Despite the rising incidence of metastatic hormone-sensitive prostate cancer (mHSPC), due in part to decreases in screening and early detection, patients now have more systemic treatment options and better survival as a result of recent advances. These new studies demonstrate that more potent forms of hormonal therapy or chemotherapy, when used earlier in the disease course and regardless of disease volume, may improve outcomes as compared to waiting until the cancer becomes hormone-therapy resistant.
A January 2020 review article in The Cancer Journal co-authored by Duke medical oncologist Andrew J. Armstrong, MD, MSc, highlights recent approvals and national guidelines updates in treatment for this patient population, which generally includes newly diagnosed patients with metastatic disease who haven’t yet started or only recently began androgen deprivation therapy (ADT).
In addition to ADT—the standard of care in this setting since 1941—systemic treatments that extend life further now include docetaxel chemotherapy for patients with high-volume disease, radiation therapy to the primary tumor for patients with low-volume disease, and potent hormone medications abiraterone, apalutamide, and enzalutamide for either high- or low-volume disease. A high volume of disease in this setting refers to prostate cancer that has spread to organs such as the liver or lungs or is widespread in the bones with four or more bone metastases.
ARCHES, for which Armstrong served as principal investigator, was a global, double-blind, phase III randomized trial that followed 1,150 men with mHSPC who were given ADT and either 160mg of enzalutamide per day or placebo. The study’s primary end point was radiographic progression-free survival, and secondary endpoints included overall survival, time to castration resistance, time to further therapy, quality of life, and time to prostate-specific antigen progression. Enzalutamide received FDA approval in December 2019 based on this work led by Duke.
At the conclusion of the study, men who received placebo and ADT alone tended to develop further metastatic spread and hormone-therapy resistance within one to two years, but those who took enzalutamide had not yet developed resistance, says Armstrong, Director of Research for the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. “Their progression to castration resistance was substantially delayed by about 60%, and this was accompanied by deeper remissions, delays in the rates of fractures, and maintained high quality of life. In many cases, the metastases disappear from the scans for many years,” he adds.
In a parallel study called ENZAMET, this same treatment with enzalutamide extended survival, and similar trials of apalutamide in the TITAN trial and abiraterone in the STAMPEDE and LATTITUDE trials also provided clear clinical benefits with early potent hormone therapies.
Armstrong also notes that new data from the UK STAMPEDE trial around radiation treatment of the primary tumor for men with lower-volume mHSPC have also been practice-changing. “In the past, if men had metastatic cancer, there was really no clear guidance on whether to treat the prostate with radiation or surgery, but now there are actually phase III trials in which men with a low burden of metastatic disease have a survival benefit from radiation,” he says. “These data suggest that the prostate itself is a major contributor to further metastatic seeding and resistance over time in these patients.”
These therapies have extended survival much more dramatically than waiting for the traditional time to use the drugs, which is when patients develop hormone resistance. “Now, when a patient is newly diagnosed with metastatic prostate cancer, it's no longer just a simple discussion of starting one specific drug; it’s a more complex discussion of which option to choose and when we should plan to treat their primary tumor, if at all,” he says. “Duke is now investigating additional approaches to further extending the survival of these patients through immunotherapy combinations in clinical trials, as our mission remains to eradicate metastatic prostate cancer and get men back to a normal life.”
With these advancements, the overall survival rate for men with mHSPC is now higher but requires much more active management over many years, Armstrong says: “It's all good news for patients, but there are added costs and side effects that need to be managed, so it's more complicated, but it’s all part of our complex discussion with patients who come to Duke with this condition.”