Expanded Prostate Cancer Index Composite Bowel Research Articles

Randomized Trial of Five or Two MRI-guided Adaptive Radiotherapy Treatments for Prostate Cancer (FORT)

The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 - 1 3. IPSS < 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP < 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from "no problem" to "very small problem") or one of the symptoms worsening by 2 levels (i.e., loose stool change from "no problem" to "small problem"). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Twenty patients. To be determined. To be determined.

Quality of life in patients who underwent robot‐assisted radical prostatectomy compared with those who underwent low‐dose‐rate brachytherapy

To compare the quality of life (QOL) in patients who underwent robot-assisted radical prostatectomy (RARP) or low-dose-rate brachytherapy (LDR-BT) for prostate cancer. We enrolled patients who underwent LDR-BT (LDR-BT alone [n = 540] or LDR-BT plus external beam radiation therapy [n = 428]) and RARP (n = 142). QOL was evaluated using the International Prostate Symptom Score, Expanded Prostate Cancer Index Composite (EPIC), Sexual Health Inventory for Men (SHIM), and 8-item Short Form (SF-8) health survey. The two groups were compared using propensity score matching analysis. At 24 months after treatment, the number of patients with worsened urinary QOL in the urinary domain of EPIC compared with baseline was 78/111 (70%) and 63/137 (46%) in the RARP and LDR-BT groups, respectively (p < 0.001). In the urinary incontinence and function domain, this number was higher in the RARP group versus the LDR-BT group. However, in the urinary irritative/obstructive domain, the number of patients with improved urinary QOL at 24 months compared with baseline was 18/111 (16%) and 9/137 (7%), respectively (p = 0.01). Regarding the SHIM score, sexual domain of EPIC, and mental component summary of SF-8, there were more number of patients with worsened QOL in the RARP group than in the LDR-BT group. In the EPIC bowel domain, the number of patients with worsened QOL was lower in the RARP group versus the LDR-BT group. The differences in QOL observed between patients treated with RARP and LDR-BT could assist in treatment selection for prostate cancer.

Randomized trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks vs. 2 weeks (SHORTER).

TPS400 Background: The objective of this randomized clinical trial is to demonstrate that 2 weeks (5 fractions) of real-time MRI-guided radiotherapy (RT) with an MR Linac does not significantly increase patient-reported GI and GU symptoms compared to 4 weeks (20 fractions) of RT 2 years after treatment completion. Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged &gt; 18 with histologically confirmed prostate cancer after prostatectomy with detectable PSA. 2. KPS &gt; 70. 3. Patients with no evidence of distant metastatic disease on PET/CT/MRI/bone scan&lt; 180 days prior to enrollment. 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. History of bladder neck or urethral stricture. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 5 fractions of ultrahypofractionated RT (32.5 Gy total with optional PSMA/MRI boost to 40 Gy) versus 20 fractions of hypofractionated RT (55 Gy total with optional PSMA/MRI boost to 60 Gy) in the post-operative setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 5 or 20 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and use of nodal treatment and ADT. Enrollment: 91 patients. Clinical trial information: NCT04422132 .

Randomized trial of five or two MRI-guided adaptive radiotherapy treatments for prostate cancer (FORT).

TPS399 Background: The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged &gt; 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 – 1 3. IPSS &lt; 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP &lt; 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Eleven patients. Clinical trial information: NCT04984343 .

An observational study evaluating the impact on prostate patient outcomes and experiences when radiation therapists use a standard grading system tool to assess and document treatment-related toxicities and interventions

Background/PurposeMen undergoing radiation therapy (RT) treatment for prostate cancer (PC) often experience acute urinary, bowel, sexual, and hormonal toxicities. Timely screening, management, and documentation of these toxicities is an integral part of clinician practice, ensuring patients receive the care they require. Various screening tools, completed by either the patient or the clinician, are available, which allow clinicians to collect and respond to these toxicity outcomes; however there is a paucity of literature regarding the effective use and timing of these tools during RT treatment. This study aims to evaluate the feasibility of conducting comprehensive toxicity screening and symptom management using a toxicity screening tool in one of the busiest RT departments in Canada. Specifically, the use of a toxicity screening tool and its effect on the quality of toxicity documentation, operational impact, and patient reported outcomes (PRO). Methods90 consented patients were allocated to either the structured or non-structured arm. Patients in the structured arm were assessed weekly by radiation therapists for 13 toxicities across four domains (bladder, bowel, hormonal, and sexual), using an in-house developed structured questionnaire, known as the Grid, to complete the National Cancer Institute's Common Toxicity Criteria for Adverse Events v3 (CTCAEv3). Patients in the non-structured arm were assessed and had free text clinical documentation charted according to current department policy. The Expanded Prostate Cancer Index Composite (EPIC), a PRO tool to evaluate patient function and bother after prostate cancer treatment, was completed by all study patients on a weekly basis. Statistical analysis compared documentation completeness, EPIC scores, patient satisfaction, and operational impact between study arms, as well as evaluated optimal timing of toxicity assessments. ResultsAssessment of the non-structured arm for completeness revealed an inconsistent and insufficient amount of documentation for the bladder and bowel domains. As for both the sexual and hormonal domains, documentation was largely absent. There was no difference in EPIC scores and patient satisfaction scores between the structured arm and the non-structured arm. Evaluation of the timing of PROs showed significant week to week change for the bladder and bowel toxicities, but not the sexual and hormonal toxicities. Finally, the use of the Grid revealed no significant impact on daily operations, only increasing average treatment times by seven seconds, and did not create any additional workload for the oncologists. ConclusionsUse of the Grid increased documentation completeness without negatively impacting clinical flow or operations, despite the fact that PROs were not improved. Based on EPIC PRO scores, bladder and bowel toxicities should be evaluated on a weekly basis during RT treatment, while sexual and hormonal toxicities need only be evaluated monthly.

