Treatment of Oligometastatic Disease in Prostate Cancer

Educational Objectives

The goal of this program is to improve the management of oligometastatic prostate cancer (OMPC). After hearing and assimilating this program, the clinicians will be better able to:

1. Recommend evidence-based treatment options available for patients with OMPC.

Summary

Definitions: the CHAARTED criteria (Sweeney et al, 2015) define high-burden disease as the presence of visceral metastasis or ≥4 bone lesions, with >1 lesion beyond the vertebral bodies and pelvis; low-burden disease is characterized by ≤3 bone lesions (with 1 outside the pelvis or vertebrae) without visceral metastasis; this definition relies on standard bone scanning and computed tomography (CT); the ESTRO-ACROP Delphi consensus (Zilli et al, 2022) defines oligometastasis as ≤5 lesions; the HORRAD trial (Boevé et al, 2019) refined the definition of oligometastasis to <5 lesions

Treatment of the prostate with concurrent oligometastatic disease: the STAMPEDE trial (Parker et al, 2018) — showed no difference in median or overall survival at 3 yr among patients with metastatic cancer who received androgen deprivation therapy (ADT) vs ADT plus low-dose prostate radiation; radiation especially improved 3-yr overall survival and overall failure-free survival for patients with a low metastatic burden; no differences were noted regarding symptomatic local events or adverse events; Parker et al (2022) — reaffirmed the advantage of radiation in low-burden vs high-burden disease after 5 yr, with no differences in quality of life (QOL) or symptomatic local events; local radiation to the prostate significantly improved overall survival in patients with low-burden disease but made no difference in patients with high-burden disease; local radiation improved overall survival for men with low-burden oligometastatic prostate cancer (OMPC) with no effect on long-term QOL

Treatment of metastatic prostate cancer: prostate-specific membrane antigen (PSMA) positron emission tomography (PET) may not identify as many men with low-burden disease vs high-burden disease; STOMP trial (Ost et al, 2020) — demonstrated benefits in ADT-free survival with metastasis-directed therapy (MDT) compared with surveillance; treatment was beneficial regardless of nodal status and prostate-specific antigen doubling time; the authors recommended advanced imaging with PSMA PET and a short course of ADT at the time of MDT; ORIOLE trial (Phillips et al, 2020) — favored treatment of OMPC with metastasis at 1 to 3 sites with stereotactic ablative radiotherapy (SABR) vs observation, leading to improved progression-free and biochemical survival; treating metastatic disease demonstrated advantages in progression-free survival (PFS); data revealed the presence of expanded T-cell receptors in participants treated with SABR, suggesting a positive immunologic response; the screening of tumors for high-risk mutations showed that patients without the high-risk mutation experienced significantly longer PFS with SABR; even with a high-risk mutation, there was improvement in treating metastatic sites, but the improvement was more substantial without high-risk mutations

EXTEND trial (Tang et al, 2023): noted extension of median PFS with ADT plus MDT, compared with ADT alone; significant prolongation of PFS was noted following testosterone recovery

ESTRO-ACROP Delphi consensus for OMPC (Zilli et al, 2022): 88% of the consensus group preferred PSMA PET for staging and restaging of castrate-sensitive or castrate-resistant PC with oligometastasis; oligometastasis was defined as ≤5 lesions; age did not disqualify a patient from MDT; de novo oligometastatic castrate-sensitive PC — PSMA PET should confirm disease initially staged with standard imaging; treatment should cover all sites, including primary nodes and bone metastasis, and should include systemic treatment; oligorecurrent hormone-sensitive PC — the time interval since original treatment was not a consideration for candidacy; systemic therapy plus MDT is recommended for all sites; ADT should take place for ≥6 mo; oligoprogressive hormone-resistant PC — MDT is recommended for all lesions; change systemic treatment

Readings

Boevé LM, Hulshof MC, Vis AN. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospectiandomizedsed clinical trial: data from the HORRAD trial. Eur Urol. 2019;75(3):410-418. doi:10.1016/j.eururo.2018.09.008; Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446-453. doi:10.1200/JCO.2017.75.4853; Parker CC, James ND, Brawley CD, et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: long-term results from the STAMPEDE randomised controlled trial. PLoS Med. 2022;19(6):e1003998. doi:10.1371/journal.pmed.1003998; Radwan N, Phillips R, Ross A, et al. A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE). BMC Cancer. 2017;17:1-9. doi:10.1186/s12885-017-3455-6; Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi:10.1056/NEJMoa1503747; Tang C, Sherry AD, Haymaker C, et al. Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer: the EXTEND phase 2 randomized clinical trial. JAMA Oncol. 2023;9(6):825–834. doi:10.1001/jamaoncol.2023.0161; Zilli T, Achard V, Dal Pra A, et al. Recommendations for radiation therapy in oligometastatic prostate cancer: an ESTRO-ACROP Delphi consensus. Radiother Oncol. 2022;176:199-207. doi:10.1016/j.radonc.2022.10.005.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Crook was recorded at SouthWest Prostate Cancer Symposium, held April 13-15, 2023, in Scottsdale, AZ, and presented by Grand Rounds in Urology. For more information about the upcoming CME activities from this presenter, please visit https://grandroundsinurology.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

UR470702

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.