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Background: The relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown., Objective: To perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT., Design, Setting, and Participants: An NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11862 patients. Patients received one of the six permutations of low-dose RT (64 to <74 Gy) ± STADT or LTADT, high-dose RT (≥74 Gy), or high-dose RT ± STADT or LTADT., Outcome Measurements and Statistical Analyses: Metastasis-free survival (MFS) was the primary endpoint. Frequentist and Bayesian NMAs were performed to rank the various treatment strategies by MFS and biochemical recurrence-free survival (BCRFS)., Results and Limitations: Median follow-up was 8.8 yr (interquartile range 5.7-11.5). The greatest relative improvement in outcomes was seen for addition of LTADT, irrespective of RT dose, followed by addition of STADT, irrespective of RT dose. RT dose escalation did not improve MFS either in the absence of ADT (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.80-1.18) or with STADT (HR 0.99, 95% CI 0.8-1.23) or LTADT (HR 0.94, 95% CI 0.65-1.37). According to P-score ranking and rankogram analysis, high-dose RT + LTADT was the optimal treatment strategy for both BCRFS and longer-term outcomes., Conclusions: Conventionally escalated RT up to 79.2 Gy, alone or in the presence of ADT, does not improve MFS, while addition of STADT or LTADT to RT alone, regardless of RT dose, consistently improves MFS. RT dose escalation does provide a high probability of improving BCRFS and, provided it can be delivered without compromising quality of life, may represent the optimal treatment strategy when used in conjunction with ADT., Patient Summary: Using a higher radiotherapy dose when treating prostate cancer does not reduce the chance of developing metastases or death, but it does reduce the chance of having a rise in prostate-specific antigen (PSA) signifying recurrence of cancer. Androgen deprivation therapy improves all outcomes. A safe increase in radiotherapy dose in conjunction with androgen deprivation therapy may be the optimal treatment., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Simple Summary: Prostate cancer is the second most common cancer among males and is a significant cause of morbidity and mortality. The chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) are expressed in prostate cancer but their prognostic value is unclear. This study investigated CCL2 and CCR2 as prognostic biomarkers in locally advanced prostate cancer using the large TROG 03.04 RADAR clinical trial cohort. The results demonstrate that despite being expressed in prostate tumours, CCR2 and CCL2 have no prognostic value in the disease. This study investigated the prognostic value of the chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) expression in locally advanced prostate cancer treated with radiotherapy and androgen deprivation using the 10-year outcome data from the TROG 03.04 RADAR clinical trial. CCL2 and CCR2 protein expression in prostate cancer biopsies at the time of diagnosis were quantified by immunohistochemistry and digital quantification. CCR2 protein expression was detected in prostate cancer cells and was associated with prostate-specific antigen serum concentration (p = 0.045). However, neither CCL2 nor CCR2 tissue expression could predict prostate cancer progression, or other clinicopathological parameters including perineural invasion and patient outcome. In serum samples, CCL2 concentration at the time of diagnosis, as assayed by enzyme-linked immunosorbent assay, was significantly higher in patients with prostate cancer compared with benign prostatic hyperplasia (median difference 0.22 ng/mL, 95% CI, 0.17–0.30) (p < 0.0001) and normal controls (median difference 0.13 ng/mL, 95% CI, 0.13–0.17) (p < 0.0001). However, circulating CCL2 was not statistically significant as a predictor of disease progression and patient outcome. In conclusion, this study shows that although CCL2 and CCR2 are expressed in prostate cancer, with an increased level of CCL2 in the serum, neither CCL2 nor CCR2 expression has a clinical prognostic value in locally advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Introduction: Quality assurance methods are incorporated into multicentre radiotherapy clinical trials for ensuring consistent application of trial protocol and quantifying treatment uncertainties. The study's purpose was to determine whether post-treatment disease progression is associated with measures of the quality of radiotherapy treatment.Methods: The TROG 03.04 RADAR trial tested the impact of androgen deprivation on prostate cancer patients receiving dose-escalated external beam radiation therapy. The trial incorporated a plan-review process and Level III dosimetric intercomparison at each centre, from which variables suggestive of treatment quality were collected. Kaplan-Meier statistics and Fine and Gray competing risk modelling were employed to test for associations between quality-related variables and the participant outcome local composite progression.Results: Increased 'dose-difference' at the prostatic apex and at the anterior rectal wall, between planned and measured dose, was associated with reduced progression. Participants whose treatment plans included clinical target volume (CTV) to planning target volume (PTV) margins exceeding protocol requirements also experienced reduced progression. Other quality-related variables, including total accrual from participating centres, measures of target coverage and other variations from protocol, were not significantly associated with progression.Conclusions: This analysis has revealed the association of several treatment quality factors with disease progression. Increased dose and dose margin coverage in the prostate region can reduce disease progression. Extensive and rigorous monitoring has helped to maximise treatment quality, reducing the incidence of quality-indicator outliers, and thus reduce the chance of observing significant associations with progression rates. [ABSTRACT FROM AUTHOR]

