Overview of PSMA PET and salvage treatment of previously irradiated recurrent prostate cancers

Background:

Prostate cancer is prevalent in the United States and often spotlighted due to celebrity diagnoses. Recurrent prostate cancer remains a major clinical challenge, typically first indicated by a rising prostate-specific antigen (PSA) level. PSA serves as a reliable biomarker to prompt further evaluation. Recent advances in nuclear imaging—particularly prostate-specific membrane antigen positron emission tomography (PSMA PET)—have reshaped the detection and management of recurrence. PSMA PET offers higher sensitivity and specificity than conventional imaging, allowing earlier detection and guiding more precise restaging and therapeutic decisions.

The objective of this narrative review summarizes recent progress in PSMA PET imaging and emerging salvage treatments for recurrent prostate cancer following definitive radiation therapy.

Methods:

A targeted literature search was conducted via PubMed to identify studies and guidelines on innovative recurrence detection and optimal salvage interventions. Keywords included “prostate cancer recurrence,” “PSMA PET,” “androgen deprivation therapy,” “prostatectomy after radiation,” and “salvage treatment.”

Results:

Biochemical recurrence is defined by a PSA rise of ≥2 ng/mL above the post-treatment nadir, per Phoenix criteria. This triggers further assessment. PSMA PET detects local and metastatic recurrence at lower PSA levels than traditional modalities like CT and bone scans. Novel biomarkers such as circulating tumor DNA (ctDNA) are being explored to supplement PSA and imaging techniques.

First-line salvage therapy typically involves total androgen blockade: a gonadotropin-releasing hormone (GnRH) agonist or antagonist combined with an anti-androgen agent. GnRH antagonists may provide faster PSA responses and fewer side effects. Monotherapy is less favored due to limited efficacy and side effects.

For patients with poor prognostic factors (e.g., short PSA doubling time, high Gleason score, distant metastases), continuous androgen deprivation therapy (ADT) is recommended over intermittent regimens due to better survival outcomes.

Local salvage options—including prostatectomy, brachytherapy, or stereotactic radiotherapy—are technically complex post-radiation due to fibrosis and should be performed in specialized tertiary centers.

For advanced or metastatic disease, triplet therapy—combining hormone therapy, chemotherapy, and androgen receptor inhibitors—is increasingly used. Agents like Radium-223 and ^177Lutetium-PSMA-617 have demonstrated survival benefits in ALSYMPCA and VISION trials, respectively.

Lastly, supportive care is vital, addressing psychological distress, preserving quality of life and improving treatment adherence.

Conclusion:

Recurrent prostate cancer is usually signaled by rising PSA levels and is more accurately characterized with PSMA PET imaging. Salvage management depends on disease burden and patient-specific factors, ranging from systemic therapy to complex local procedures. Early detection and multidisciplinary care are essential to optimize outcomes.

Fatlinda Berisha Doctor of Medicine, who complete her studies in General Medicine at the University of Prishtina “Hasan Prishtina.” She has a compassion for helping patients and performing research in cancer. I collaborated with seven other classmates in the cancer research team of Professor Patricia Tai in Canada who serves as a mentor for them all.