Radiotherapy In Prostate Cancer Patients Research Articles

Metastasis-Directed Stereotactic Body Radiotherapy in Prostate Cancer Patients Treated with Systemic Therapy and Undergoing Oligoprogression: Report on 11 Consecutive Cases

Background: Stereotactic body radiotherapy (SBRT) targeted at metastatic sites of disease progression is emerging as a potential therapeutic approach for managing oligoprogressive prostate cancer. However, a definitive benefit has yet to be demonstrated. Herein, we present our institution’s experience with this treatment approach. Methods: From April 2018 to March 2023, 11 patients affected by oligoprogressive prostate cancer were treated with SBRT targeting the nodal or bone sites of progression while maintaining the ongoing systemic therapy. Three patients were undergoing single-agent ADT (Androgen Deprivation Therapy), while the remaining eight were receiving a subsequent line of systemic therapy. All patients were evaluated with a pre-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT, which demonstrated between one and five localizations of disease. All the active sites were treated with SBRT in one (15–24 Gy) or three (21–27 Gy) fractions, except for one patient, who was treated in five fractions (35 Gy). PSA serum levels were tested at baseline, one month after RT and at least every three months; all patients underwent a post-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. The evaluated endpoints were PSA response, defined as a post-treatment decrease >50% from baseline measured within 6 months, time to next-line systemic treatment (NEST), local control (LC), biochemical progression-free survival (bPFS), radiological progression-free survival (rPFS) and freedom from polymetastatic progression (FPP). Results: Nineteen lesions were treated (seven nodal and twelve bone). At a median follow-up of 19 months (7–63), 9 of the 11 patients had a PSA response; all patients had local control of the treated metastases. A total of six patients switched to a next-line systemic treatment, with a median NEST of 13 months. Six patients had polymetastatic progression with an FPP median time of 19 months. No patients died during the follow-up period. The SBRT-related toxicity was negligible. Conclusions: Our data support the use of SBRT targeting the sites of oligoprogressive disease before moving to a subsequent line of systemic treatment in patients with metastatic prostate cancer. Prospective studies to evaluate the potential impact of this approach on overall survival are warranted.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario. Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death. We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7)or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period. We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on incomeor distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population.

278P Full-coverage radiotherapy for prostate cancer patients with oligometastases

278P Full-coverage radiotherapy for prostate cancer patients with oligometastases

Toxicity and Patient Reported Quality of Life after PSMA-PET and mpMRT-Based Focal Dose Escalated Definitive Radiotherapy in Prostate Cancer Patients: 2-Year Follow-Up of the HypoFocal Phase II Trial

The prospective, 2-armed non-randomized HypoFocal phase II trial investigates the safety and feasibility of focal dose escalated external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) patients based on PSMA-PET and multiparametric MRI. This approach improves tumor coverage and thus putatively treatment effectiveness but leads to larger boost volumes. Here we present toxicity and patient reported quality of life (QoL) results after 2 years follow-up (FU) MATERIALS/METHODS: Patients with intermediate- or high-risk PCa and cN0/cM0 stage were included. Patients in arm A received 60 Gy in 20 fractions to the prostate with an integrated boost of up to 75 Gy. Patients in arm B received one session HDR-BT with 15 Gy to the prostate and a boost of up to 19 Gy, followed by EBRT of 44 Gy in 20 fractions. Boost volumes were defined by PSMA-PET and mpMRI based on validated approaches. Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v5.0) and QoL with IPSS and EORTC questionnaires (QLQ30 and PR25) were assessed. Fifty patients were treated in both arms in two centers (Freiburg and Berlin). Table 1 shows patients characteristics. In arm, A grade 2 GU and GI toxicity rates after 2 years were 8% and 4%. There were no grade 3 GU toxicities. Two patients experienced grade 3 GI toxicities due to multifactorial causes. In Arm B grade 2 GU and GI toxicity rates after 2 years were 17% and 0%. No grade 3 toxicities were observed in arm B. Toxicities were not statistically significantly different between baseline and 2y FU (p>0.055). QoL analysis was performed with patients with available questionnaires at baseline and 2y FU (12-15 in Arm A and 13-15 in Arm B). Only bowel function (p = 0.0005, median 4 vs 25 points) in Arm A and sexual- (p = 0.016, median 25 vs 50 points) and bowel function (p = 0.004, median 0 vs 8 points) and dyspnea (p = 0.031, median 0 vs 0 points) in Arm B decreased significantly after 2 year FU. Other QoL items were not significantly different. Bowel symptoms were significantly worse in Arm A compared to Arm B (p = 0.003). Median PSA values after 2 years were 0.23 ng/ml in Arm A and 0.33 ng/ml in Arm B. Despite large boost volumes, the 2 years FU of the HypoFocal-Phase II trials shows no significantly increased GU and GU toxicities compared to baseline symptoms. Patients reported about a good QoL but increased bowel symptoms after 2 years, particularly if treated with EBRT only. Implementation of PSMA-PET into focal dose escalated radiotherapy approaches appears safe and feasible. However, radioproctitis demands careful management. The current PSA values suggest a highly effective therapy, but longer FU is needed to evaluate oncological outcomes. The HypoFocal-SBRT phase III trial will evaluate the PSMA-PET and mpMRI-based focal dose escalated SBRT.

