New research led by UC Davis Comprehensive Cancer Center revealed a link between bone metabolism biomarkers and survival among men who were recently treated with androgen deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC). The study analyzed results from a SWOG Cancer Research Network phase 3 trial of nearly 1,000 patients who were being administered ADT, including some who were also on the novel hormonal therapy orteronel. Bone biomarkers for both bone loss and bone formation were measured in HSPC patients enrolled in the trial. ADT sharply reduces production of the male sex hormone testosterone, which prostate cancer cells ordinarily need to grow.

The researchers found that elevated bone biomarkers were associated with an increased risk of death. Bone biomarkers have been found to influence overall survival in men with castration-resistant prostate cancer (CRPC), which continues to grow even after testosterone levels have been greatly reduced. However, bone biomarkers have not been fully established for HSPC.

“Our findings show that high levels of bone turnover biomarkers are associated with a shorter lifespan in men newly diagnosed with metastatic HSPC,” said cancer center Director Primo “Lucky” Lara Jr., who was one of the key investigators of the study. “In the future, knowing one’s bone biomarker status could improve how we predict patient outcomes and enhance treatment considerations for men with HSPC.”

Managing bone health during prostate cancer treatment

A finely balanced interaction between cells that rebuild bone and cells that destroy bone is common in men with advanced prostate cancer. Prostate cancer in these men often spreads to their bones, a common source of pain and fractures that can affect their survival.

In addition, men with metastatic HSPC are typically treated with ADT, which disrupts bone turnover and contributes to the development of osteopenia, osteoporosis, and other bone diseases. Previous studies have shown that elevated levels of blood-based biomarkers of bone turnover predict survival in men with CRPC and that bone-targeted therapy may help patients with highly elevated markers.

Teaming up with Lara was fellow cancer center clinical scientist Mamta Parikh. She is also the cancer center’s director of genitourinary malignancies.

“Ultimately, our findings add to the growing understanding of the complex interplay between cancer and bone metabolism, which will also help us design future clinical trials,” Parikh said.

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Further maximizing SWOG study

Parikh did additional research, leveraging the same SWOG study to determine if early prostate-specific antigen (PSA) test results, especially in tandem with treatment, can be used to predict the survival probability of people with prostate cancer.

“The study focused on how well PSA readings at three months and seven months of treatment correlated to overall survival,” Parikh said. “Our results showed that regardless of whether clinical trial participants took bicalutamide or orteronel, if their PSA dropped below 0.2, those patients in general did much better with longer overall survival than those whose PSA was greater than 4.0 at seven months.”

Parikh’s findings also signal the need for new, more aggressive interventions for patients whose PSA values at those two intervals remain high.