Prostate Radiotherapy Research Articles

A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life.

The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT). Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms. A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5-69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11-11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16-9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel. In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function.

COmparing Urolift and Standard Transurethral resection of prostate Ahead of Radiotherapy in men with urinary symptoms secondary to prostate enlargement in Southwest London and North Cumbria (CO-STAR): a study protocol for a randomised feasibility study

IntroductionPatients undergoing prostate radiotherapy with an enlarged prostate can have short-term and long-term urinary complications. Currently, transurethral resection of the prostate (TURP) is the mainstay surgical intervention for men with...

Long-Term Quality-of-Life Outcomes After Prostate Radiation Therapy With or Without High-Dose-Rate Brachytherapy Boost: Post Hoc Analysis of TROG 03.04 RADAR

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.

Health-related quality of life of metastatic prostate cancer patients treated with prostate Radiotherapy

BackgroundThe impact of prostate radiotherapy on patient-reported health-related quality of life (HRQoL) significantly influences the outcomes of metastatic prostate cancer. We measured and compared HRQoL of metastatic prostate cancer patients who received cytoreductive prostate radiotherapy.MethodsBetween November 23, 2020, and November 21, 2022, we recruited 70 metastatic prostate cancer patients at the Department of Clinical Oncology at Suez Canal University Hospital. Patients were eligible if they had synchronous and metachronous histopathological confirmed metastatic adenocarcinoma and an Eastern Cooperative Oncology Group performance status ≤ 2. Random allocation was performed for either definitive local radiotherapy concurrent with the standard androgen deprivation therapy (ADT) or to the standard ADT alone. Definitive radiotherapy was delivered conventionally (70 Gy/35 fractions) or through the hypofractionated regimen (55 Gy/20 fractions). Patients completed the comprehensive European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PR25) at baseline, then at three-month intervals for one year. The primary endpoint was patient-reported HRQoL, with secondary endpoints including toxicity and radiographic progression-free survival (rPFS). Mean HRQoL scores between groups were compared using the independent samples t-test.ResultsWe observed clinically significant improvements in urinary and bowel functions between baseline, 3-month, 6-month, and 12-month intervals after receiving definitive prostate radiotherapy. Patients in the radiotherapy group had significantly lower urinary symptoms scores than the control group. However, sexual activity and functioning showed significant deterioration.ConclusionCytoreductive prostate radiotherapy in metastatic prostate cancer patients significantly improved urinary functioning, preserved bowel functioning but was associated with worsening of sexual functioning.Trial RegistrationThis trial was registered on (27/04/2023) with pactr.samrc.ac.za, PACTR202305854600529, URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25510.

Clinical Evaluation of Deep Learning-Based Auto-Segmentation toward MRI-Only Prostate Radiotherapy.

Due to its superior soft-tissue contrast, MRI is the imaging modality of choice for target and organs-at-risk delineation in prostate radiotherapy. A recent advanced MR scanner allows for an MRI-only workflow owing to its ability to generate synthetic CT (MRCAT) that enables accurate dose calculation and treatment planning. While auto-segmentation algorithms for CT images are increasingly being adopted in clinical practice, there are fewer such algorithms for MRI images. The purpose of this study was to evaluate a deep learning-based auto-segmentation tool (from MVision AI) for both MRI and MRCAT images. We hypothesize that such algorithms could produce accurate contours that require little manual editing, resulting in significant time saving and workflow efficiency in MRI-only treatment planning. T2 MRI and MRCAT image pairs (acquired on a Philips Ingenia 1.5T MRI Scanner) for 10 prostate patients treated in an MRI-only workflow at our institution were retrospectively collected with IRB approval. These image volumes were then segmented using deep learning-based auto-segmentation models trained for MRI and CT images, respectively. The structures were manually edited by an experienced physician in a commercial imaging informatics system (Velocity). Finally, the auto-segmented and the post-edit structures were compared using Dice Similarity Coefficient (DSC) and 95% Hausdorff Distance (HD95). Excellent agreement was found between the auto-segmented and post-edit structures. For MRCAT, the average DSC was 0.92±0.03, 0.99±0.00, 0.90±0.06, 0.89±0.07, 0.89±0.06, 0.95±0.04, and 0.96±0.03 for prostate, bladder, rectum, penile bulb, seminal vesicles, left femur, and right femur, respectively. The average HD95 for these structures were 0.65±0.51mm, 0.01±0.01mm, 2.07±1.68mm, 1.10±0.91mm, 1.67±1.81mm, 0.86±1.24mm, and 0.67±1.49mm, respectively. For MRI, the average DSC was 0.96±0.02, 0.99 ±0.00, 0.96±0.03, 0.87±0.03, 0.94±0.06, and 0.89±0.11 for prostate, bladder, rectum, penile bulb, seminal vesicles, and Barrigel spacer, respectively. The average HD95 was 0.25±0.21mm, 0.00±0.00mm, 1.60±1.87mm, 1.43±0.98mm, 0.50±0.86mm, and 1.56±2.26mm, respectively. We evaluated the clinical acceptability of deep learning-based auto-segmentation models for prostate radiotherapy, one for MRI and one for MRCAT delineation. Both models demonstrated superior accuracy, and a high degree of consistency, offering the potential for significant time saving in treatment planning and improved workflow efficiency.