Background It remains unclear whether eradication of oligometastases by stereotactic body radiation therapy or other means will result in cure or prolongation of survival in some cases, or merely provide palliation. We address this issue with prospectively collected progression and treatment data from the TROG 03.04 RADAR randomised controlled trial for men with locally advanced prostate cancer (PC). Methods Three Fine and Gray competing risk survival models with time-dependent covariates were used to determine whether metastatic progression status at first diagnosis of bony metastases, i.e. number of bony sites involved and presence of prior or simultaneous other sites of progression, impacts on prostate cancer-specific mortality (PCSM) when adjusted for baseline prognostic factors and allocated primary treatment. Results Between 2003 and 2014, 176 of the 1071 subjects developed bone metastases, 152 developed other sites of progression and 91 died of PC. All subjects received secondary treatment using androgen suppression but none received extirpative treatments. The three models found evidence: 1 – of a clear prognostic gradient according to number of bony metastatic sites; 2 – that other sites of progression contributed to PCSM to a lesser extent than bone progression; and 3 – that further bony metastatic progression in men with up to 3 bony metastases had a major impact on PCSM. Conclusion Randomised trials are essential to determine the value of extirpative treatment for oligometastatic bony metastases due to PC. [ABSTRACT FROM AUTHOR]

The article focuses on measuring personal and functional changes in survivors of prostate cancer (PCa). Topics include treatments for PCa such as prostatectomy, radiation therapy, and hormone therapy; measurement of symptomatic side effects in prostate cancer survivors using the National Comprehensive Cancer Network's Distress Thermometer Screening Tool and other tools; and development and evaluation of a scale for measuring symptoms and resulting anxiety and depression.

Abstract: Purpose: In the TROG 96.01 trial 6month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared to RT alone, but 3months did not. We ask why? Methods: Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0month NAS) to 66Gy, 3months or 6months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology. Results: In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6month NAS, respectively. Compared with 0month, significant reductions in PSA doubling time in subjects with DP occurred following 3month NAS (p =0.01), but a significant reduction (p =0.01) and a near significant delay in DPs (p =0.06) occurred after 6month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4years. Conclusions: The data are consistent with the failure of 3month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment. [Copyright &y& Elsevier]

Summary: Background: The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results. Methods: Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5–7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. Findings: 802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9–11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57–0·90; p=0·003) and local progression (0·49, 0·33–0·73; p=0·0005), and improved event-free survival (0·63, 0·52–0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46–0·72; p<0·0001) and local progression (0·45, 0·30–0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42–0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60–1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60–1·23; p=0·398), or all-cause mortality (0·84, 0·65–1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31–0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32–0·74; p=0·0008), and all-cause mortality (0·63, 0·48–0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation. Interpretation: 6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation. Funding: Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough. [Copyright &y& Elsevier]

The article provides information on a study which compared short and long-term androgen suppression plus external beam radiation therapy in the treatment of high-risk prostate cancer. The study assessed whether an association exists between length of survival after randomization and duration of androgen suppression therapy (AST) administered from a pooled analysis of men participants. The materials and methods used in the study are discussed, which include information on study cohort, staging and treatment. Statistical methods used are outlined, as well.

