Prostate-Specific Membrane Antigen PET/CT-Guided, Metastasis-Directed Radiotherapy for Oligometastatic Castration-Resistant Prostate Cancer

• Published in: Journal of Nuclear Medicine Vol. 65; no. 9; pp. 1387 - 1394
• Main Authors: Nikitas, John, Castellanos Rieger, Angela, Farolfi, Andrea, Seyedroudbari, Ameen, Kishan, Amar U, Nickols, Nicholas G, Steinberg, Michael L, Valle, Luca F, Rettig, Matthew, Czernin, Johannes, Calais, Jeremie
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 03-09-2024
• Subjects: Aged; Aged, 80 and over; Androgen receptors; Androgens; Antigens; Antigens, Surface - metabolism; Cancer therapies; Castration; Chemotherapy; Computed tomography; Criteria; Deprivation; Disease control; Glutamate Carboxypeptidase II - metabolism; Humans; Male; Medical imaging; Membranes; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Pharmaceuticals; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms, Castration-Resistant - diagnostic imaging; Prostatic Neoplasms, Castration-Resistant - pathology; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Radiation therapy; Radioisotopes; Radiotherapy, Image-Guided; Retrospective Studies; Survival; Toxic diseases; Toxicity; prostate cancer; castration resistance; metastasis-directed therapy; prostate-specific membrane antigen PET; radiation therapy
• ISSN: 0161-5505; 1535-5667; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.124.267922

Systemic treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy, androgen receptor pathway inhibitors, chemotherapy, and radiopharmaceuticals, all of which have associated toxicity. Prostate-specific membrane antigen (PSMA) PET/CT allows for higher sensitivity in detecting metastatic disease than is possible with conventional imaging. We hypothesized that PSMA PET/CT-guided, metastasis-directed radiotherapy may offer durable disease control with low toxicity rates in patients with mCRPC who have a limited number of metastases.
We retrospectively screened 5 prospective PSMA PET/CT studies for patients with mCRPC who had up to 5 sites of oligorecurrent or oligoprogressive disease on PSMA PET/CT and subsequently received definitive-intent, metastasis-directed radiotherapy to all new or progressing sites with concurrent androgen deprivation therapy. Progression-free survival, freedom from new lines of systemic therapy, and overall survival (OS) were calculated from the start of metastasis-directed radiotherapy using Kaplan-Meier analysis. Biochemical response was defined as at least a 50% decrease in prostate-specific antigen 6 mo after the start of treatment. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 5.
Twenty-four patients met the inclusion criteria with a median follow-up of 33.8 mo (interquartile range, 27.6-45.1 mo). Between October 2017 and April 2023, 11 patients (45.8%) had 1 treated site, 10 patients (41.7%) had 2, and 3 patients (12.5%) had 3. Five sites were prostate or prostate bed, 15 were nodal, 19 were osseous, and 1 was visceral. Seventeen patients (70.8%) continued their preexisting systemic therapy, whereas 7 (29.2%) started a new systemic therapy. Median progression-free survival was 16.4 mo (95% CI, 9.8-23.0 mo). The biochemical response rate was 66.7%. Median freedom from a new line of systemic therapy was 29.0 mo (95% CI, 7.6-50.4 mo). Median OS was not reached. The 2- and 4-y OS rates were 91.1% (95% CI, 79.3%-100%) and 68.8% (95% CI, 45.1%-92.5%), respectively. Grade 2 and grade 3 or higher toxicity rates were 4.2% and 0%, respectively.
PSMA PET/CT-guided, metastasis-directed radiotherapy appears to offer durable disease control with low toxicity rates for oligometastatic castration-resistant prostate cancer. Further prospective studies are needed to compare metastasis-directed radiotherapy with systemic therapy versus systemic therapy alone and PSMA PET/CT-guided versus conventional imaging-guided radiotherapy.