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Purpose: Erectile dysfunction (ED) is a common side effect after prostate cancer stereotactic body radiation therapy (SBRT). We aimed to assess the correlation between the dose to the penile bulb (PB), internal pudendal arteries (IPA), and crura with the development of ED after ultrahypofractionation as part of a phase 2 clinical trial of urethra-sparing prostate SBRT., Methods and Materials: Among the 170 patients with localized prostate cancer from 9 centers included in the trial, 90 men with Common Terminology Criteria for Adverse Events version 4.03 grade 0 to 1 ED (ED-) at baseline treated with 36.25 Gy in 5 fractions were selected for the present analysis. Doses delivered to the PB, crura, and IPA were analyzed and correlated with grade 2 to 3 ED (ED+) development. The effect on quality of life, assessed by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-PR25) questionnaire, was reported., Results: After a median follow-up of 6.5 years, 43% (n = 39) of the patients developed ED+, and 57% (n = 51) remained ED-. The dose delivered to the crura was significantly higher in ED+ patients than in ED- patients (7.7 vs 3.6 Gy [P = .014] for the D mean and 18.5 vs 7.2 Gy [P = .015] for the D 2% , respectively). No statistically significant difference between ED+ and ED- patients was observed for the dose delivered to the PB and IPA. The median ED+-free survival was worse in patients receiving a crura D mean ≥ 4.7 versus < 4.7 Gy (51.5% vs 71.7%, P = .005) and a crura D 2% > 12 versus ≤ 12 Gy (54.9% vs 68.9%, P = .015). No ED+-free survival differences were observed for doses delivered to the PB and IPA. Decline in EORTC QLQ-PR25 sexual functioning was significantly more pronounced in patients with higher doses to the crura., Conclusions: By keeping a D mean and D 2% to crura below 4.7 and 12 Gy, respectively, the risk of developing ED+ after prostate SBRT may be significantly reduced., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series., Materials and Methods: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type., Results: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively., Conclusion: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials., (© 2024. The Author(s).)

The impact of radiotherapy (RT) on immune cell status in prostate cancer (PCa) is only partially determined. The aim of this study was to assess the effect of different RT strategies on peripheral B, T, and Natural killer (NK) lymphocytes at precise longitudinal time-points in PCa. 18 patients treated with stereotactic body radiation therapy (SBRT) (40 Gy/3FRX), definitive moderate-hypofractionation (62 Gy/20FRX), or post-operative conventional-fractionation RT (66-69 Gy/30FRX) were prospectively evaluated for the immune cell profile in terms of immune cell composition, differentiation stage, cytokine production and inhibitory receptor (IR) expression. The immune-monitoring of the 18 patients revealed that RT affects the balance of systemic immune cells, with the main differences observed between SBRT and conventionally fractionated RT. SBRT favorably impacts immune response in term of increased B cells, central-memory and effector-memory CD8 + T cells, along with decreased Treg cells after treatment. On the contrary, conventional fractionated RT had a long-term negative effect on the systemic immune profile, including a decrease of total lymphocyte counts accompanied by an increase of neutrophils-to-lymphocytes ratio. Total B and T cells decreased and Treg-to-CD8 + ratio increased. Functionality of T lymphocytes were not affected by any of the 3-fractionation schedules. Interestingly, SBRT significantly up-regulates the expression of V-domain immunoglobulin suppressor of T-cell activation (VISTA) in CD8 + T cells in the absence of other IRs. Our results indicate the relevance of systematic immunomonitoring during RT to identify novel immune-related target to design trials of combined radio-immunotherapy as a promising strategy in the clinical management of PCa., Competing Interests: The authors report there are no competing interests to declare, (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Aims: 68 Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported., Results: 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003)., Conclusions: PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging.

