Total body irradiation (TBI), used as part of the conditioning regimen prior to allogeneic and autologous hematopoietic cell transplantation, is the delivery of a relatively homogeneous dose of radiation to the entire body. TBI has a dual role, being cytotoxic and immunosuppressive. This allows it to eliminate disease and create “space” in the marrow while also impairing the immune system from rejecting the foreign donor cells being transplanted. Advantages that TBI may have over chemotherapy alone are that it may achieve greater tumour cytotoxicity and better tissue penetration than chemotherapy as its delivery is independent of vascular supply and physiologic barriers such as renal and hepatic function. Therefore, the so-called “sanctuary” sites such as the central nervous system (CNS), testes, and orbits or other sites with limited blood supply are not off-limits to radiation. Nevertheless, TBI is hampered by challenging logistics of administration, coordination between hematology and radiation oncology departments, increased rates of acute treatment-related morbidity and mortality along with late toxicity to other tissues. Newer technologies and a better understanding of the biology and physics of TBI has allowed the field to develop novel delivery systems which may help to deliver radiation more safely while maintaining its efficacy. However, continued research and collaboration are needed to determine the best approaches for the use of TBI in the future.

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.

Background: The ideal timing of androgen deprivation therapy (ADT) for patients with biochemical recurrence (BCR) of prostate cancer (PCa) remains controversial due to its side effects and uncertain impact on survival outcomes. Methods: We performed a review of the current literature by comprehensively searching the PubMed, Embase, and Cochrane databases to determine the optimal timing of ADT initiation after biochemical recurrence. We selected 26 studies including systematic reviews, randomized controlled trials (RCTs), and retrospective studies, while also reviewing practice guidelines. Results: Not all patients with BCR cancer experience clinical or radiological progression. While early ADT may delay progression, evidence of its effect on PCa-specific mortality remains inconclusive. The PSA thresholds for initiating ADT vary, complicating decision-making. Key predictors of progression include a short PSA doubling time (PSADT), a high Gleason score (GS), and a brief interval to BCR of PCa post-radiotherapy (RT). Combining ADT with androgen receptor pathway inhibitors (ARPIs) has been shown to improve metastasis-free survival in high-risk patients. Conclusion: The ideal timing of ADT initiation in BCR PCa remains uncertain. Early ADT can help control the progression, but its effect on PCa-specific mortality is unclear. Stratifying patients by their risk factors, such as their PSADT, GS, and time to BCR can guide individualized treatment. In high-risk patients, delaying ADT should be avoided, while combining ADT with an androgen receptor pathway inhibitor (ARPI) may further improve outcomes.

Background: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. Methods: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. Findings: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. Interpretation: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.

Purpose: To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT (LT-ADT). Materials and Methods: From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. Results: At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 μg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. Conclusions: Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.

Purpose: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). Methods: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin on day one of EBRT or the occurrence of RI-LUTSs. LUTSs were quantified using the international prostate symptom score (IPSS) at regular intervals during the study. The primary endpoint was the change in the IPSS from baseline to the last day of radiotherapy (RT). Secondary endpoints included changes in IPSS from baseline to 4 weeks and 12 weeks after the start of RT. Results: Patient demographics, baseline IPSS, and prescribed radiation doses were balanced between arms. On the last day of RT, the mean IPSS was 14.8 (SD 7.6) in the experimental arm and 15.7 (SD 8.5) in the control arm (p = 0.40). There were no significant differences in IPSSs between the study arms in the intention-to-treat (ITT) analysis at baseline, the last day of RT, and 4 and 12 weeks post-RT. Conclusion: Prophylactic α-blockers were not effective at significantly reducing RI-LUTSs in prostate cancer patients treated with EBRT. Treating patients with α-blockers at the onset of RI-LUTSs will avoid unnecessary drug exposure and toxicity.