Summary: Background: Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer. Methods: 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6·5–7·0 weeks to the prostate and seminal vesicles); 3 months'' androgen deprivation with 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months'' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat. Findings: 802 (98%) patients were eligible for analysis. Median follow-up was 5·9 years (range 0·1–8·5). Compared with patients assigned no androgen deprivation, those assigned 3 months'' treatment had significantly improved local failure (hazard ratio [HR] 0·56 [95% CI 0·39–0·79], p=0·001), biochemical failure-free survival (0·70 [0·56–0·88], p=0·002), disease-free survival (0·65 [0·52–0·80], p=0·0001), and freedom from salvage treatment (0·73 [0·56–0·96], p=0·025). 6 months'' androgen deprivation significantly improved local failure (0·42 [0·28–0·62], p<0·0001), biochemical failure-free survival (0·58 [0·46–0·74], p<0·0001), disease-free survival (0·56 [0·45–0·69], p<0·0001), freedom from salvage treatment (0·53 [0·40–0·71], p<0·0001), distant failure (0·67 [0·45–0·99], p=0·046) and prostate-cancer-specific survival (0·56 [0·32–0·98], p=0·04) compared with no androgen deprivation. Interpretation: 6 months'' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit. [Copyright &y& Elsevier]

Adding high-dose-rate brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical control but may affect patient-reported quality of life (QOL). We sought to determine long-term QOL outcomes for EBRT+BT versus EBRT alone. This was a post hoc analysis of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (TROG 03.04 RADAR) trial. Only patients who received 74 Gy conventionally fractionated EBRT (n = 260) or 46 Gy conventionally fractionated EBRT plus 19.5 Gy in 3 fractions high-dose-rate BT boost (n = 237) were included in this analysis. The primary endpoint was patient-reported QOL measured using the European Organisation for Research and Treatment of Cancer QOL (EORTC QLQ-C30) and prostate-specific QOL module (EORTC QLQ-PR25) questionnaires. We evaluated temporal changes in QOL scores, rates of symptom resolution, and the proportion of men who had decrements from baseline of >2 × the threshold for minimal clinically important change (2 × MCIC) for each domain. At 5, 17, and 29 months after radiation therapy, the EBRT+BT group had 2.5 times (95% confidence interval [CI], 1.4-4.2; P <.001), 2.9 times (95% CI, 1.7-4.9; P <.001), and 2.6 times (95% CI, 1.4-4.6; P =.002) greater odds of reporting 2 × MCIC in urinary QOL score compared with EBRT. There were no differences beyond 29 months. EBRT+BT led to a slower rate of urinary QOL symptom score resolution up to 17 months after radiation therapy compared with EBRT (P <.001) but not at later intervals. In contrast, at the end of the radiation therapy period and at 53 months after radiation therapy, the EBRT+BT group had 0.65 times (95% CI, 0.44-0.96; P =.03) and 0.51 times (95% CI, 0.32-0.79; P =.003) the odds of reporting 2 × MCIC in bowel QOL symptom scores compared with EBRT. There were no significant differences in the rate of bowel QOL score resolution. There were no significant differences in global health status or sexual activity scores between the 2 groups. There were no persistent differences in patient-reported QOL measures between EBRT alone and EBRT+BT. BT boost does not appear to negatively affect long-term, patient-reported QOL. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer.Methods and Materials: Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group.Results: A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P < .0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups.Conclusions: Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial. [ABSTRACT FROM AUTHOR]

