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. 2025 Sep 3;17(17):2893.
doi: 10.3390/cancers17172893.

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

Ruiqi Li  1 , Mu-Han Lin  1 , Nghi C Nguyen  2 , Fan-Chi Su  1 , David Parsons  1 , Erica Salcedo  1 , Elizeva Phillips  1 , Sean Domal  1 , Aurelie Garant  1 , Raquibul Hannan  1 , Daniel Yang  1 , Asim Afaq  3 , MinJae Lee  4 , Orhan K Oz  3 , Neil Desai  1
Affiliations

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

Ruiqi Li et al. Cancers (Basel). .

Abstract

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 (n = 3) or CBCT-based ART (n = 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 (p = 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.

Keywords: MR-linac; PSMA-PET; adaptive radiotherapy; prostate cancer; stereotactic ablative radiotherapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Trial scheme.
Figure 2
Figure 2
Workflow for PSMA-PET-guided adaptive radiotherapy incorporating sequential imaging and planning steps across offline and online treatment planning systems (TPSs). Role responsibilities are indicated by color-coded professional icons.
Figure 3
Figure 3
Individual patient-level trends in GTV boost volume and organ-at-risk (OAR) dose metrics across three adaptive planning stages: initial (Plan_initial), post-ADT (Plan_mb1), and mid-treatment (Plan_mb2).
Figure 4
Figure 4
Bar plot illustrates treatment time differences for each fraction relative to the first fraction across five patients treated on Ethos (CBCT-Linac) and Unity (MR-Linac) platforms.
Figure 5
Figure 5
Representative axial images showing serial PSMA-PET signal and corresponding radiotherapy (RT) dose distributions for three adaptive boost plans: initial (Plan_initial), post-ADT (Plan_mb1), and mid-treatment response (Plan_mb2). (Left column) shows PSMA-PET/MRI fusion images with evolving dominant intraprostatic lesion (DIL) contours. (Right column) displays corresponding RT plans with isodose lines (2500–5000 cGy) illustrating progressive dose conformality and reduced high-dose exposure with GTVmb adaptation.
See this image and copyright information in PMC

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