Visceral Adipose Volume as a Predictor for Acute Bowel Toxicity in Patients Receiving Adjuvant Intensity-Modulated Radiation Therapy for Cervical or Endometrial Cancer

Relative to 3D conformal radiation therapy (RT), intensity modulated radiation therapy (IMRT) is associated with decreased acute bowel toxicity during adjuvant RT for gynecologic cancers. Delineating the peritoneal space as a 'bowel bag' is a common method to assess RT dose and volume parameters during treatment planning. However, there is a relative lack of evidence-based bowel bag dose/volume constraints that can be used to guide clinicians. Previously, we described a method to normalize dose/volume measures based on the proportion of adipose tissue within the bowel bag contour and demonstrated this technique more closely correlates with acute toxicity than standard measures. This work was criticized for including a heterogenous patient population of gastrointestinal and gynecologic cancer patients treated with definitive and adjuvant RT. Here, we report an updated analysis, limiting our patient population to those receiving adjuvant IMRT for gynecologic cancers.Eighteen consecutive patients treated with adjuvant pelvic +/- para-aortic IMRT following hysterectomy for a diagnosis of endometrial or cervical cancer at a single academic medical center were included. As previously described by Ganju et al, simulation CT scans were retrieved and the bowel bag was contoured per RTOG guidelines. Dosimetric data for V45 Gy (cc) and V40 Gy (%) was collected. Adipose tissue was auto-contoured using Hounsfield Unit thresholds. Visceral adipose ratio was defined as the volume of non-adipose tissue within the bowel bag divided by the total volume. This was multiplied by the above dosimetric variables to correct for uninvolved adipose tissue. Bowel function was assessed weekly during therapy using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Baseline bowel scores were defined as those obtained at CT simulation or week 1 of therapy, and final scores were those occurring during week 4 of 5 of treatment. One-tailed spearman correlation coefficients were used to identify significant associations between acute bowel toxicity and bowel bag dose/volume measures.Eighteen patients met criteria for inclusion. Fifteen patients were treated for endometrial and three for cervical cancer. The median dose of radiation was 45 Gy. V40 Gy (%) and V45 Gy (cc) measures were not correlated with decline in EPIC bowel function, bother, or composite measures. However, adipose corrected V45 Gy(cc) showed significant correlation with bowel function decline (P = 0.04) and overall decline in bowel composite measure (P = 0.03).Adipose corrected bowel bag dose/volume measures (V45 Gy cc) may be used to predict acute bowel toxicity in patients receiving post-operative IMRT following a hysterectomy in endometrial and cervical cancers. Future studies will require validation in a larger patient population.D. Nganga: None. A. Hoover: None.

Abstract 2528: Rurality and neighborhood socioeconomic deprivation associated with patient-reported outcomes andsurvivalin men with prostate cancer in NRG RTOG 0415

Abstract Background: Prostate cancer is the most common cancer among men. Monitoring of patient-reported outcomes (PROs) can enhance provider-patient communication, promote better decision-making, and improve survival. Geospatial factors, namely rurality and neighborhood socioeconomic deprivation, could influence the experience across cancer treatment, thus impacting PROs and survival. This study examined associations of rurality, neighborhood socioeconomic deprivation (Area Deprivation Index [ADI]) with cancer treatment-related PROs and survival in men with prostate cancer. Methods: Data from men with prostate cancer in the trial NRG Oncology/RTOG 0415 were analyzed. In this trial, 1092 men were randomized to receive conventional radiotherapy (RT) or hypofractionated RT. Patients had Gleason scores of 2-6 and prostate-specific antigen of &amp;lt;10 ng/mL. Rurality was categorized as urban vs rural using Rural-Urban Continuum Codes via patient zip codes. Neighborhood socioeconomic deprivation was assessed by the ADI calculated via the American Community Survey by patient zip codes. The Expanded Prostate Cancer Index Composite (EPIC) measures cancer-specific quality of life (QOL); Hopkins Symptom Checklist measures anxiety and depression; EuroQoL-5 Dimension (EQ-5D) VAS and Index scores assess general health. All PROs were measured at baseline before and 6, 12, 24 and 60 months after RT. Overall survival (OS) and disease-free survival (DFS) were assessed using Cox proportional hazards models. Mixed effects models and generalized estimating equations were used to analyze PROs. Results: We analyzed 751 patients with complete data. Patients from the ADI 25% most deprived neighborhoods (vs. the other 75% of neighborhoods) were more likely to be non-white, unmarried and from rural areas. At baseline, patients from the most deprived areas had worse EPIC bowel score (P=0.011), worse sexual score (P=0.042) and worse hormonal score (P=0.015); patients from the most deprived areas had worse self-care (P=0.04) and more pain (P=0.047). Patients from rural areas had worse EPIC urinary score (P=0.03) and sexual score (P=0.003). Longitudinal analyses showed that ADI 25% most deprived areas (β=4.05, P=0.001) and rural areas (β=-5.70, P=0.003) were associated with worse EQ-5D VAS score. Compared to the 75% less deprived neighborhoods and urban, the ADI 25% most deprived neighborhoods and rural areas respectively had 47% (HR=1.466, P=0.033) and 93% (HR=1.925, P=0.026) relative increase in risk of recurrence or death (DFS). No differences were seen in OS. Conclusions: Patients with prostate cancer from the most deprived neighborhoods and rural areas had low QOL at baseline, poor general health and DFS. Interventions should target populations from socioeconomic deprived neighborhoods and rural areas to improve patient access to supportive care services and DFS. