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A review of 22 trials led the American Society of Clinical Oncology (ASCO) to issue updates to its mCRPC systemic therapy guideline.

For patients with metastatic castration-resistant prostate cancer (mCRPC), the choice of systemic therapy will differ based on the patient’s previous treatment for castration-sensitive prostate cancer (CSPC), according to an American Society of Clinical Oncology (ASCO) guideline update published online in the Journal of Clinical Oncology.

“Depending upon prior treatment received, androgen receptor pathway inhibitors (ARPIs: enzalutamide, abiraterone with prednisone), poly(ADP-ribose) polymerase inhibitors (PARPi), chemotherapeutic agents (docetaxel, cabazitaxel), radiopharmaceuticals (radium 223, ¹⁷⁷Lu-prostate-specific membrane antigen [PSMA]-617), and sipuleucel-T have demonstrated an overall survival benefit for patients with mCRPC,” wrote first author Rohan Garje, MD, of the Miami Cancer Institute, and coauthors of the update.

The guideline update was based on findings from a systematic review of 22 trials spanning 14,707 patients.

“Treatment for mCSPC [metastatic CSPC] has evolved and intensified rapidly from single-agent ADT [androgen-deprivation therapy], with most patients currently receiving doublet and triplet regimens,” the authors wrote. “Our current guidelines take into consideration this heterogeneity in frontline therapy for mCSPC for specific recommendations for their treatments for mCRPC.”

Updates to the Guideline

According to the guideline update, androgen-deprivation therapy should be used indefinitely in patients with mCRPC. At the earliest opportunity, somatic genetic testing should be conducted, and palliative care should also commence, in alignment with ASCO’s guidelines for Germline and Somatic Genomic Testing for Metastatic Prostate Cancer and Palliative Care for Patients With Cancer.

To lower the risk of skeletal-related events, the panel advised the use of bone-protective agents in patients with mCRPC and bone metastases.

For patients with mCRPC with BRCA1/2 alterations who did not previously receive ARPI, the guideline recommends the combination of ARPI and PARPi. Patients with BRCA1/2 alterations who received prior ARPI should receive PARPi monotherapy.

Patients with mCRPC who received prior ARPI are advised to receive docetaxel chemotherapy. For those with prior ARPI and docetaxel chemotherapy, ¹⁷⁷Lu-PSMA-617 or cabazitaxel chemotherapy are recommended.

Patients with symptomatic bone–only disease without known visceral metastases or large nodal metastatic disease should receive radium 223, per the update.

The panel reported limited available evidence to inform the optimal sequencing of mCRPC regimens.

Mitigating Patient Confusion

“The choices on the sequencing of different treatments and what side effects to accept create significant confusion for patients with CRPC,” the authors wrote. “Patients and physicians should work together to incorporate more second opinions in complex and challenging situations.”