Association of Prostate Specific Antigen Kinetics after Testosterone Recovery with Subsequent Recurrence: Secondary Analysis of a Phase III Randomized Controlled Trial.

The combination of short-term androgen deprivation therapy (ST-ADT) with prostate radiotherapy (RT) is a standard of care for patients with localized prostate cancer (LPCa). After cessation of ST-ADT, it takes about 8 to 10 months for the testosterone (T) to recover to supracastrate levels, which could drive changes in PSA kinetics. It largely remains unknown whether early changes in PSA kinetics after T recovery could predict for subsequent biochemical relapse. We performed a secondary analysis of a phase III randomized controlled trial in which patients with newly diagnosed LPCa with Gleason score £7, clinical stage T1b to T3a, and PSA <30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate RT (76 Gy in 38 fractions over 7.5 weeks) or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate RT. Clinical assessment and laboratory investigations were repeated 1 month after completion of ADT, every 4 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after recovery of T to a supracastrate level (>50 ng/dL). Patients with ³3 PSA measurements after T recovery to supracastrate level were included in this analysis. Fine and Gray cumulative incidence of biochemical recurrence (BCR) was calculated in patients with PSADT at or above median versus below median. Deaths were considered as competing events. All endpoints were calculated from the time of T recovery to supracastrate level. Subdistribution hazard ratios (sHR) with 95% confidence intervals (CI) were estimated for association of PSADT with relative incidence of recurrence using competing risk regression after adjusting for tumor stage, pre-treatment PSA, Gleason score, treatment regimen, and age at randomization. Overall, 311 patients were eligible for this analysis. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years was 31.0% and 20.7% in patients with PSADT <8 months and ³8 months, respectively. Longer PSADT was associated with a significantly lower risk of cumulative incidence of BCR (sHR for PSADT as a continuous variable 0.43, 95% CI: 0.28-0.66; sHR for PSADT ³8 months 0.54, 95% CI: 0.30-0.99). After adjustment for time to recovery of T to supracastrate level in addition to the aforementioned variables, longer PSADT (³8 months) was associated with lower risk of cumulative incidence of BCR (sHR: 0.53, 95% CI: 0.27-1.01). These findings suggest that early PSA kinetics within 18 months of recovery of T to a supracastrate level predict for subsequent biochemical failure. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit greater personalization of management decisions.

CT vs. MRI: Which is More Accurate in Grading Rectal Wall Infiltration after Hydrogel Spacer Placement for Prostate Cancer Patients?

The purpose of this study was to evaluate the incidence and severity of rectal wall infiltration (RWI) in prostate cancer patients after rectal hydrogel spacer implantation, a commonly used procedure to minimize rectal radiation exposure during prostate radiotherapy. The study aimed to determine correlation of RWI using computed tomography (CT) scans and magnetic resonance imaging (MRI) scans in order to determine the optimal post-placement imaging modality. This retrospective study was conducted on 370 patients diagnosed with localized prostate cancer who underwent rectal hydrogel spacer placement from 2020 to 2022. CT scans were performed on all patients, with a smaller subset also undergoing MRI scans. The images were independently evaluated by three radiation oncologists to grade RWI levels using a standardized scoring system based on CT and MRI images after hydrogel placement. The levels were categorized as 0 (no RWI), 1 (focal RWI), 2 (moderate RWI), and 3 (significant RWI). Any grade of RWI was identified in 79.8% of men with the majority (41%) being RWI grade 1. The median time for CT scans was 9 days after hydrogel spacer placement and 14.5 days for MRI scans. For the subset of patients with both CT and MRI scans after spacer (mostly SpaceOAR Vue), RWI was detected in 58.33% of patients based on CT and 61.11% of patients based on MRI. Table 1 shows the mean percentage of patients with each score of RWI for each imaging modality. MRI was more likely to lead to a designation of RWI of any grade compared to CT and more often led to detection of RWI grades 2-3. Our findings demonstrate that the incidence and severity of RWI may be higher than previously reported in clinical trials and that MRI may be a more sensitive imaging modality. Caution is needed in the utilization of rectal spacer gels given the potential for complications with misplacement prior to radiation therapy. Further study is warranted to determine the potential impact of low-grade RWI on the safety of subsequent treatment.

One Year Radiographic Response Following Prostrate SBRT: An Exploratory Analysis of a Phase III Randomized Trial.

