The second opinion case is a 59-year-old African American male who was recently found to have an elevated PSA at a community screening event. PSA was 21.3 ng/mL, confirmed by repeat PSA. He was seen by a local urologist and underwent a prostate biopsy showing multiple cores of Gleason Grade Group 1 prostate cancer. Given the elevated PSA, a bone scan was obtained, which showed a single sacral lesion. Follow-up prostate-specific membrane antigen (PSMA) positron emission tomography (PET) confirmed the avid lesion concerning for metastatic disease (Figure 1). Given the concern for the de novo metastatic prostate cancer, the patient was started on leuprolide and referred for a second opinion.

This case represents an opportunity for multidisciplinary patient care involving the urologist, the medical oncologist, and radiation oncologist. Additional team members should include a genetic counselor. Multidisciplinary care is recommended as part of the AUA guidelines on men with advanced prostate cancer.

PSMA PET has been shown to increase the sensitivity of detection for metastases compared to conventional imaging in the proPMSA trial.¹ However, PSMA PET may be less sensitive for bone metastasis in rib lesions, and degenerative joint disease or Paget’s may also cause false positives. MRI can be useful in further defining the presence of destructive lesions. A biopsy of this metastatic site may be the most informative, but tissue from any easily accessed source could also be considered for somatic (tumor) testing. The diagnostic yield of a bone biopsy varies but may be as high as 86% in experienced groups in recent reports.

Table 1. Phase 3 Trials of Prostate-Directed Therapy in Low-Volume Metastatic Prostate Cancer

The treatment goals for de novo oligometastatic disease includes considering systemic therapy primarily, but also prostate directed, lymph node and possibly therapy to this metastatic site for this young healthy patient. Dr Jarrard highlighted that patients diagnosed with metastatic prostate cancer are living increasingly longer lives and treatment of the primary reduces micrometastatic shedding and improves local control. Several studies suggest that treating the prostate may also improve long-term outcomes and reduce subsequent local complications.² While recent clinical trials have shown that radiation improves overall survival in patients with low-volume oligometastatic disease, ongoing phase 3 trials such as SWOG 1802 or SIMCAP may eventually provide evidence for the surgical treatment of the prostate in patients with metastatic prostate cancer (Table 1). In the absence of randomized trials that provide definitive support for the surgical removal of the prostate in oligometastatic disease, this is not recommended in the AUA guidelines at present.

Table 2. Clinical Trials Evaluating Treatment Intensification With Improved Overall Survival in Metastatic Prostate Cancer Patients

From the perspective of radiation therapy, a consideration in patients with de novo oligometastatic prostate cancer includes which targets may benefit from radiation. Options include radiation to the prostate, to the pelvic lymph nodes, and also treatment directed to the metastatic foci. With low-volume metastases, particularly solitary metastatic lesions, it is important to consider if the patient is truly metastatic.

Table 3. Patient Demographics of Participants of Systemic Therapy Trials in Metastatic Prostate Cancer

Dr Seibert presented a similar patient from his practice. The 63-year-old patient had a history of elevated PSA (15 ng/dL) and a biopsy that showed Gleason 4 + 3 = 7 in 8/12 cores. Evaluation with a bone scan showed a focal right iliac lesion that was confirmed avid on PSMA PET. However, imaging from 7 years prior showed the lesion was present, unchanged, and benign appearing (Figure 2).

When considering radiation to the prostate in an oligometastatic prostate cancer patient, the STAMPEDE trial evaluated patients with a new diagnosis of M1 prostate cancer on conventional imaging.³ There was an overall survival benefit in patients with low metastatic burden, which was defined as 1 to 3 bone lesions anywhere, or ≥ 4 bone metastases if only in the spine or pelvis, and no visceral metastases.

Considering treatment of metastatic lesions, the evidence is less clear. SABR-COMET showed an overall survival benefit across multiple cancer types in a small phase 2 trial (n = 99, P = .09). Other trials (STOMP, ORIOLE) investigating metastasis-directed therapy in a distinct clinical context (recurrent disease), with the goal of delaying start of ADT, have shown mixed signals. There is currently little evidence to support treatment of pelvic lymph nodes with a negative PSMA PET for patients with metastatic prostate cancer.

Dr Seibert concluded that for patients with oligometastatic prostate cancer current evidence supports radiation to the prostate. However, metastasis-directed treatment has not shown clear evidence of benefit. He suggested that we continue to enroll patients in active clinical trials (TERPS, TRITONS, SABR-COMET-3, SABR-COMET-10). For pelvic lymph nodes in a patient with visible distant metastasis and no visible nodal metastasis on PSMA PET, there is not yet evidence to support radiation to the pelvis.

Medical oncologists have benefited from a growing number of treatment options for systemic therapy in patients with metastatic prostate cancer. Several of these options were evaluated in patients stratified by high- and low-volume disease. Dr Yu reviewed trials with overall survival benefit and highlighted the variety of treatment options (Table 2). While combined hormonal and chemotherapy regimens have become common, recently treatment intensification with triplet therapy has been considered.

Dr Yu highlighted the patient demographics across the systemic therapy trials (Table 3). When considering patients receiving triplet combination therapy, he highlighted that a majority of patients in PEACE-1 and ARASENS had high-volume disease and were de novo metastatic.^4,5 This suggests that the primary benefit of treatment intensification with triplet combination therapy would be in patients who present with high-volume, de novo disease as opposed to patients with low-volume or metachronous metastatic prostate cancer.

He highlighted 2 upcoming trials to evaluate the potential benefit of docetaxel compared with combined hormonal therapy. These include the Alliance ASPIRE trial and the SWOG Triple Switch trial. He concluded that evidence suggests a low utilization of treatment intensification. He recommended early and frequent use of treatment intensification with one of several combinations, including triple combination therapy for those with high-volume de novo metastatic prostate cancer patients.