take a prostate cancer that appears to be aggressive based on this metric, and potentially incurable, and make it curable with more aggressive care under the context of a clinical trial.

To our knowledge, this is the first study of its kind to really compare these endpoints head to head to identify one that may be superior to the others.

TARGETED ONCOLOGY:What would more aggressive treatment entail for these patients, and are there any concerns for heightened toxicity?


There are novel forms of hormonal therapy, or cytotoxic chemotherapy. Hormonal therapy includes agents like enzalutamide (Xtandi) or abiraterone (Zytiga), and cytotoxic chemotherapy refers to docetaxel, which has been shown to prolong survival in men with metastatic and castration-resistant prostate cancer. So these are potential therapies that we’re considering in the context of a clinical trial for our cohort. These more aggressive treatments could bring on more toxicity, so that’s something we have to be aware of.

TARGETED ONCOLOGY:Are there any next steps planned following your results?


The next step would be to use this newly defined endpoint and enroll men on clinical trials and take an aggressive cancer and make it curable. That information can be used as entry criteria in clinical trials.

TARGETED ONCOLOGY:Overall, what are some of the biggest remaining challenges in this disease, and how can they be addressed?


There are certainly many challenges. A major one is that, despite it being a localized disease, two-thirds of all prostate cancer deaths observed are from men with localized disease who eventually develop metastasis. As we know, prostate cancer is the second leading cause of male death in the United States. About 26,000 people died in 2016 of prostate cancer, so this is certainly an area that we can improve upon tremendously, and hopefully this study will lead us down that path.


Royce TJ, Chen MH, Wu J, et al. Surrogate end points for all-cause mortality in men with localized unfavorable-risk prostate cancer treated with radiation therapy vs radiation therapy plus androgen deprivation therapy—a secondary analysis of a randomized clinical trial.JAMA Oncol. doi:10.1001/jamaoncol.2016.5983.

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