Clinical Implementation of PSMA-PET Guided Tumor Response-Based Boost Adaptation in Online Adaptive Radiotherapy for High-Risk Prostate Cancer.

PURPOSE OR OBJECTIVE

To evaluate the feasibility and clinical utility of integrating sequential PSMA-PET imaging into an offline-online adaptive workflow for response-based dominant intraprostatic lesion (DIL)-boosting high-risk prostate cancer treated with stereotactic ablative radiotherapy (SABR).

MATERIALS AND METHODS

As part of a prospective trial, patients were treated on MR- or CBCT-guided adaptive radiotherapy (ART) systems with prostate/pelvic node 5-fraction SABR (36.25 Gy/25 Gy) with DIL boost (50 Gy). Whereas traditional DIL boost volumes delineate full pre-therapy imaging-defined disease (GTVinitial), this study serially refined DIL boost volumes based on treatment response defined by PSMA-PET scans after neoadjuvant androgen deprivation therapy (nADT, GTVmb1) and fraction 3 SABR (GTVmb2). DIL delineation employed PET-PSMA fusion to CT/MR simulation and was guided by a rule-based %SUVmax threshold approach. Comparisons of GTV volumes and OAR dosimetry were performed between plans using GTVinitial versus GTVmb1/GTVmb2 for DIL boost, for each of the initial cohorts of five patients from the initially treated cohorts.

RESULTS

Five patients treated on MR-Linac ( = 3) or CBCT-based ART ( = 2) were analyzed. Three patients exhibited complete imaging response after nADT, omitting GTVmb boosts. Offline GTVmb refinements based on PSMA-PET were seamlessly integrated into ART workflows without introducing additional treatment time. DIL GTV volumes significantly decreased ( = 0.03) from an initial mean of 11.4 cc (GTVinitial) to 4.1 cc (GTVmb1) and 3.0 cc (GTVmb2). Dosimetric analysis showed meaningful reductions in OAR doses: rectal wall D0.035 cc decreased by up to 12 Gy, while bladder wall D0.035 cc and V18.3 Gy reduced from 52.3 Gy and 52.3 cc (Plan_initial) to 42.9 Gy and 24.9 cc (Plan_mb2), respectively. Urethra doses remained stable, with minor reductions. Sigmoid and femoral head doses remained within acceptable limits. Online adaptation efficiently addressed daily anatomical variations, enabling simulation-free plan re-optimization.

CONCLUSION

PSMA-PET-guided adaptive microboosting for HRPCa SABR is feasible and effective. Standard MR-Linac and CBCT systems offer practical alternatives to BgRT platforms, enabling biology-driven dose personalization and potentially reducing toxicity.