What imaging should be done to localize recurrence before salvage radiation therapy?

1. Why imaging matters now: precision changes treatment intent

Modern practice treats biochemical recurrence (BCR) as a heterogeneous state where the presence or absence of regional or distant disease determines whether salvage radiation is offered with curative intent; the AUA/ASTRO/SUO guideline recommends next‑generation molecular PET (PSMA‑PET) for patients being considered for salvage radiation because it better distinguishes localized from metastatic recurrence and can change management ^{[1] [4]}.

2. The recommended core tests: PSMA‑PET plus pelvic MRI

Guideline panels and recent conference summaries consistently recommend PSMA PET as the primary staging test before salvage RT and endorse adding pelvic MRI to improve local staging and guide biopsy or radiotherapy target delineation; ASCO‑GU reporting and the AUA guideline explicitly state PSMA‑PET with pelvic MRI for a more comprehensive assessment ^{[2] [1]}.

3. How often PSMA‑PET finds disease and why PSA level matters

Prospective series cited at ASCO‑GU show PSMA PET localization rates vary with PSA; one UCSF trial localized recurrent cancer in 75% of 635 men with median PSA patterns showing higher detection with higher PSA values—supporting early imaging but noting sensitivity increases as PSA rises ^[2]. The CONDOR study and related analyses reported detection and correct localization rates in the 60–87% range in appropriately selected cohorts, illustrating substantial—but not perfect—sensitivity ^[2].

4. What pelvic MRI adds—local detail and surgical planning

Panels and surgical case series stress pelvic MRI to confirm resectability and to define intraprostatic, seminal vesicle, or prostate‑bed recurrence for either focal salvage therapy or salvage prostatectomy; MRI complements PET by better characterizing anatomic extent even when PET is negative or equivocal ^{[5] [2]}.

5. Biopsy remains part of the decision mix—imaging isn’t enough

Contemporary reviews warn that post‑radiation biopsies are prone to false negatives and under‑staging and that mapping biopsies (3D‑TMB) detect recurrences that imaging can miss; guideline statements therefore endorse targeted biopsy in men without metastatic disease who are candidates for local salvage therapy, with PET/MRI guiding sampling ^{[3] [2]}.

6. Practical implications for radiation planning

When PSMA‑PET shows pelvic nodal disease, guidelines recommend incorporating those nodal sites into the radiation plan; conversely, a negative PSMA‑PET should not automatically preclude salvage prostate‑bed RT in post‑prostatectomy BCR—clinical factors and timing still guide early SRT decisions ^{[1] [6]}.

7. Limitations, access and evolving evidence

Guideline panels caution that availability of PET tracers and local expertise vary and that more sensitive imaging may change management without yet proven long‑term outcome benefits; several groups explicitly note ongoing trials and unresolved questions about whether more sensitive staging improves survival or just changes treatment patterns ^{[1] [3]}.

8. Putting it together for clinicians and patients

For a patient with rising PSA after primary therapy who is being considered for salvage radiation, the evidence‑based workup is: obtain PSMA‑PET (next‑generation molecular PET) to determine N/M status, add high‑quality pelvic MRI to delineate local anatomy and to plan biopsy or focal therapy, and perform targeted or mapping biopsy when local salvage is contemplated; counsel patients that imaging may discover occult metastases that change intent and that imaging and biopsy both have false‑negative rates that warrant cautious interpretation ^{[1] [2] [3]}.

Limitations: available sources do not provide a single uniform algorithm tied to specific PSA cutoffs beyond noting detection relates to PSA and that early SRT is more effective at lower PSA ^{[2] [6]}.