Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy

AimThe purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients.BackgroundPrevious hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT.Materials and methodsWe evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04 Gy at 2.52 Gy/fraction (N = 25; 66%), 70 Gy at 2.5 Gy/fraction (N = 4; 11%) and 70.2 Gy at 2.6 Gy/fraction (N = 9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.ResultsMedian age at diagnosis was 70 years (range 49–80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P = 0.025). Patients with PSA ≤8 (P = 0.048) or comorbidities (P = 0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P = 0.028).ConclusionsHypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity.     

Helical tomotherapy re-irradiation for patients affected by local radiorecurrent prostate cancer

BackgroundSalvage re-irradiation in patients affected by radiorecurrent prostate cancer might be a valid as well as challenging treatment option. The aim of this study was to evaluate feasibility and toxicity of salvage external beam radiotherapy (EBRT) re-treatment in patients affected by radiorecurrent prostate cancer within the prostate gland or the prostate bed.Materials and Methods15 patients underwent EBRT re-treatment using helical tomotherapy (HT), with daily Megavolt computed tomography image-guidance. We registered toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Biochemical relapse was defined as a PSA increase > 20% compared with the pre-EBRT re-treatment value. Survival curves were calculated using the Kaplan-Meier method.ResultsAll patients received a total dose of 50 Gy (25 × 2 Gy), and 7 (46.6%) had concomitant androgen deprivation therapy (median duration of 12 months). With a median follow-up of 40.9 months, the 2-year and 4-year biochemical relapse-free survival were 55% and 35%, respectively. Acute and late genito-urinary (GU) toxicity ≥2 were recorded in 4 (26.6%) and 5 (33.3%) patients, respectively, and the 4-year late GU toxicity was 30%. Acute gastrointestinal toxicity ≥2 was recorded in 2 (13.3%) cases, whereas no patient experienced late toxicity.ConclusionsDespite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.     

Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis

BackgroundTo date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy.Materials and methods76 patients were retrospectively analyzed. A total dose of 60 Gy (20 × 3 Gy) or 67.5 Gy (25 × 2.7 Gy) was prescribed. The χ² test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis.Resultsmedian follow-up was 42.26 months [interquartile (IQR), 23–76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57–34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013).ConclusionsHT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa.     

Identifying skeletal-related events for prostate cancer patients in routinely collected hospital data

BackgroundNon-osteoporotic skeletal-related events (SREs) are clinically important markers of disease progression in prostate cancer. We developed and validated an approach to identify SREs in men with prostate cancer using routinely-collected data.MethodsPatients diagnosed with prostate cancer between January 2010 and December 2013 were identified in the National Prostate Cancer Audit, based on English cancer registry data. A coding framework was developed based on diagnostic and procedure codes in linked national administrative hospital and routinely-collected radiotherapy data to identify SREs occurring before December 2015. Two coding definitions of SREs were assessed based on whether the SRE codes were paired with a bone metastasis code (‘specific definition’) or used in isolation (‘sensitive definition’). We explored the validity of both definitions by comparing the cumulative incidence of SREs from time of diagnosis according to prostate cancer stage at diagnosis with death as a competing risk.ResultsWe identified 40,063, 25,234 and 13,968 patients diagnosed with localised, locally advanced and metastatic disease, respectively. Using the specific definition, we found that the 5-year cumulative incidence of SREs was 1.0 % in patients with localised disease, 6.0 % in patients with locally advanced disease, and 42.3 % in patients with metastatic disease. Using the sensitive definition, the corresponding cumulative incidence figures were 9.0 %, 14.9 %, and 44.4 %, respectively.ConclusionThe comparison of the cumulative incidence of SREs identified in routinely collected hospital data, based on a specific coding definition in patients diagnosed with different prostate cancer stage, supports their validity as a clinically important marker of cancer progression.     