328 Toxicities Associated with Radiotherapy for Prostate Cancer Patients Treated with VMAT

328 Toxicities Associated with Radiotherapy for Prostate Cancer Patients Treated with VMAT

Radiomics based predictive modeling of rectal toxicity in prostate cancer patients undergoing radiotherapy: CT and MRI comparison.

Rectal toxicity is one of the common side effects after radiotherapy in prostate cancer patients. Radiomics is a non-invasive and low-cost method for developing models of predicting radiation toxicity that does not have the limitations of previous methods. These models have been developed using individual patients' information and have reliable and acceptable performance. This study was conducted by evaluating the radiomic features of computed tomography (CT) and magnetic resonance (MR) images and using machine learning (ML) methods to predict radiation-induced rectal toxicity. Seventy men with pathologically confirmed prostate cancer, eligible for three-dimensional radiation therapy (3DCRT) participated in this prospective trial. Rectal wall CT and MR images were used to extract first-order, shape-based, and textural features. The least absolute shrinkage and selection operator (LASSO) was used for feature selection. Classifiers such as Random Forest (RF), Decision Tree (DT), Logistic Regression (LR), and K-Nearest Neighbors (KNN) were used to create models based on radiomic, dosimetric, and clinical data alone or in combination. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), accuracy, sensitivity, and specificity were used to assess each model's performance. The best outcomes were achieved by the radiomic features of MR images in conjunction with clinical and dosimetric data, with a mean of AUC: 0.79, accuracy: 77.75%, specificity: 82.15%, and sensitivity: 67%. This research showed that as radiomic signatures for predicting radiation-induced rectal toxicity, MR images outperform CT images.

Contour-guided deep learning based deformable image registration for dose monitoring during CBCT-guided radiotherapy of prostate cancer.

To evaluate deep learning (DL)-based deformable image registration (DIR) for dose accumulation during radiotherapy of prostate cancer patients. Data including 341 CBCTs (209 daily, 132 weekly) and 23 planning CTs from 23 patients was retrospectively analyzed. Anatomical deformation during treatment was estimated using free-form deformation (FFD) method from Elastix and DL-based VoxelMorph approaches. The VoxelMorph method was investigated using anatomical scans (VMorph_Sc) or label images (VMorph_Msk), or the combination of both (VMorph_Sc_Msk). Accumulated doses were compared with the planning dose. The DSC ranges, averaged for prostate, rectum and bladder, were 0.60-0.71, 0.67-0.79, 0.93-0.98, and 0.89-0.96 for the FFD, VMorph_Sc, VMorph_Msk, and VMorph_Sc_Msk methods, respectively. When including both anatomical and label images, VoxelMorph estimated more complex deformations resulting in heterogeneous determinant of Jacobian and higher percentage of deformation vector field (DVF) folding (up to a mean value of 1.90% in the prostate). Large differences were observed between DL-based methods regarding estimation of the accumulated dose, showing systematic overdosage and underdosage of the bladder and rectum, respectively. The difference between planned mean dose and accumulated mean dose with VMorph_Sc_Msk reached a median value of +6.3Gy for the bladder and -5.1Gy for the rectum. The estimation of the deformations using DL-based approach is feasible for male pelvic anatomy but requires the inclusion of anatomical contours to improve organ correspondence. High variability in the estimation of the accumulated dose depending on the deformable strategy suggests further investigation of DL-based techniques before clinical deployment.

