A mix of treatments may extend life for men with aggressive prostate cancer

Charlie Schmidt

Editor, Harvard Medical School Annual Report on Prostate Diseases

For men diagnosed with aggressive cancer that’s confined to the prostate and nearby tissues, the overarching goal of treatment is to keep the disease from spreading (or metastasizing) in the body. Doctors can treat these men with localized therapies, such as surgery and different types of radiation that target the prostate directly. And they can also give systemic treatments that kill off rogue cancer cells in the bloodstream. Hormonal therapy, for instance, is a systemic treatment that kills prostate cancer cells by depriving them of testosterone, which fuels their growth.

Now a new study shows that a mix of different treatments, or a “multimodal” approach to prostate cancer therapy, lengthens survival in men who have this diagnosis. The study was limited to men with Gleason 9 and 10 cancers. The Gleason grading system ranks tumors by how likely they are to spread, and 10 is the highest rank on the scale.

“The takeaway finding is that men with high-grade, localized prostate cancer do better when they get multimodal care,” said Dr. Amar Kishan, an assistant professor of radiation oncology at the University of California, Los Angeles David Geffen School of Medicine, who led the study. “If they can tolerate it, then that’s what should be offered.”

Kishan and collaborators from 12 large hospitals in the United States and Norway pooled nearly 20 years of patient data from their respective institutions. The 1,809 men included in the study had each been treated in one of three different ways:

  • with surgery to remove the prostate
  • with a combination of external beam radiation (which directs high-energy rays at the tumor from sources outside the body) directed at the prostate, along with anti-testosterone hormonal therapy
  • with hormonal therapy given together with external beam radiation and brachytherapy (which involves placing radioactive beads directly into the prostate gland).

After an average of five years of follow-up, 3% of the men given all three treatments (external beam radiation, brachytherapy, and hormone therapy) had died from prostate cancer. By contrast, 12% of the men treated with a combination of hormonal therapy and external beam radiation, and 13% of the men treated with surgery only, had died of their illness. Findings of metastatic cancer were similar, averaging 8% in the group given all three treatments, and 24% in the two other groups.

Side effects data from each group were not available.

This is the largest study yet to compare the three approaches, and importantly, it was restricted to men who began treatment no earlier than 2000. Radiation therapy has improved over time: the doses are higher and the treated areas are more precisely defined. Therefore, the evaluated approaches are consistent with the kind of treatments men would still get today.

Kishan said it’s possible that combining hormonal therapy with high-dose radiation and brachytherapy eliminates cancer in the prostate completely, so that metastases are held in check. Or, he says, radiation might stimulate the immune system to attack cancer. These hypotheses are now under investigation by researchers around the world.

Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, said the study adds to growing evidence that therapies directed solely to the prostate gland, namely radiation or surgery by itself, may be improved by adding other treatments; in this case, hormonal therapy and a second form of radiation. “The study didn’t evaluate the addition of hormonal therapy to surgery, which would have been of interest,” he added. “However, the findings support multimodal therapy, though many unknowns, such as the potential for greater long-term side effects, still need to be addressed.”

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