Early closure of phase II prospective study on acute and late tolerance of hypofractionated radiotherapy in low-risk prostate cancer patients

Aim

To assess acute and late toxicity of hypofractionated radiotherapy, its efficacy and impact on quality of life in patients with low-risk prostate cancer.

Materials and methods

Since August 2006 to October 2007, 15 prostate cancer patients with favorable clinical features, aged 54–74 years (mean 67 years) entered the study. Tumor stage in the majority (73%) of patients was T2a, the mean pretreatment PSA value was 7.2 ng/ml (range 5–10.9 ng/ml). The study group was treated 3 times a week with 4 Gy per fraction to the total dose of 60 Gy within 5 weeks. 3D conformal treatment planning was used with no fiducial markers. Acute and late toxicity was evaluated using modified EORTC/RTOG/LENT scoring systems. Patients regularly filled the EORTC QLQ-PR25 questionnaires.

Results

All patients completed radiotherapy according to the plan. During radiotherapy, 26% of patients had grade 1–2 rectal symptoms. The incidence of acute urinary toxicity score was 26%, 60%, and 14% for grade 0–1, 2 and 3, respectively. One year after RT, the incidence of grade 2 GI toxicity was 27%, which was the reason for an early closure of the accrual. Grade 2 late urinary toxicity was noted in 20% of patients. The mean PSA level was 0.61 ng/ml after 24 months and 0.47 ng/ml after 36 months (range: 0.06–1.54 ng/ml).

Conclusions

Low number of patients does not allow to determine the influence of hypofractionation on unsatisfactory tolerance of this regimen. Suboptimal (from the present day''s perspective) target localization (no fiducial markers) could potentially explain higher than expected late GI reactions in our series.     

Improving outcomes in high-risk prostate cancer with radiotherapy

There have been significant improvements in the radiotherapeutic management of patients with high risk prostate cancer. Randomized trials have clearly demonstrated improved outcomes with the combination of radiotherapy in conjunction with androgen deprivation. While these trials have utilized low doses of radiotherapy in the range of 70 Gy, recent studies have suggested that significant benefits of combined androgen deprivation therapy with dose escalated radiotherapy are also observed. The use of high radiation dose levels in the setting of high risk prostate cancer is important, and strategies which combine external beam radiotherapy with a brachytherapy boost may provide an opportunity for even greater intensification of the radiation dose to the prostate target. Systemic therapies, second generation anti-androgen therapy and novel targeted agents integrated with radiotherapy will open up new vistas and challenges for further improved outcomes in patients with high-risk disease.     

Stereotactic ablative radiotherapy for oligometastatic prostate cancer

BackgroundThe present study assessed clinical outcomes of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer patients.Materials and methodsBetween 2017 and 2020, 37 lesions (12 osseous and 25 nodal targets) detected with conventional and/or functional imaging, were treated in 29 patients (pts), in different clinical settings: de novo oligometastatic (2 pts), oligorecurrent castration-sensitive (19 pts), castration-resistant (6 pts) prostate cancers and oligoprogressive disease during systemic therapy (2 pts). SBRT was delivered with volumetric modulated arc therapy up to a total dose of 21 Gy given in 3 fractions for bone and 30 Gy in 5 fractions for nodal metastases. A total of 34% of pts received hormonal therapy. We evaluated biochemical control [prostate serum antigen (PSA) increase < 10%)], progression free-survival (PFS) (time from SBRT to biochemical progression), local control (LC) (time from SBRT to in-field radiologic progression), hormone/systemic therapy-free survival, acute and late toxicities.ResultsAt 3 months, biochemical response was observed in 20/29 pts (69%). At a median follow-up of 17 months (range 6–33), 8/20 (40%) of the 3-month responders remained free from progression. Two-year PFS and LC were 37% and 70%, respectively. In-field progression occurred in 3/37 (8%) lesions. Hormone/systemic therapy was delayed by an average of 11.6 months (range 3–28). No significant difference in PFS based on the type of lesion or concomitant endocrine therapy was observed and no toxicity > grade 2 was reported.ConclusionsSBRT for oligometastatic prostate cancer offers a good biochemical/local control and tangible delay of hormone/systemic therapy without major toxicities.     

Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer

Background/aim(s)To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT).Materials/MethodsRetrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24–36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26–267).ResultsSixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8–8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7–2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6–9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26–12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33–3.79).ConclusionA positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.     

Tissue proteomics studies in the investigation of prostate cancer

Introduction: Prostate cancer (PCa) is one of the leading causes of death in the male population worldwide. Various clinical samples such as urine, blood serum, and prostatic fluid have been commonly used for the identification of PCa-associated molecular changes. Tissue, the site of oncogenesis, is increasingly gaining more attention as a study material for studies aimed at the discovery of biomarkers for predicting the disease outcome and therapeutic targets.

Areas covered: This review is the output of a systematic literature search on PubMed to retrieve articles relevant to the proteomic analysis of tissues for the study of PCa. Studies performed during the last 10 years using human tissues are summarized.

Expert commentary: Multiple proteomics studies were performed in the past 10 years focusing on PCa initial diagnosis and staging. Even though some reproducible findings have been reported, many studies lacked adequate validation of findings and relied on relatively lower-resolution proteomics techniques compared to the current state of the art. Incorporation of high-resolution proteomics techniques, including investigations of protein post-translational modifications (PTMs), is expected in the near future to complement other -omics and enhance current efforts toward the molecular subtyping of PCa for patient stratification.     

Finding safe dose-volume constraints for re-irradiation with SBRT of patients with prostate cancer relapse: The IEO experience

AimThe primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT).MethodsData from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated.ResultsTwenty-six patients were included. Median age at re-irradiation was 75 years, mean interval between the two RT courses was 5.6 years and the median follow-up was 47.7 months (13.4–114.3 months). After re-irradiation, acute and late G ≥ 2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G ≥ 2 GI events were reported in 4 (15%) patients. No acute G ≥ 2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments < 131 Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p = 0.145). Cumulative re-irradiation constraints that appear to be safe are D_30% < 57.9 Gy for bladder and D_30% < 66.0 Gy, D_60% < 38.0 Gy and V_{122.1 Gy} < 5% for rectum.ConclusionPreliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.     

Impact of rotational errors of whole pelvis on the dose of prostate-based image-guided radiotherapy to pelvic lymph nodes and small bowel in high-risk prostate cancer

BackgroundThe target volume increases when the prostate and pelvic lymph nodes (PLNs) are combined, and the fiducial markers (FMs) are placed at the edge of the irradiation field. Thus, the position of FMs may be changed by the rotational errors (REs) of “whole pelvis”. The aim of this study was to examine the impact of REs of “whole pelvis” on the dose of FMs-based image-guided radiotherapy to the PLNs and the small bowel in prostate cancer including the PLNs.Materials and methodsWe retrospectively evaluated 10 patients who underwent prostate cancer radiotherapy involving the PLNs. The position of FMs was calculated from the radiographs obtained before and after the 6D correction of pelvic REs. We simulated the delivery dose considering the daily pelvic REs and calculated the difference from the planned dose in the D_98% of the PLN clinical target volume and the D_2cc, and V_45Gy of the small bowel.ResultThe position of FMs strongly correlated with the pelvic REs in the pitch direction (r = 0.7788). However, the mean delivered doses to PLNs for 10 patients were not significantly different from the planned doses (p = 0.625). Although the D_2cc and V_45Gy of the small bowel strongly correlated with the pitch rotation of the pelvis, there was no significant difference between the delivered and planned doses (p = 0.922 and p = 0.232, respectively).ConclusionThe dosimetric effect of pelvic REs on the dose to PLNs and the small bowel was negligible during the treatment course.     