Radiographic MRI response following prostate radiotherapy, particularly stereotactic body radiotherapy (SBRT), remains poorly understood. Our objective was to describe radiographic changes to the prostate gland and prostate tumor following SBRT of men treated on a prospective, randomized trial. MIRAGE (NCT04384770) is a single center, randomized phase III trial of patients receiving either CT or MRI guided SBRT for localized prostate cancer. Patients underwent pre-treatment and annual post-treatment MRIs, in addition to routine PSA surveillance. Outcomes reported include percent gland shrinkage, percent PSA response at one year, and presence of residual tumor based on radiographic interpretation. Patient characteristics were compared via two-sample t-test or Fischer's exact test. Both univariate and multivariable logistical analysis were employed to identify potential clinical predictors of residual tumor on 1-year follow up MRI. This study cohort included 94 eligible patients with baseline characteristics in Table 1. Residual lesions were seen in 13 patients (14%), 5/27 (18.5%) treated without ADT and 8/67 (12%) with ADT. PSA ablation was deep, with a 79% median decrease without ADT and 98% median decrease with ADT. Patients receiving ADT showed more gland shrinkage (17% vs. 34% shrinkage, p = 0.0001), while radiographic non-responders and responders experienced similar gland shrinkage (median 21% vs 29% shrinkage, p > 0.05). No significant clinical predictors of residual tumor were identified on univariate and multivariate analysis. No patient had any clinical or biochemical evidence of failure. A total of 14% of patients were found to have residual tumor detected on MRI one year after SBRT. These data highlight the protracted nature of radiographic tumor response to radiation therapy, even with ablative radiation techniques. The analysis is limited by the lack of biopsy data to quantify whether visualized residual tumor harbor active cancer.

Optimal Planning Target Margin for Prostate Radiotherapy Based on Interfractional and Intrafractional Variability Assessment during 1.5T MR-Guided Radiotherapy.

MR-guided radiotherapy (MRgRT) provides superior soft-tissue contrast over CT-based image guidance. We collected and analyzed daily pre-treatment (PRE) and real-time motion-monitoring (MM) MR images of patients receiving prostate radiotherapy to assess interfractional and intrafractional variability of prostate using two localization methods: pelvic bony anatomy (bone) and prostate during online adaptive radiotherapy (ART). PRE and MM MRIs for the first five fractions of twenty prostate cancer patients who received definitive MRgRT with 1.5T MRI were collected. Using MIM software, rigid registration between PRE MRI and planning CT images based on pelvic bony anatomy and prostate reproduced bone localization and online ART, respectively. To determine interfractional setup margin (SM), prostate was delineated on all PRE MRIs registered after bone and prostate localizations by a radiation oncologist, and centroid values of prostate contours between planning CT and PRE MRIs were compared. To determine interobserver variability, another radiation oncologist, a medical physicist, and a radiotherapist contoured prostate for both localization methods. For internal margin (IM) assessment, we used MM MRIs of the five patients who had all three sets of coronal, sagittal, and axial cine images and determined the maximum contour displacement using in-house MATLAB-based software converting binary image files to 2D cine images with a superimposed grid of 1 mm spacing. A total of 100 PRE and 25 MM MRIs were analyzed. Four hundred prostate contours were delineated on MR images registered with planning CT based on both bony anatomy and prostate. After bone localization, SM was 0.57±0.42 mm in left-right (LR), 2.45±1.98 mm in anterior-posterior (AP), and 2.28±2.08 mm in superior-inferior (SI) directions, and IO was 1.06±0.58 mm in LR, 2.32±1.08 mm in AP, and 3.30±1.85 mm in SI directions. After prostate localization, SM was 0.76±0.57 mm in LR, 1.89±1.60 mm in AP, and 2.2±1.79 mm in SI directions, and IO was 1.11±0.55 mm in LR, 2.13±1.07 mm in AP, and 3.53±1.65 mm in SI directions. Average IM was 2.12±0.86 mm, 2.24±1.07 mm, and 2.84±0.88 mm in LR, AP, and SI directions, respectively. Using daily MRIs from MRgRT, we showed that movements in the SI direction were the largest source of variability in prostate definitive RT. In addition, interobserver variability was a non-negligible source of margin. Optimal PTV margin should also consider internal margin, especially in the SI direction.

Prospective Validation of Single Nucleotide Polymorphisms as Predictors of Gastrointestinal, Genitourinary, and Sexual Patient-Reported Outcomes Following Radiotherapy for Prostate Cancer.

