Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) has emerged as a game-changing imaging modality in prostate cancer, offering superior sensitivity and specificity compared to conventional imaging techniques. Its increasing adoption has significantly influenced radiotherapy decision-making, yet its true clinical impact remains under investigation. This narrative review explores the role of PSMA-PET/CT in guiding radiotherapy decisions across different clinical scenarios, from primary treatment planning to biochemical recurrence and oligometastatic disease. We assess its impact on target delineation, treatment modifications, and overall patient management while addressing existing knowledge gaps.

Background/Objectives: In Spain, pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related death, with only 20% of patients eligible for surgery at diagnosis. For the remaining majority, prognosis is poor and effective non-surgical strategies are needed. Stereotactic MR-guided adaptive radiotherapy (SMART) may facilitate the delivery of ablative doses of radiation safely with low toxicity. This study reports the first national experience in Spain with SMART for patients with borderline resectable (BRPC) or locally advanced pancreatic cancer and evaluates its feasibility, safety, and early clinical outcomes. Methods: A prospective observational study was conducted including 28 patients with histologically confirmed BRPC or LAPC treated between August 2023 and December 2024. All patients received induction chemotherapy—mainly FOLFIRINOX (57.1%)—followed by SMART delivered in five fractions (40–50 Gy) using a 0.35T MR-guided linear accelerator. Daily online adaptive recontouring and replanning were performed for all 140 treatment fractions. Toxicities were assessed using CTCAE v5.0, and survival outcomes were estimated using Kaplan–Meier analysis. Results: The median patient age was 67 years, and 71.4% of tumors were located in the pancreatic head. At a median follow-up of 7.4 months after SMART (12.25 months from diagnosis), 6-month local progression-free survival (LPFS) was 89.3% from the start of SMART and 82.1% from diagnosis. Distant progression-free survival (DPFS) at 6 and 12 months was 92.9% and 68.2%, respectively. Median progression-free survival (PFS) was 11.5 months, and the median treatment-free interval was 5.7 months. Median overall survival (OS) was not reached; 6- and 12-month OS rates were 89.3% and 74.1%, respectively. Treatment-related toxicity was limited to grade 2 abdominal pain in 14.3% of patients, with no grade ≥3 adverse events attributed to SMART. Conclusions: SMART is a feasible and safe treatment modality for BRPC and LAPC in real-world clinical practice. These encouraging early outcomes support further clinical investigation and broader implementation.