Impact of COVID-19 on the curative treatment of prostate cancer: a national cross-sectional study

BackgroundCOVID-19 pandemic affected access to cancer treatment worldwide. However, there is a lack of data about the impact in developing countries. The objective was to evaluate COVID-19 impact on curative prostate cancer (Pca) treatment in Brazil.Materials and methodsWith data extracted from the Brazilian Ministry of Health database, the Non-COVID and COVID periods were analyzed to compare the absolute number of radical prostatectomy (RP) and radiotherapy (RT) executed in the country and regions.ResultsWith data from 50,169 Pca patients (Non-COVID = 28,106 cases and COVID = 22,063) treated with RP or RT in Brazil, a significant decline in patients receiving RT or RP (−6.043 cases; p = 0.0001) was detected. Both treatment procedures (RT or PR) were reduced in all five Brazilian regions comparing the Non-COVID and COVID periods. Overall, there was a reduction on RP and RT procedures in 92% (24/25) and 76% (19/25) of the evaluated states, respectively. Comparing the variation of RT and RP per state between COVID and Non-COVID period, there is a significant difference (−18.6% vs. −29%, p = 0.03) with a higher negative impact on the RP group. The RT and RP variation had no significant relationship with the incidence of COVID cases in the states. Limitations include the non-evaluation of treatment combinations, the impact of hypofractionated radiotherapy, and other factors influencing the treatment choice.ConclusionsDuring the COVID-19 pandemic, the curative treatment with RP and RT of Pca was abruptly limited and affected. However, the number of RP was more impacted than RT during the COVID period.     

Phase I dose escalation trial of stereotactic radiotherapy prior to robotic prostatectomy in high risk prostate cancer

BackgroundThe aim of the study was to investigate the safety of combining preoperative stereotactic body radiotherapy (SBRT) with robotic radical prostatectomy (RP) for high risk prostate cancer (HRCaP). Many patients with HRCaP will require adjuvant or salvage radiotherapy after RP. The addition of preoperative SBRT before RP may spare patients from subsequent prolonged courses of RT.Materials and methodsEligible patients had NCC N HRCaP and received a total of 25 Gy or 30 Gy in five daily fractions of SBRT to the prostate and seminal vesicles followed by robotic RP with pelvic lymphadenectomy 31–45 days later. The primary endpoint was prevalence of acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints were patient-reported quality of life (QOL) and biochemical recurrence (BcR).ResultsThree patients received preoperative SBRT to 25 Gy and four received 30 Gy. Median follow-up was 18 months. Highest toxicity was grade 2 and 3 in six (85.7%) and one (14.3%) patients, respectively. All patients developed grade 2 erectile dysfunction and 4 of 7 (57%) developed grade 2 urinary incontinence (UI) within a month after surgery. One patient developed acute grade 3 UI, but there was no grade ≥ 4 toxicity. One patient experienced acute grade 2 hemorrhoidal bleeding. On QOL, acute GU complaints were common and peaked within 3 months. Bowel symptoms were mild. Two patients with pN+ experienced BcR.ConclusionsPreoperative SBRT before robotic RP in HRCaP is feasible and safe. The severity of acute GU toxicity with preoperative SBRT may be worse than RP alone, while bowel toxicity was mild.     

Long term results of HDR brachytherapy in men older than 75 with localized carcinoma of the prostate

Background

Prostate cancer is an illness with a high incidence, especially among older men. The choice of a treatment option among men above 75 years is, however, not clear. Radical prostatectomy in this age group is connected with a relatively high morbidity. A further possibility of curative treatment is radiotherapy which can be administered in the form of external beam or in combination with high dose rate (HDR) brachytherapy.

Aim

The aim of our work was to evaluate how HDR brachytherapy is tolerated among men older than 75 and how associated diseases can influence the tolerance to this treatment. Of interest to us were the treatment results and mortality from other diseases.

Materials and methods

We analyzed a sample of 20 men above 75 years old (median 77 years) who were undergoing treatment by a combination of external radiotherapy and brachytherapy. Sixteen (80%) of them had prostate cancer with an intermediate and high risk of recurrence, four had low risk prostate cancer. Most patients, 14 (70%), had less than two comorbidities.