PO-2047 Stereotactic radiotherapy of prostate cancer patients–two techniques comparison: preliminary results

PO-2047 Stereotactic radiotherapy of prostate cancer patients–two techniques comparison: preliminary results

The impact of the apparent diffusion coefficient for the early prediction of the treatment response after definitive radiotherapy in prostate cancer patients

PurposeWe assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients. Materials and MethodsThe clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses. ResultsWith a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10-3 mm2/sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10-3 mm2/sec was significantly lower than patients with tumor ADC > 0.96 × 10-3 mm2/sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS. ConclusionThese findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients.

Isotonic design for phase I cancer clinical trials with late-onset toxicities

ABSTRACT This article addresses the problem of identifying the maximum tolerated dose (MTD) in Phase I dose-finding clinical trials with late-onset toxicities. The main design challenge is how best to adaptively allocate study participants to tolerable doses when the evaluation window for the toxicity endpoint is long relative to the accrual rate of new participants. We propose a new design framework based on order-restricted statistical inference that addresses this challenge in sequential dose assignments. We illustrate the proposed method on real data from a Phase I trial of bortezomib in lymphoma patients and apply it to a Phase I trial of radiotherapy in prostate cancer patients. We conduct extensive simulation studies to compare our design’s operating characteristics to existing published methods. Overall, our proposed design demonstrates good performance relative to existing methods in allocating participants at and around the MTD during the study and accurately recommending the MTD at the study conclusion.

Dosimetric and Radiobiological Comparison of Three- Dimensional Conformal Radiotherapy and Helical Tomotherapy in Whole Pelvic Radiotherapy of Prostate Cancer Patients

Dosimetric and Radiobiological Comparison of Three- Dimensional Conformal Radiotherapy and Helical Tomotherapy in Whole Pelvic Radiotherapy of Prostate Cancer Patients

P056 - Diagnostic value of sentinel lymph node biopsy for nodal staging before radiotherapy in prostate cancer patients with clinically localized disease on PSMA PET/CT versus conventional imaging

P056 - Diagnostic value of sentinel lymph node biopsy for nodal staging before radiotherapy in prostate cancer patients with clinically localized disease on PSMA PET/CT versus conventional imaging

The Dosimetric Effects of Long On-Couch Time of Adaptive Ultra-Hypofractionated Radiotherapy for Prostate Cancer Patients on a 1.5 MR Linac