Radiotherapy (RT) for localized prostate cancer (PC) can adversely impact gastrointestinal (GI), genitourinary (GU), and sexual quality of life (QoL). Biomarkers are needed to accurately predict individualized risk of toxicity and enable tailoring of therapy. Single nucleotide polymorphisms (SNPs) have been reported as potential predictors of RT-related toxicities, but have not been associated with patient-report outcomes (PRO) in prospective cohorts. In this study, we sought to validate these SNPs in a prospective registry study of RT for PC, with high-quality prospectively collected PRO data. Men with low/intermediate risk PC were consented to a multicenter companion registry study associated with the PARTIQoL Phase III Randomized Trial of proton vs. photon RT. Patients received RT to prostate/seminal vesicles per protocol. Androgen deprivation therapy and pelvic lymph node RT were not allowed. 95 patients enrolled between 2014-2020 at a single institution had blood specimens available for germline DNA analysis. 172 SNPs previously reported to correlate with GI, GU, and/or sexual RT toxicities were genotyped. PRO data through the Expanded Prostate Cancer Index Composite (EPIC) were collected prior to RT and at prespecified follow-up (FU) time points. Change of the EPIC score from baseline was compared between genotypes of previously identified SNPs using a two-sample t-test. Significant clinically meaningful QoL differences were identified by an effect size of at least 0.4σ with two-sided p<0.05, where σ represents the standard deviation of the score change. Median FU was 39 months (r, 6-89). Median age was 68 years (r, 52-83). Features at diagnosis include: 77% T1c, median PSA 5.8 (r, 1.43-15.1), 53% Gleason 7, median prostate volume 45.5cc (r, 16-142). 43% received proton RT; 53% had a rectal spacer. 40% received 79.2 Gy/44 fractions; 60% received 70 Gy/28 fractions. Between 6 to 24 months post-RT, there were 19 SNPs that were significantly associated with clinically meaningful decreases in GI QoL scores, 19 that were significantly associated with clinically meaningful decreases in GU QoL scores, and 10 SNPs that were significantly associated with clinically meaningful decreases in sexual QoL scores. Three BRCA2 SNPs (rs1801439, rs1801499, rs1799944) were significantly associated with clinically meaningful decreases in both GI and GU QoL scores. Of the 172 SNPs previously reported to be associated with GI, GU, and/or sexual toxicity after prostate RT, 23% were validated for domain-specific QoL detriment. Ongoing analyses include integrated modeling of dosimetry and SNP data for prediction of toxicities and PRO, and evaluation of potential interactions between RT modality (proton/photon) and QoL-associated SNPs.

A Systematic Review and Network Meta-Analysis Assessing the Impact of Adding First Generation Non-Steroidal Anti-Androgens (NSAA) to LHRH Agonists (LHRHa) in Men Receiving Radiotherapy for Localized Prostate Cancer.

Randomized clinical trials consistently demonstrate that the addition of androgen deprivation therapy (ADT) to prostate radiation therapy improves overall survival (OS). However, there is substantial heterogeneity regarding the type of ADT: LHRHa alone, first generation NSAA alone (e.g., bicalutamide) or combination androgen blockade (CAB) with NSAA and LHRHa. There are no published randomized trials in localized disease that specifically compare the efficacy of NSAA to LHRHa, nor the utility of CAB over monotherapy ADT. We herein performed a systematic review and network meta-analysis to assess the impact of NSAA in relation to LHRHa in men receiving radiotherapy for localized prostate cancer. We performed a systematic literature search in PubMed to identify clinical trials of patients with localized prostate cancer for which ADT duration was the primary randomization variable. Both definitive and salvage radiation trials were included. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from data extracted from published survival curves. A network meta-analysis was performed to compare OS by ADT regimens. We defined NSAA toxicity as early discontinuation of any ADT agent due to side effects given the inconsistent reporting of specific related toxicity. A meta-regression was performed to assess association with NSAA toxicity, adjusted for study year, patient age, T stage, Gleason score and total ADT duration. NSAA duration was assessed as a continuous variable. Of the 11 trials (8,169 patients) with OS data, the median duration of any ADT was 3 months (range 0-36 months) and the median duration of NSAA specifically was 3.5 months (range 0-24 months). There was no significant difference in OS between those treated with LHRHa (n = 369) vs. CAB (n = 4,792; HR 1.10, 95% CI 0.78-1.55). Among those receiving CAB, increased NSAA duration did not improve OS (versus 0 months; 1-6 months HR 1.41, 95% CI 0.94-2.13; 7-12 months HR 1.43, 95% CI 0.87-2.34) when controlling for total ADT duration. Of the 19 trials (15,067 patients) with toxicity data, patients on NSAA (n = 503) appeared more likely to discontinue treatment early compared to those receiving LHRHa (n = 902), though this was not statistically significant (odds ratio [OR] 4.20, 95% CI 0.16-109.19). A longer duration of NSAA did not adversely affect ADT compliance. Patients were more likely to discontinue ADT prematurely, regardless of type, if the planned duration was longer (OR 1.08, 95% CI 1.07-1.09). We did not detect an overall survival benefit to adding NSAA to LHRHa, and NSAA appeared less well tolerated than LHRHa in men receiving radiation therapy for localized prostate cancer. These data suggest that providers should consider LHRHa without the addition of a NSAA as optimal when clinically appropriate.

Prophylactic Α-Blockers for Radiotherapy-Induced LUTS in Men with Prostate Cancer: A Phase III Randomized Trial Analysis.