We provide the strongest evidence to date that local failure is an independent prognosticator of outcomes in high- and intermediate-risk prostate cancer patients treated with definitive radiation therapy. Distant metastasis predominantly develops from a clinical relapse-free state; however, a second wave of distant metastasis occurs subsequent to local failure, albeit less commonly. The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06–1.30), PCSS (HR 2.02, 95% CI 1.75–2.33), and DMFS (HR 1.94, 95% CI 1.75–2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36–1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21–0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a "second wave" of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it. [ABSTRACT FROM AUTHOR]

Background: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups.Methods: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3-4 months to 6-9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4-6 months to 18-36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855.Findings: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0-15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77-0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78-0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83-1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group.Interpretation: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended.Funding: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology. [ABSTRACT FROM AUTHOR]

Purpose: Recent voxel-based studies have shown that the dose to specific rectal and urethro-vesical subregions is predictive of toxicities after prostate cancer intensity modulated radiation therapy. The objective of this study was to validate the discriminatory power of these subregions with respect to the whole organs in a large independent population.Methods and Materials: The validation cohort consisted of 450 patients from the TROG03.04-RADAR trial treated with 3-dimensional conformal radiation therapy at 66 to 74 Gy. Previous voxel-based analyses identified an inferoanterior rectal subregion as predictive of rectal bleeding and 5 subregions in the urethra and the posterior and superior part of the bladder as predictive of urinary incontinence, dysuria, retention, and hematuria. In the validation cohort, these subregions were segmented in each patient's anatomy. Dose-volume histograms (DVHs) of the whole organs and the 6 subregions were compared bin-wise between patients with and without toxicities. The discriminatory power of DVHs for grade ≥2 toxicity endpoints was assessed using the area under the receiver operating characteristic curve (AUC).Results: Subregion DVHs were significantly different between patients with and without toxicities for late rectal bleeding (V44-V74), acute urinary incontinence (V68-V72), late dysuria (V56-V68), and late retention (V14-V64). The dose to the rectal subregion and the whole rectum were equally predictive of rectal bleeding (V68; AUC = 0.61). The doses to 3 out of the 5 urethro-vesical subregions were found to be more predictive than the dose to the whole bladder: in the urethra for acute incontinence (V71 AUC = 0.69 vs V71 AUC = 0.66), in the posterior part of the bladder for late dysuria (V65 AUC = 0.66 vs V68 AUC = 0.59), and late retention (V39 AUC = 0.74 vs no significant AUC).Conclusions: Three subregions located in the urethra and the bladder were successfully validated as more predictive of urinary toxicity than the whole bladder for urinary incontinence, retention, and dysuria. Sparing the posterior part of the bladder in particular in treatment planning may reduce the risk of late urinary retention. [ABSTRACT FROM AUTHOR]

Background and purpose To evaluate the impact of treatment planning and delivery factors on treatment outcome as measured by post-treatment disease progression. Materials and methods Accruing 813 external beam radiotherapy participants during 2003–2007, the RADAR trial collected a comprehensive range of clinical treatment factor data for each participant. Both the Fine and Gray competing risks modelling and the Kaplan–Meier (KM) analysis were undertaken to determine the impact of these factors on local-composite progression (LCP), with 709 participants available for analysis. Results Participants with treatments involving 7 or more beams experienced significantly higher incidence of LCP, with a sub-hazard ratio (relative to 3-beam participants) of 3.056 (CI: 1.446–6.458, p  < 0.0034). Participants treated with a more rigorous dose calculation algorithm also displayed significantly higher incidence of LCP, with a sub-hazard ratio of 1.686 (CI: 1.334–2.132, p  < 0.0001). The KM analysis resulted in the same groups showing a higher incidence of LCP, with log-rank test results of p  = 0.0005 and p  = 0.0008 respectively. Conclusions The RADAR dataset has enabled a successful secondary analysis in which the impact of technical modifications has been assessed, challenging several established hypotheses. Increasingly precise treatments should be complemented with increasing accuracy to avoid potential geometric miss. [ABSTRACT FROM AUTHOR]