Johann De Bono, MB CHB, PhD, MSC
Layering of therapies and advances in next-generation imaging and sequencing are key reasons that outcomes are improving in advanced prostate cancer (PC). However, optimal timing of therapies will be essential to ensure that patients benefit from all available drugs that improve survival, according to experts who participated in a recent Peer Exchange™
discussion. “We’ve got to find drugs that improve survival, and you want as many of your patients to benefit from as many of those drugs as possible,” said Chris Parker, MD, FRCR, MRCP. “You don’t want them to die after having 1 or 2.”
The panelists discussed the importance of next-generation imaging for identifying early metastases, and which patients with rising prostate-specific antigen (PSA) levels should receive aggressive therapy. Other topics included recent studies showing that addition of docetaxel or abiraterone acetate (Zytiga) to androgen-deprivation therapy (ADT) improved survival in metastatic, hormone-sensitive PC; sequencing or combining therapies for metastatic castrationresistant PC (mCRPC); and new therapies for metastatic disease, including androgen receptor (AR)-targeted therapies, immune checkpoint inhibitors, and prostate-specific membrane antigen (PSMA)–directed radioligand therapy.
Gains in Making Earlier Assessments
Early detection and monitoring of treatment response in mPC are among the most important advantages of the newest next-generation imaging modalities, such as whole-body, diffusion-weighted magnetic resonance imaging (WB-DWI) and PSMA-positron emission tomography (PET), according to Bertrand Tombal, MD, PhD. Parker added that WB-DWI is markedly better than older methods, such as PSA testing or computed tomography (CT), for assessing response to treatment with radium-223 in patients with bone metastases. “For the first time, we can certainly see who’s benefiting and who’s not,” he said.
However, Tombal cautioned that these highly sensitive tests may have lower specificity and may lead to unnecessary treatment of noncancerous lesions. For example, he noted that PSMA-PET performed in patients with rising PSA levels may show an oligometastatic deposit that is easily removable with surgery or treatable with radiation therapy (RT). However, he stated that based on findings, 20% of these lesions are noncancerous, so treatment of all suspicious lesions may constitute overtreatment.
Conversely, these imaging modalities may be used as a follow-up to PSA measurement to prevent unnecessarily aggressive treatment in individuals with rising PSA and negative imaging. “People often say...you’re treating a lot of patients based on [PSMA-PET], but they don’t see the other part, which is the number of patients we save from aggressive treatment because they have a negative PET PSMA [or] a negative whole-body MRI,” said Tombal.
The panelists also discussed the potential for next-generation imaging to delay the administration of ADT by detecting more patients with oligometastatic disease for which RT and surgery are still viable options. “I think there’s far too much use of early ADT,” said Parker. “My bias is to treat radically where appropriate with radiotherapy or even with surgery [for] oligometastatic disease.”
Parker added that RT of small oligometastatic lesions may provide the possibility of cure for a small proportion of patients. “If I had oligometastatic disease, I could have hormonal therapy alone and be certain of not being cured, or I could have radical radiotherapy with a chance of being cured.”
ADT Partners in the Front-line Setting
Until recently, ADT alone was the standard of care (SOC) for metastatic hormone-sensitive PC. However, data from the CHAARTED1 and STAMPEDE2 trials showed that addition of docetaxel to ADT significantly improves survival, and the LATITUDE trial3
showed that addition of abiraterone, a drug that blocks endogenous androgen synthesis, to SOC improves overall survival (OS) and radiographic progression-free survival. The results from these trials provide 2 new options for treatment of metastatic hormone-sensitive PC. However, the panelists disagreed on which agent should be added to ADT in the frontline setting.
Although Parker noted that underpowered data from STAMPEDE (from the time when both the docetaxel and abiraterone arms were open) suggest no difference in OS when docetaxel or abiraterone are added to ADT, he stated that the fewer adverse effects associated with abiraterone would likely make it more favorable for patients in the frontline setting. Parker added that although some data suggest that OS is similar between the 2 agents, time to progression tends to be much longer with abiraterone.