Radiation therapy (RT) to the pelvis is one of the curative approaches for patients with localized prostate cancer. Most patients treated with prostate RT experience some degree of radiation-induced lower urinary tract symptoms (RI-LUTS). The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTS in prostate cancer patients receiving external beam radiotherapy (EBRT). A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic Silodosin at day one of EBRT or at the time of RI-LUTS. LUTS 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. 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 (95% CI -4.5 to 1.8, p = .40). There were no significant differences in IPSS between the study arms in the intention-to-treat (ITT) analysis at baseline, last day of RT, 4 weeks and 12 weeks post-RT. The as-treated analysis however, identified statistically significant difference at 4 weeks post-RT (95% CI -6.4 to -0.4, p = .03) in favor of prophylactic α-blockers. In an exploratory analysis, patients with prostate volumes less than or equal to 50 cc benefited at 4 weeks post-RT from prophylactic α-blocker (95% CI -8.4 to -0.3, p = .04). Prophylactic α-blocker was not effective at significantly reducing RI-LUTS in prostate cancer patients treated with EBRT. Treating patients with α-blocker at the onset of RI-LUTS will avoid unnecessary drug exposure and toxicity. There may be a benefit for prophylactic α-blocker in patients with smaller prostate. This however, needs to be further studied in a larger study.

Long-Term Effectiveness of a Nonsurgical BPH Treatment System in Prostate Radiation Patients with Medication-Refractory Lower Urinary Tract Symptoms.

To evaluate the long-term outcomes and toxicity of a nonsurgical prostatic urethral lift system in patients with prior prostate cancer radiation therapy (RT). From 2018 to 2020, nineteen patients with a history of prior prostate RT underwent a nonsurgical prostatic urethral lift (PUL) procedure for lower urinary track symptoms (LUTS) refractory to alpha blocker medications. Prostate cancer RT was completed a median of 17.8 months (IQR 13.4-27.4) prior to PUL procedure. All patients were assessed with IPSS/quality of life (QOL) scores and urinary post void residual (PVR) ultrasound before and after PUL. Patients were also assessed for ability to discontinue alpha blockade medications for their LUTS and any post PUL toxicity based on CTCAE v5.0 criteria. All patients underwent successful placement of the PUL implants. Median pre-PUL IPSS score was 20 (IOR 17.5-22.5) and the median prostate volume was 41cc (IQR 33-49). Median follow up was 22 months (IQR 5-30). The average improvement in IPSS score was 8.5 points (IRQ 5.5-11) at 3 months and 7.5 points (IQR 6-10) at last follow-up. Two patients (10%) initially had improvement in IPSS score at 3 months with subsequent significant increase in IPSS (>5 points) at last follow-up. Overall, there was minimal change in reported QOL scores (median 0, IQR 0-1.75). The average reduction in PVR was 90cc. The percentage of patients able to discontinue alpha blockade at last follow-up was 68%. There was no grade 3 or higher GU toxicity in either group. Use of a nonsurgical prostatic urethral lift system in patients with prior prostate RT refractory to alpha blocker medications results in significant long-term improvement of LUTS after radiation therapy for the majority of patients with minimal toxicity.

Online Correction of Intrafraction Motion during Volumetric Modulated Arc Therapy for Prostate Radiotherapy: A Cohort Study Quantifying the Frequency of Shifts and Analysis of Men at Highest Risk.

We have previously described our early experience using fiducial markers to correct for intrafraction motion during radiation therapy (RT) to the prostate using the TrueBeam Advanced imaging package. We sought to further characterize the utility of this approach in a larger cohort, and analyze factors associated with intrafraction motion. A total of 132 men with fiducial markers treated with RT for intact prostate cancer at a single center were treated with a VMAT technique using 2-3 arcs. All patients underwent planning CT after a rectal enema and same day placement of 3 fiducial markers (Gold Anchor). Triggered kV images were acquired every 10 seconds using an onboard imaging system. Intrafraction motion correction was considered if any two fiducial markers were observed beyond a 3 mm tolerance margin. A manual 2D-3D match was performed using the fiducial markers from the single triggered kV image to obtain a couch shift. Shift data were extracted from the record and verify system and expressed as a single 3-dimensional translation. Shift percent was defined as the number of instances of a >3 mm intrafraction correction divided by the total number of fractions for a given patient. Clinical variables were evaluated, including body mass index, hormone therapy (ADT), prostate, rectal bladder volumes, and rectal width (transverse dimension of rectum at the mid-gland of prostate on simulation CT). Across 2659 fractions, intrafraction motion correction was performed 582 times, in 463 fractions (17%). 101/132 patients (77%) had at least one shift during their treatment course, and 48/132 patients (36%) had shifts with an average magnitude of at least 5 mm. The median shift was 3.6 mm (range, 0-2.4 cm; IQR, 1.5-5.4 mm). 25% of men had a shift percent >20% (SP>20%). Univariate analysis revealed that only larger rectal volume or width, smaller prostate size, and use of ADT were associated with SP>20% (p<0.05). Men with rectal width in the top quartile (>3.6 cm) were more likely to have intrafraction motion corrected with SP>20% (47% vs 18%, p = 0.0016), and similarly men with rectal volume in the top quartile (>112 cc) were more likely to have SP>20% (44% vs 19%, p = 0.0067). On multivariate analysis, only rectal parameters (e.g., top quartile rectal width, HR 3.9, p = 0.0024) were correlated with a higher frequency of intrafraction motion. Intrafraction motion occurs in a significant percentage of men undergoing prostate RT with VMAT, and is correctable utilizing a common feature. On multivariate analysis, rectal volume and width were associated with larger shift percent. Treatment approaches which do not account for intrafraction motion should consider including methods of immobilization, or larger PTV margins in order to avoid marginal miss of the prostate.