Purpose: Our purpose was to assess the ability of electromagnetic transponders (EMTs) to localize and track movements in patients with prostate cancer (PCa) with metallic hip prostheses (MHPs) treated with curative radiation therapy (RT)., Methods and Materials: Data sets of 8 PCa patients with MHPs (3 bilateral and 5 unilateral) treated between 2016 and 2018 with RT and EMT tracking were retrospectively assessed. The distances between the 3 EMTs (apex to left, left to right, right to apex) and the isocenter were calculated both on planning computed tomography (CT) and cone beam CT (CBCT) at the first treatment fraction and compared with data reported by Calypso. EMT position and treatment interruptions triggered by Calypso were analyzed for all evaluable treatment fractions (n = 120). Localization accuracy was quantified by recording the geometric residual value (expected limit ≤0.2 cm) at the RT setup., Results: The Calypso system was able to localize and track prostate position without any detectable interference from MHP. For every treatment fraction, the agreement between the CBCT images and Calypso guidance was optimal, with EMTs always within the defined tolerance (ie, CT-Calypso or CBCT-Calypso measured differences in inter-EMT distances within 0.3 cm). EMT to isocenter distances measured by Calypso reproduced CT data and were confirmed on CBCT scans. During RT, the EMT centroid exceeded the threshold 24 times (20% of all fractions): 5 times in the left-right, 15 times in the anteroposterior, and 4 times in the superoinferior directions. The largest motions recorded were in the anteroposterior axis: 0.6 cm anteriorly and 0.5 cm posteriorly in patients with unilateral and bilateral MHP, respectively., Conclusions: Our study represents the first clinical experience assessing the localization and tracking accuracy of Calypso EMTs during curative RT of patients with PCa with unilateral or bilateral MHP., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Radiotherapy is an emerging treatment strategy for nodal oligorecurrent prostate cancer (PCa) patients. However, large heterogeneities exist in the RT regimens used, with series reporting the use of elective nodal radiotherapy (ENRT) strategies and others the delivery of focal treatments to the relapsing nodes with Stereotactic Body Radiotherapy (SBRT). In this systematic review of the literature we compared the oncological outcomes and toxicity of the different RT regimens for nodal oligorecurrent PCa patients, with the aim of defining the optimal RT target volume in this setting., Methods: We performed a systemic search on the Pubmed database to identify articles reporting on the use of ENRT or SBRT for oligometastatic PCa with nodal recurrence., Results: Twenty-two articles were analyzed, including four prospective phase II trials (3 with SBRT and 1 with ENRT). Focal SBRT, delivered with an involved node, involved site, and involved field modality, was the most commonly used strategy with 2-year progression-free survival (PFS) rates ranging from 16 to 58% and a very low toxicity profile. Improved PFS rates were observed with ENRT strategies (52-80% at 3 years) compared to focal SBRT, despite a slightly higher toxicity rate. One ongoing randomized phase II trial is comparing both modalities in patients with nodal oligorecurrent PCa., Conclusions: With a large variability in patterns of practice, the optimal RT strategy remains to be determined in the setting of nodal oligorecurrent PCa. Ongoing randomized trials and advances in translational research will help to shed light on the best management for these patients. .

Context: Different nonsurgical therapeutic strategies can be adopted for intraprostatic relapse of prostate cancer after primary radiotherapy, including re-irradiation (with brachytherapy [BT] or external beam radiotherapy [EBRT]), high-intensity focused ultrasound (HIFU), and cryotherapy. The main issues to consider when choosing nonsurgical salvage local therapies are local tumor control and significant genitourinary toxicity., Objective: To conduct a systematic review and meta-analysis of the role of nonsurgical salvage modalities in patients with radiorecurrent prostate cancer and associated clinical outcomes and toxicity profiles., Evidence Acquisition: We performed a critical review of the Medline, Scopus, and ClinicalKey databases from January 1, 2000 through February 1, 2018 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool for case-series studies., Evidence Synthesis: A total of 64 case-series studies were included, corresponding to a cohort of 5585 patients. The modified Delphi checklist evidenced high methodological quality overall (mean quality score of 80.6%). Biochemical control rates were lowest for patients treated with HIFU (58%, 95% confidence interval [CI] 47-68%) and highest for patients treated with BT (69%, 95% CI 62-76%) and EBRT (69%, 95% CI 53-83%). The lowest prevalence of incontinence was for patients treated with BT (3%, 95% CI 0-6%; I 2 =63.4%) and the highest was among patients treated with HIFU (28%, 95% CI 19-38%; I 2 =89.7%)., Conclusions: Nonsurgical therapeutic options, especially BT, showed good outcomes in terms of biochemical control and tolerability in the local recurrence setting., Patient Summary: The current analysis demonstrated that nonsurgical salvage local therapies offer a chance of a curative local approach in radiorecurrent prostate cancer. However, high-quality data from prospective trials are needed to validate long-term outcomes from nonsurgical strategies for the treatment of intraprostatic recurrence after previous radiotherapy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The ONE SHOT trial is the first phase I/II prospective, multicenter, single-arm study assessing the efficacy and safety of a single-dose SBRT for men with localized prostate cancer. Aim of this paper is to present the phase I results of a 19 Gy single fraction urethra-sparing SBRT with real-time electromagnetic tracking., (Copyright © 2019 Elsevier B.V. All rights reserved.)