Search

Simple Summary: The role of restaging before salvage radiotherapy (sRT) for prostate cancer is still controversial. The aim of the present retrospective study was to investigate the predictive value of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) findings, including the volume and the subsite of the presumed local failure. We found that DCE-MRI at restaging for biochemical failure after radical prostatectomy seems to provide both predictive and therapeutic information. Patients with small lesions at the vesico-urethral anastomosis have an excellent prognosis after sRT. Background: To investigate the predictive role of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) findings before salvage radiotherapy after radical prostatectomy (RP). Methods: This retrospective study selected patients with biochemical failure (BF) after RP restaged with DCE-MRI. Patients underwent sRT in 30 fractions delivering 66–69 Gy and 73.5 Gy to the prostatic fossa and to the local failure as per DCE-MRI, respectively. Pelvic nodes were treated to 54 Gy in selected patients. The endpoint was BF after sRT. Results: In total, 236 patients were analyzed and 146 (61.9%) had presumed local failure at DCE-MRI: 54.8%, 23.8% and 21.4% were found at the vesico-urethral anastomosis (VUA), the bladder neck and the retro-vesical space, respectively. The presence of a local failure at DCE-MRI halved the risk of BF; VUA-only location and lesion volume were independently correlated with survival without evidence of biochemical failure (bNED) at multivariable analysis. For patients with VUA-only disease up to 0.4 cc, the 4-year-bNED was 94.6% (95%CI: 80.2–98.6%) as opposed to 80.9% (95%CI: 71.6–87.4%) and 73.7% (95%CI: 63.1–81.8%) for other lesions and no macrodisease, respectively. Conclusions: DCE-MRI at restaging for BF after RP provides predictive and therapeutic information. Patients with small lesions at the VUA have an excellent prognosis after sRT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Aim To identify factors influencing toxicity in patients affected by localized prostate cancer treated with conformal image-guided radiotherapy. Background Image guidance in combination with conformal techniques is the standard of care in localized prostate cancer, but factors affecting toxicity are still under investigation. Materials and methods 294 patients were analyzed. Median age at diagnosis was 71 year. 76 Gy (38 × 2 Gy) were delivered to the target volume. We used the χ 2 test to analyse associations between toxicity and dosimetric and clinical parameters. Multivariate analysis was performed using binary logistic regression. Kaplan–Meier method was used for survival analysis. Results Median follow-up was 62.9 months. Acute grade ≥2 gastro-intestinal toxicity (GI) was 12.1%. Acute genito-urinary (GU) toxicity of grade ≥2 was 33.9%. Actuarial 4 and 5 years late grade ≥2 GI was 3% and 4%, respectively. Four and 5-year late grade ≥2 GU toxicity was 6% and 10%. At multivariate analysis for acute toxicity rectal V 70 was correlated with GI toxicity (p = 0.01, HR 2.73 CI 1.19–6.26), and smoking habit with GU toxicity (p < 0.01, HR 2.50 CI 1.51–4.14). For late toxicity, rectal V 70 was correlated with gastro-intestinal toxicity (p = 0.04, HR 4.76 CI 1.07–21.13), and pre-radiotherapy urinary symptoms with genito-urinary toxicity (p = 0.01, HR 2.84 CI 1.29–6.22). Discussion Conformal image-guided radiotherapy shows low rates of toxicity. Smoking should be avoided during radiotherapy. Besides the evaluation of high doses received by the organs at risk, individual factors, such as co-morbidities and lifestyle choices, have an impact on normal-tissue complication risk. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of PET/CT with two novel tracers was investigated in prostate cancer patients with both a biochemical failure after surgery and a presumed local failure at multiparametric MR. Overall, both PET tracers detected only about 50% of local failures. Therefore, multiparametric MR remains the exam of choice to investigate the prostatic fossa in patients who fail surgery. Background: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). Methods: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP; subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater); a presumed local failure at mpMR; no distant metastases at 18F-fluorocholine PET/CT (CH/PET); no previous history of androgen deprivation therapy. Patients were offered both 64CuCl2 PET/CT (CU/PET) and 64Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. Results: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9–100%), DRs were 47.2% (95%CI: 36.1–58.6%) and 54.4% (95%CI: 42.7–65.7%) for CU/PET and PSMA/PET, respectively (p < 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. Conclusions: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]