Real-World Toxicity of Conventional Versus Hypofractionated Definitive Prostate Radiotherapy across a Large, Diverse, Academic and Community-Based Enterprise.

Over the past 10-15 years there has been increasing adoption of moderate hypofractionation (HF) for definitive prostate radiotherapy as compared to conventional fractionation (CF). Based on several randomized trials hypofractionation results in equivalent treatment efficacy with similar rates of long-term toxicity. However, some studies suggest higher acute GI toxicity with moderate hypofractionation. We sought to compare the rates of toxicity between these two groups across our enterprise including 16 community-based practices and one academic NCI-designated comprehensive cancer center. We retrospectively extracted radiation treatment intent from our network-wide clinical pathways for patients diagnosed with prostate cancer between 3/2019 and 10/2022. Patients treated after prostatectomy and those treated with brachytherapy or SBRT were excluded. For the remaining 1529 patients treated with either conventional fractionation or moderate hypofractionation, we identified and merged physician-graded toxicity data using CTCAE version 5.0 recorded in their electronic medical record at each weekly on-treatment visit and follow-up. A total of 1051 patients had toxicity data available. Rates of toxicities were then compared between the cohort of patients who received CF and those who HF using the Chi-square test. Of the 1051 patients, 450 (43%) received CF and 601 (57%) received HF. These patients were treated by 40 different radiation oncologists (median patients per physician = 18, interquartile range = 7-35). Median age in the CF and HF cohorts was 71 (IQR: 66-76) and 71 (IQR: 66-77; p = 0.51), respectively. The CF cohort had more patients with Gleason 8+ disease (39% vs 19%; p<0.01), PSA >20 (26% vs 11%; p<0.01), or T3a+ (18% vs 8%; p<0.01). Rates of any grade 2+ toxicity were significantly higher in patients who received HF at 45.8% vs 39.6% for those treated with CF (p = 0.04). However, the respective rates of any grade 3+ toxicity were no different at 2.0% vs. 1.8% (p = 0.80). The difference in grade 2 toxicities appeared to be primarily driven by the rates of urinary frequency at 27.1% vs. 17.8% (p<0.01) and prostatic obstruction 14.8% vs. 10.2%, p = 0.03). Rates of grade 2 diarrhea were worse with MF at 5.3% vs. 2.8% for CF (p = 0.04). There were no significant differences between HF and CF in the rates of grade 2 dysuria (6% vs 5.2%), urinary urgency (6.5% vs. 4.2%), proctitis (3.0% vs. 3.6%), urinary incontinence (0.5% vs. 1.3%), rectal bleeding (0.3% vs. 0%), hematuria (0% vs. 0.4%), and fatigue (14.1% vs. 15.1%). In this large network-wide analysis, toxicity was slightly increased among patients with prostate cancer treated with HF compared to CF, consistent with published randomized data. However, the increased toxicity appeared to be primarily GU rather than GI. This study demonstrates the feasibility of analyzing impacts of treatment decisions on a large scale using real-world data through an integrated network of practices.

1782P Prostate radiotherapy reduces long-term risk of obstructive uropathy in metastatic hormone sensitive prostate cancer (mHSPC): Results from the STAMPEDE M1|RT comparison

1782P Prostate radiotherapy reduces long-term risk of obstructive uropathy in metastatic hormone sensitive prostate cancer (mHSPC): Results from the STAMPEDE M1|RT comparison

Biochemical Failure in Intermediate Risk Prostate Cancer: Then What? Long-Term Data from a Phase III Trial.

