Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

Radiation therapy (RT) for prostate cancer has gastrointestinal and genitourinary toxicities, greater with baseline lower urinary tract symptoms (LUTS) and larger prostate volume (PV). Prostate artery embolization (PAE) improves LUTS and PV before RT. This study evaluates the durability of LUTS improvement from neoadjuvant PAE before prostate RT and oncologic outcomes. We retrospectively identified patients receiving definitive prostate RT following PAE from a prospective database, including International Prostate Symptom Scores (IPSS), pre- and post-PAE MRI PV, and toxicity per CTCAEv5.0. Primary objective was LUTS by IPSS. Secondary objectives included biochemical recurrence-free survival (bRFS), local recurrence, and distant metastasis. From 9/2017–5/2024, 82 patients underwent PAE before RT, with 30.5 % having unfavorable intermediate risk. RT consisted of conventional fractionation (n = 21), moderate hypofractionation (n = 42), SBRT (n = 11), and EBRT/brachytherapy boost (n = 8); a subset of patients received androgen deprivation therapy. Pelvic lymph nodes were treated in 28 (34 %) patients. Median pre-PAE IPSS was 18 (range 2–34), PV 90 cc (14.2–240), and PSA 8.4 ng/mL (0.02–125.5). Post-PAE, mean IPSS reduction was 10.7 points (−13–30). Mean PV reduction was 30.9 cc (−9–136) or 32 %. PAE converted 52 % of patients contraindicated by size/IPSS for brachytherapy/SBRT. Post-RT, mean IPSS changes at 3, 6, 12, 18 and 24 months were −8.7, −8.5, −9.5, −8.9, and −7.6, respectively (p < 0.001). At 24.2-month median follow-up, 1 local recurrence occurred. Two-year bRFS was 92 % for non-metastatic patients. Urinary improvement is durable after RT in men with large prostates and/or high LUTS burden with neoadjuvant PAE, and no increased risk of recurrence at intermediate-term follow-up. Further investigation is warranted.