Results

The median observation period was 57 months. No perioperative complications were recorded. Acute genitourinary toxicity (GU) to a maximum grade of 1–2 manifested in 60% of cases. Acute gastrointestinal toxicity (GIT) was observed only at grade 1 and in 25% of cases. Late GU toxicity occurred in 35% of patients, with only one showing grade 3; late GIT toxicity was recorded at grade 1 only in 3 patients (15%). 70% of the men lived longer than 3 years after treatment, at present, 50% lived more than 5 years. Long-term biochemical remission was achieved in 18 patients (90%).

Conclusions

HDR BRT is possible and well-tolerated in older men above 75 years in good condition and without serious intercurrence.Well-selected older patients with higher-risk tumours and without serious comorbidities undoubtedly benefit from radical treatment when compared with watchful waiting.     

Shrinkage of the non-malignant prostate gland volume after receiving incidental radiotherapy for rectal cancer

BackgroundThe purpose of this study was to assess the impact of coincidental radiotherapy on the volume of the non-malignant prostate gland in rectal cancer patients treated with neo-adjuvant radiotherapy.Materials and methodsIn this retrospective analysis, thirty male patients with rectal cancer who had neoadjuvant radiotherapy met the inclusion criteria. These patients had pre-treatment magnetic resonance imaging (MRI) and at least one post-treatment MRI of the pelvis and the whole of their prostate volume received the full prescribed radiotherapy dose; 45 Gy in 25 fractions (n = 22), 45 Gy in 20 fractions (n = 4) and 25 Gy in 5 fractions (n = 4).ResultsThe median age of this patient cohort was 66 years (range: 30–87). With a median interval between pre-treatment MRI and first MRI post-treatment of 2 months (range: 1–11), the mean prostate volume reduced from 36.1 cm³ [standard deviation (SD) 14.2] pre-radiotherapy to 31.3 cm³ (SD 13.0) post radiotherapy and this difference was significant (p = 0.0004).ConclusionRadiotherapy may cause shrinkage in volume of normal (non-malignant) prostate. Further research is required in this field, since these results may be of some comfort to men contemplating the consequences of radiotherapy on their quality of life. The authors suggest recording flow-rate and international prostate symptom score (IPSS) during rectal radiotherapy as a next step.     

Conversion of the helical tomotherapy plans to the step-and-shoot IMRT plans for patients with hip prosthesis during radiotherapy for prostate cancer

PurposeTo evaluate the SharePlan software in conversion of helical tomotherapy (HT) to a step and shoot IMRT (sIMRT) for patients with high-risk prostate cancer and hip prosthesis.MethodsAnalysis was performed for 16 consecutive patients treated on HT. The HT plans were converted to sIMRT plans. 3DCRT, sliding window IMRT (dIMRT) and VMAT plans for a c-arm linear accelerator (CLA) were created manually. The doses in planning target volume (PTV), bladder, rectum, bowels, femoral heads and hip prosthesis were compared using: (i) a qualitative analysis of doses in averaged dose–volume histograms, (ii) a quantitative, ranking procedure performed for each patient separately, and (iii) statistical testing based on the Friedman ANOVA and Nemenyi method.ResultsFor the bladder, rectum, and femoral head, the best dose distributions were observed for HT and sIMRT and then for dIMRT, VMAT, and finally for 3DCRT (p-values were, respectively, 0.002, 0.004 and p = 0.024). For the bowels, 3DCRT was significantly different from the rest of the techniques (p = 0.009). For the hip prosthesis, the differences were only between 3DCRT and HT/sIMRT (p = 0.038).ConclusionThe SharePlan is an efficient tool for the conversion of HT plans for patients with prostate cancer and hip prosthesis. Dose distributions in sIMRT and in HT plans are similar and are generally better than in CLA plans.     

Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma

This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b–T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b–T3 disease.