What PSA thresholds trigger salvage radiotherapy after radical prostatectomy?

1. Why the threshold question matters: tumor burden, detection and outcomes

Radiobiologic and clinical data indicate that sRT is most likely to cure when tumor burden is lowest, which corresponds to lower PSA levels after prostatectomy; multiple series and trials therefore report better biochemical control and metastasis‑free survival when sRT is delivered at PSA values below roughly 0.5 ng/mL ^{[6] [1] [2]}.

2. The “conventional” practical benchmark: ≤0.5 ng/mL

A substantial body of real‑world and retrospective work supports initiating sRT while PSA is ≤0.5 ng/mL, with associations reported between sRT at ≤0.5 and superior metastasis‑free survival compared with later treatment ^{[1] [7]}; major centers likewise counsel treating while PSA is below 0.5 to minimize metastatic risk ^[2].

3. Emerging lower cut points: 0.25 and 0.35 ng/mL for selected patients

Recent analyses and cohort studies have proposed lower trigger points: a multinational analysis and JCO work argue that starting sRT by a PSA of 0.25 ng/mL can avoid an increased risk of death compared with later initiation, particularly in patients with limited adverse factors, and a clinical expert voiced 0.25 ng/mL as a cut point for patients with one risk factor (eg, Gleason 8–10 or pT3–4) ^{[8] [3]}. Separately, a secondary analysis of the NRG/RTOG 0534 SPPORT dataset (noted in guideline discussion) points toward a potential alternative threshold near 0.35 ng/mL using modern RT and short‑course ADT, though that signal arose from underpowered secondary analyses ^[4].

4. How guidelines synthesize evidence: balance, individualized decision‑making, and ADT thresholds

The AUA/ASTRO/SUO guideline emphasizes using prognostic factors (PSA doubling time, Gleason grade, pathologic stage, genomic classifiers, PET imaging) rather than a single PSA number alone and notes uncertainty about optimal PSA thresholds for adding ADT; based on randomized data (eg, RTOG 9601), the panel recommends offering ADT with salvage RT to patients with higher presalvage PSA such as ≥0.7 ng/mL ^{[4] [5]}. The guideline explicitly allows clinician judgment and adjunctive risk markers to guide timing and hormone use ^[4].

5. Detection technology, insurance rules and practical delays — the 0.20 ng/mL inflection

Clinical practice is affected by imaging sensitivity and reimbursement: PSMA‑PET detection and many insurers’ coverage are more favorable at PSA ≥0.20 ng/mL, which has led some clinicians to postpone sRT to obtain better staging information — a practice that the literature warns may trade diagnostic clarity for delayed local therapy when earlier sRT might offer oncologic benefit ^[9].

6. Counterpoints and harms: randomized trials, ADT toxicity, and observation strategies

Randomized trials that informed the shift toward early salvage (eg, RADICALS‑RT, RAVES, GETUG‑AFU 16) have supported observation with early sRT rather than routine adjuvant RT for many patients, and analyses of RTOG‑9601 show that ADT confers survival benefit mainly at higher PSA levels and can increase late cardiac and neurologic toxicities when given to patients with very low presalvage PSA — underscoring that overtreatment is a real risk and decisions must weigh comorbidity and individual risk ^{[10] [11]}.

7. Practical synthesis for clinicians and patients

The best‑supported practical rule is to consider sRT promptly once PSA becomes detectable and rising, with strong evidence favoring initiation at ≤0.5 ng/mL, increasing interest in lower cutoffs (0.25–0.35 ng/mL) for patients with adverse features, and a guideline‑backed threshold of about ≥0.7 ng/mL to prompt offering concurrent ADT — all tempered by PSADT, pathologic risk, imaging, patient comorbidity and the known toxicity tradeoffs of systemic hormone therapy ^{[1] [3] [4] [5] [9]}.