Aiming to determine long-term outcomes post biochemical failure (BF) in patients (pts) treated for intermediate-risk prostate cancer, we analyzed data from our prospective randomized trial (PCS III). From December 2000 to September 2010, 600 pts with intermediate risk prostate cancer (IRPC) received prostate radiotherapy (RT) with or without short-term (6 months) androgen deprivation therapy (ADT) on a Phase III trial. We report death rate from prostate cancer, rate and timing of BF plus the final clinical outcome of patients, alive or dead, with BF. Chi-squared test was used to compare BF and prostate cancer progression (PCP) rates between patient with or without ADT. Median age at randomization was 71 years (IQR 66-74). With a median follow-up (FU) of 13.5 years (IQR 11.2-17.0), 74.5% (447/600) were free from BF at last FU. Of these, 211 died, 79 stopped FU after 10 years, 9 were lost to FU, 6 withdrew from the study and 142 are still on FU, at a median follow-up of 13.2 years (IQR = 10.9 - 16.2). A total of 153 pts (25.5%) developed BF at a median time of 6.5 years post-randomization. Among BF pts, 82/153 died: we documented 32 deaths from prostate cancer (DPC) at a median time of 6 years post-BF and 50/153 pts died from other causes at a median time of 4.7 years from BF. 48/153 BF pts continue on FU: 34 show no clinical evidence of cancer, 9 developed a second cancer and 5 show clinical evidence of PCP. 20/153 pts stopped FU after 10 years: 3 of them with PCP. 3/153 pts were lost to FU: 1 after 3 years with prostate bone metastasis and 2 after 13 years of FU. In the first 5 years post-randomization, 47 pts (7.8%) presented BF with 1 (0.2%) DPC; between 6 and 10 years, there were another 84 (14%) BFs and 11 (1.8%) DPC. Finally, after 10 years and beyond, we recorded an additional 22 (3.7%) BFs and 20 (3.3%) DPC. The rate of patients who received ADT was significantly lower in patients with BF (74/153 = 48.4%) compared to patients without BF (324/447 = 72.5%), p<0.001. The rate of patients who received ADT was also significantly lower in patients with PCP (19/48 = 39.6%) compared to patients without PCP (379/552 = 68.7%), p<0.001. In our trial for intermediate-risk prostate cancer, a quarter of the pts developed BF. Most of the BFs occurred between 5- and 10- year post-randomization. Deaths due to prostate cancer post-BF occurred at a median time of 6 years, justifying the need for long-term FU. BF and PCP were significantly higher in patients not receiving ADT.

Validating a Simple Urethra Surrogate Model to Facilitate Dosimetric Analysis to Predict Genitourinary Toxicity.

The urethra may be a critical structure in prostate radiotherapy planning as some studies have shown that higher urethral dose correlates with worse genitourinary (GU) toxicity. Identifying the urethra requires an MRI planning scan or foley catheter insertion at CT planning. Most surrogates have been developed and validated against the urethra identified by a foley catheter. However, the urethral position can shift with catheter placement. We, therefore, aim to validate a simple urethra surrogate model against MRI-defined urethra. The surrogate model can be used to correlate urethra dose-volume parameters (DVP) with late GU toxicity and to apply urethral constraints in those with a CT-only based workflow. Thirty-nine MRI-defined urethras from patients in the PACE-C trial were assessed to determine the average position of the urethra in the midline sagittal prostate plane along the ¼ gland, midgland, ¾ gland, apex and 3mm below apex. Using these average positions, a Python script was developed, which places a 10mm diameter circle in the 1/4 gland, midgland, ¾ gland, apex and 3mm below the apex. The observer manually contours a 10mm circle at the prostate base (prostate-bladder neck interface) to infer the urethra position and interpolates the contours. The urethra surrogate model was compared against 20 MRI-defined urethras (within the treatment PTV) in patients treated with 36.25Gy in 5 fractions as part of the PACE-B trial. To assess the surrogate's geometric performance, the Dice similarity coefficient (DSC), Hausdorff distance (HD), mean surface distance to agreement (MDTA) and the percentage of MRI-defined urethra outside the surrogate (UOS) were calculated. The surrogate model's dosimetric performance was assessed by comparing the mean D99, D98, average dose, D50, D2 and D1 using a paired t-test. The D(n) is the dose (Gy) to (n)% of the urethra. The median results were: DSC 0.36 (IQR 0.28-0.42), HD 0.88cm (IQR, 0.70-1.04), MDTA 0.24cm (IQR, 0.21-0.28), UOS 29% (IQR, 17-52%). When comparing DVP between the MRI-defined urethra and surrogate urethra, the mean D99, D98 and D95 as 38.8Gy vs 39.1Gy (p = 0.17), 39.3Gy vs 39.5Gy (p = 0.23), 40.1Gy vs 40.4Gy (p = 0.21), respectively. The mean D50, average dose, D2 and D1 was 41.8Gy vs 41.9Gy (p = 0.03), 41.7 vs 41.8Gy (p = 0.04), 42.9Gy vs 43.0Gy (p = 0.05) and 43.0Gy vs 43.1Gy (p = 0.03), respectively. While there were geometric differences between the surrogate urethra and MRI-defined urethra, there was no statistically significant difference between most urethral dose-volume parameters (D99, D98, D95, and D1). Similarly, the actual differences in urethra DVP were not clinically significant. This surrogate model could be validated in a larger cohort and then used to estimate the urethra position on CT planning scans for dosimetric analysis in those without an MRI planning scan or urinary catheter.