<h3>Purpose/Objective(s)</h3> To quantitatively characterize the dosimetric effects of long on-couch time of adaptive radiotherapy for prostate cancer patients on 1.5-T MR-Linac. <h3>Materials/Methods</h3> Seventeen patients consecutively treated with ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-T MR-Linac were recruited from an on-going prospective phase II trial (NCT05183074). UHF-RT with dose of 36.25Gy in 5 fractions to whole prostate w/o seminal vesicles (SVs) (N=12) was delivered every other day, with a boost dose of 40Gy to whole prostate (CTV4000, N=16). Except the Pre-MR for registration and re-contouring and Position Verification-MR (PV-MR) for dose/position check which were conventionally used in Adapt-To-Shape (ATS) workflow, we also collected 3D-MR during beam-on phase (Bn-MR) and after RT (Post-MR). For each fraction, the contours of targets and organs-at-risk (OARs) on PV-MR, Bn-MR and Post-MR were projected from the Pre-MR by deformable registration, and manually adapted by the physician, followed by dose-recalculation of the ATS plan. The dose parameters of target volumes and OARs on each scan were generated in a commercially available software for final analysis. <h3>Results</h3> In total, 290 MR-scans were collected, including 85 Pre-MR, 85 PV-MR, 49 Bn-MR and 71 Post-MR scans, respectively. For each fraction, the volume differences of prostate and CTV on different scans were less than 3.0cc, indicating good alignment of target contouring. With median 49 (24-78) minutes of on-couch time, the mean PTV-V95% (34.4Gy) of plans on PV-MR, Bn-MR and Post-MR was 97.69±2.03%, 97.04±2.29%, and 96.82±2.59%, respectively, compared with 99.27±0.75% of ATS plan. Furthermore, the mean CTV-V100% (36.25Gy) of plans on PV-MR, Bn-MR and Post-MR was 99.32±1.20%, 98.59±1.84% and 98.65±1.87, respectively, compared with 99.93±0.30% of ATS plan. With excellent dose coverage of prostate-V100% (36.25Gy) (99.73±0.79% on PV-MR, 99.41±1.35% on Bn-MR and 99.38±1.35% on post-MR), the main reason of lower CTV-V100% was due to mild underdose of SVs (96.97±6.26% on PV-MR, 93.62±12.94% on Bn-MR and 94.69±9.22% on post-MR). With comparison to values of ATS plan, the actual dose of rectum wall during the whole workflow also varied, with mean △V38_Gy of 0.23±0.28cc on PV-MR, 0.41±0.51cc on Bn-MR and 0.39±0.52cc on post-MR, with mean △V36_Gy of 0.27±0.57cc on PV-MR, 0.39±0.71cc on Bn-MR and 0.30±0.68cc on post-MR, respectively. However, the V29_Gy of rectum wall increased by >15% was only observed in one scan. On the contrary, no obvious increase of bladder wall dose was seen due to gradual growth of bladder over the workflow. <h3>Conclusion</h3> This dosimetry analysis demonstrated reliable dose coverage of target volumes during beam-on period with adaptive ATS workflow on 1.5-T MR-Linac. The 3 mm CTV-PTV margin applied in our study have proven to be large enough for prostate irradiation, but might be insufficient for SVs incidentally. More attention should be paid to restrict the rectum wall high dose when optimizing ATS plan.

Oral Cavity Calprotectin and Lactoferrin Levels in Relation to Radiotherapy.

Background: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. Methods: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. Results: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. Conclusions: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.

Risk of second primary malignancies associated with radiotherapy in prostate cancer patients: competing risk analysis.

Background: The effect of radiotherapy (RT) for second primary malignancies (SPMs) among prostate cancer survivors iscontroversial. Methods: Applying logistic regression, competing risk analysis and propensity score matching method, this study analyzed clinical data from the Surveillance, Epidemiology, and End Results program to compare the risk for SPMs between patients receiving RT and non-RT. Results: In this study, prostate cancer patients treated with RT developed more SPMs in the anus, bladder, rectum, liver, lung and bronchus and lymphoma than non-RT groups. Conclusion: More intensive surveillance should be adopted for these cancers among prostate cancer survivors.

Mapping of Recurrence Sites Following Adjuvant or Salvage Radiotherapy for Prostate Cancer Patients.

IntroductionAlthough salvage and adjuvant radiotherapy (RT) are effective in prostate cancer (PC) patients, 30%–40% of men will have disease progression. The objective was to describe the pattern of recurrence in PC patients with biochemical failure (BF) following postoperative RT.MethodsWe retrospectively analyzed 935 PC patients treated from 2009 to 2019 with adjuvant or salvage RT at the Institut de Cancérologie de l’Ouest. Of these, 205 (22%) developed BF of whom 166 underwent imaging. Patients with identified radiologic failure prior any specific treatment were included to determine the site of relapse categorized as local (L)-only, locoregional (LR), or metastatic (M) recurrence. Main disease characteristics and RT fields were examined in relation to sites of recurrence.ResultsOne hundred forty-one patients were identified with 244 sites of failure on imaging. Of these, 108 patients had received RT to the PB alone and 33 RT to the PB and pelvic lymph nodes (PB+PLN). Androgen-deprivation therapy was used concomitantly in 50 patients (35%). The median PSA at imaging was 1.6 ng/ml (range, 0–86.7). In all, 74 patients (52%) had M disease (44% in the PB group and 79% in the PB+PLN group), 61 (43%) had LR failure (52% in the PB alone group and 15% in the PB+PLN group), and six (4%) had L-only failure, at a median of 26.7 months (range, 5–110.3) from RT. Metastases were in extra-pelvic LN (37 (15%)), bones (66 (27%)), and visceral organs (eight (3%)). Fifty-three (48%) of the pelvic LN failures in the PB group would have been encompassed by standard PLN RT volume.ConclusionWe found that most patients evaluated for BF after postoperative RT recurred outside the RT field. Isolated pelvic nodal failure was rare in those receiving RT to the PB+PLN but accounted for half of failures in those receiving PB alone RT. Imaging directed salvage treatment could be helpful to personalize radiation therapy plan.

