Experts Review Treatment Algorithms for Prostate Cancer
Key Points
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Androgen pathway modulating (APM) therapies are the backbone of therapy for prostate cancer across treatment settings.
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In localized disease, the combination of androgen receptor pathway inhibitor (ARPi) and androgen deprivation therapy (ADT) is standard of care.
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The POSEIDON meta-analysis suggests that ADT can be avoided in patients with lower-risk disease after postoperative salvage therapy.
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For biochemically recurrent and metastatic castration–sensitive and castration–resistant disease, APM regimens can be combined with radioligand agents, PARP inhibitors, and chemotherapy based on patient risk factors.
Treatment Pathways for Different Prostate Cancer Settings
Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, discussed the treatment algorithm for prostate cancer with Scott Tagawa, MD, MS, FACP, FASCO, of Weill Cornell Medicine, including the different treatment paradigms for localized, biochemically recurrent or metastatic, castration–sensitive or castration–resistant, and BRCA–mutated disease.
Localized Prostate Cancer Treatment Algorithm
For localized prostate cancer with a favorable risk profile, the standard of care treatment is radiation, surgery, or active surveillance. For unfavorable or high-risk patients, radiation combined with ADT plays a greater role, although surgery or surveillance may still be feasible. More recently, the STAMPEDE trial showed that the addition of abiraterone, an ARPi, to ADT and radiotherapy significantly improved progression-free survival and overall survival for patients with high-risk prostate cancer.
Abiraterone may be contraindicated in patients with cardiac comorbidities. For these patients, oncologists should partner with cardiologists to discuss the severity of cardiac comorbidities and make an individualized treatment decision. There is also the potential to de-escalate the STAMPEDE regimen with shorter courses of each drug, said Dr. Tagawa.
During the discussion, the doctors discussed how the growing use of prostate-specific membrane antigen (PSMA) PET imaging has affected staging and treatment decisions. PSMA PET is very valuable for identifying potential metastases, especially with supporting evidence like high prostate-specific antigen (PSA) level or Gleason grade group, said Dr. Tagawa.
Treatments for Biochemically Recurrent CSPC
Standard of care treatments for biochemically recurrent castration–sensitive prostate cancer (CSPC) include observation, ADT alone, ADT plus ARPi, and enzalutamide. However, Dr. Tagawa stressed that oncologists should consider potentially curative local salvage therapy, such as radiation or additional surgery, before initiating any of the available APM therapies. After salvage treatment is explored, systemic therapy may be warranted in patients with poor PSA prognostic features, such as higher absolute value and quick kinetics.
The EMBARK trial showed that high-risk patients benefited from combination ADT and ARPi treatment. Conversely, the recent POSEIDON meta-analysis showed that patients with low PSA may not need additional APM treatment. Oncologists also have the opportunity to implement intermittent ADT, said Dr. Rahul Gosain.
mCSPC
For metastatic castration–sensitive prostate cancer (mCSPC), the standard of care includes ADT plus ARPi with or without chemotherapy (docetaxel). For additional options, the PSMAddition trial investigated combining lutetium-177 (177Lu)–PSMA-617 with ADT plus ARPi regimens, and the AMPLITUDE trial investigated abiraterone plus niraparib, a PARP inhibitor, in BRCA2–mutated disease. The FDA approved niraparib plus abiraterone for this indication on December 12, 2025. 177Lu–PSMA-617 is approved in metastatic castration–resistant prostate cancer (mCRPC), but has not yet been approved for mCSPC.
Overall, the majority of patients should receive ADT plus ARPi combinations, and eligible patients should receive a PARP inhibitor based on AMPLITUDE. Beyond that, intensifying treatment with the addition of 177Lu–PSMA-617 or docetaxel may be warranted for mCSPC with high disease volume or de novo metastatic diagnoses, although Dr. Tagawa said he is awaiting more data from PSMAddition data before using 177–Lu-PSMA-617 off-label.
Treating Biochemically Recurrent and Metastatic CRPC
For biochemically recurrent CRPC, the standard of care is ADT plus enzalutamide, apalutamide, or darolutamide. The standard of care for mCRPC includes these doublets, as well as 177Lu–PSMA-617 and PARP inhibitor combinations. In addition, radium-223 is approved for CRPC with bone metastases only, and sipuleucel-T is approved for asymptomatic or minimally symptomatic mCRPC.
When using radioligands, regular monitoring is necessary. In his practice, Dr. Tagawa reviews PSA characteristics and uses single-photon emission computed tomography (SPECT) imaging. Alongside this, he typically gets scans done after every 2 cycles of systemic therapy. At this point, PSMA PET/CT may not be necessary and conventional CT may be sufficient to screen for any potential metastases that SPECT could miss, said Dr. Tagawa. Based on these scans, oncologists have the opportunity to swap therapy if the disease has progressed or potentially hold therapy if the patient achieved a very good response.