The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Acute gastrointestinal (GI) and genitourinary (GU) toxicity after prostate radiotherapy (RT) has been shown to be associated with late toxicity with 3D conformal RT. However, whether this association is present with modern approaches, such as stereotactic body radiotherapy (SBRT), remains unclear. We analyzed patients treated within the international phase III non-inferiority randomized control trial, PACE-B, to assess the association between acute and late toxicity following SBRT and conventional/moderately hypofractionated radiotherapy (CRT). We hypothesize that acute toxicity is significantly associated with equivalent late toxicity following prostate SBRT and CRT. We analyzed patients with GI and GU Common Terminology Criteria for Adverse Events (CTCAE) measurements in the acute (≤12 weeks post-RT) and late period (6-24 months post-RT). Using logistic regression, we analyze the association between G2+ acute GI and GU toxicities with equivalent late toxicities. Lasso variable selection was used to determine patient, tumor and treatment variables to include in the multivariable model. The area under the receiver operator characteristics curve (AUC) was used to evaluate the model's predictive performance. Of patients included in this analysis (n = 842), 414 were treated with SBRT and 428 with CRT. In univariable analysis (UVA), G2+ acute GU toxicity was significantly associated with developing G2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96-7.25), p<0.0001) and CRT (OR 2.83, 95% CI (1.69-4.71), p<0.0001). This association remained significant in multivariable analysis (MVA). The models AUC for predicting G2+ late GU toxicity after SBRT was 0.73 (95% CI, 0.67-0.78) and 0.66 (95% CI, 0.59-0.73) following CRT. In UVA, G2+ acute GI toxicity was associated with developing G2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91-7.03), p <0.0001) and CRT (OR 4.4, 95% CI (2.04-9.47), p<0.0001). This association also remained significant in MVA. The models AUC for predicting G2+ late GI toxicity after SBRT was 0.66 (0.95% CI, 0.57-0.75) and 0.64 (95% CI, 0.57-0.72) following CRT. In UVA analysis, G2+ baseline GU symptoms were also associated with developing G2+ late GU toxicity after SBRT (OR 7.59, 95% CI (2.72-21.19, p<0.0001) and CRT (OR 7.98, 95% CI (3.03-20.96), p<0.0001), and this continued to be significant in MVA. Acute toxicity remained associated with persistent late toxicity (≥2 G2+ late events) and late toxicity 12-24 months. Our study demonstrates an independent association between acute and late GU/GI toxicity in patients treated with SBRT and CRT for localized prostate cancer. Recognizing those at risk of late toxicity can provide an opportunity for early intervention to improve outcomes. G2+ acute toxicity should be considered an essential variable for predicting late GI/GU toxicity after prostate RT.

Dosimetry Validation of MR-Only Treatment Planning Based upon the Synthetic MRCAT Pelvis with Continuous Hounsfield Units in Prostate Cancer

MR-based radiotherapy delivery systems are increasingly encouraging treatment planning based upon an AI generated synthetic CT created from an MR image. Concerns remain concerning the dosimetric accuracy of this approach. to evaluate and compare the feasibilities and dosimetry of magnetic resonance (MR) image-based planning using pelvic synthetic computed tomography (sCT) versus conventional computed tomography (cCT) based planning. We used the new MRCAT pelvis MRI-SIM (1.5T) with continuous Hounsfield units for dose calculation. The hypothesis was that planning based upon sCT vs cCT would not lead to a difference in dose delivery. A total of 10 consecutive patients with prostate cancer representing a range of treatment regimens underwent both a conventional CT based 3d simulation and also an MR simulation from which an MRI-simulation procedure for calculating attenuation (MRCAT) image was generated. A VMAT plan was generated based upon the cCT, and then applied to the sCT without re-optimization. Delivered dose was recalculated on the sCT plan using the fixed monitor units previously optimized for the cCT. Dose volume histograms (DVHs) were calculated for targets and organs at risk (OAR) and compared with those achieved with the cCT. In addition, dose values from 10 different point-coordinates and dose distributions volumes (i.e., volume receiving 80%, 50%, 30% prescribe dose etc.) were compared. All patients were receiving definitive RT to prostate: 2 prostate and seminal vesicles and 8 prostate with lymph nodes were treated. Median prostate volume was 34.3 cc (range 29 cc-84 cc), median number of fractions was 12 (range 5 fr-26 fr), median prescription dose was 51.6 Gy (range 40 Gy-70.2 Gy). The mean dose to the prostate planning target volume and six different OAR were calculated on sCT and cCT, differed by 0.7% ± 1.3% (p = 0.02). Three dose distribution line volume between 30%-80% of prescribed dose, differed by 1.8%±3% (p = 0.02). Ten point-coordinate dose values from different tissues including bone, fat, air and muscle around the planning treatment volume differed by 0.4% ±0.7% (p = 0.03). There was a very small (∼ 1%), but clinically insignificant, difference in the dose distribution results obtained using sCT from MRCAT compared with those obtained with cCT. The Philips pelvic MRCAT, even in the absence of a cCT, is suitable for clinical treatment planning in prostate radiotherapy.