Grade migration and important prognostic factors in a pathology specimen for radical radiotherapy in prostate cancer patients.

The study aimed to evaluate grade migration and prognosis depending on pathologic features in patients with prostate cancer treated with radical external beam radiotherapy. The study included 139 patients with an initial Gleason score of 7 (3+4 or 4+3) i.e., Grade Group 2-3 (GG2-GG3) treated between 2008 and 2013. The clinical outcome was assessed with respect to biochemical control (BC) and biochemical disease-free survival (bDFS). After re-evaluation, the majority of patients (96 patients - 69%) were up-graded from GG2-3. Finally, there were 4 patients (3%) with grade GG1, 12 patients (9%) - GG2, 27 patients (19%) - GG3, 51 patients (37%) - GG4 and 45 patients (32%) - GG5. In 42 patients (30%) a cribriform pattern was observed. Among the analyzed factors only the GGs were important for BC (p = 0.011) and the cribriform pattern was of borderline significance (p = 0.06). The 5-year biochemical control was 100% in GG1-3 and 84% in GG4-5. The 5-year biochemical control was 81% and 93%, if cribriform or no cribriform pattern was detected, respectively. In conclusion, re-evaluation and verification of pathology specimens in accordance with contemporary rules upgraded the Gleason score in the majority of patients. The aggressive behavior of prostate cancer starts to occur from GG 4. Cribriform pattern almost tripled the biochemical failure rate.

Cranial Radiotherapy for Prostate Cancer Patients With Brain Metastases Inaccessible to Stereotactic Radiotherapy.

To evaluate patients and treatment characteristics as well as clinical outcome in patients with intracranial metastases from prostate cancer (PCA) treated with palliative radiotherapy. Fifteen patients treated for intracranial metastases of PCA were identified. The median age of patients was 69 years. 80% of patients received whole brain radiotherapy and 20% received partial brain radiotherapy. Clinical outcome was assessed. Univariate analysis was performed to analyze the impact of patient specific parameters on survival. There was no >G2 acute or any late toxicity. Median time from the first diagnosis of PCA to first diagnosis of intracranial metastases was 62 months (range=15-160 months). Median survival from first diagnosis of intracranial metastases was 14 weeks (range=0-126 weeks) and 6 weeks (range=0-47 weeks) from the start of radiotherapy. In univariate analysis, survival was significantly better for patients with an Eastern Cooperative Oncology Group (ECOG) performance status 1 compared to ECOG 2-3 [18 weeks (range=5-47 weeks) vs. 3 weeks (range=0-21 weeks), p=0.030] and Recursive Partitioning Analysis (RPA) class 2 compared to RPA class 3 [18 weeks (range=5-47 weeks) vs. 6 weeks (range=0-21 weeks), p=0.045]. Overall survival of the patients with wide-spread intracranial metastases from PCA was poor. The decision for a radiotherapy should be done on individual patient basis.

Evaluative study between calculated and measured DVHs for advance techniques of radiotherapy for Prostate Cancer Patients

Evaluative study between calculated and measured DVHs for advance techniques of radiotherapy for Prostate Cancer Patients

Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients.

Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment may help increase the response to prostate bed irradiation while minimizing potential side effects. This perspective review focuses on the most relevant molecules that may have an impact when combined with salvage radiotherapy, and underlines the strategies that need to be developed to increase the efficacy of salvage post-prostatectomy radiotherapy in prostate cancer patients.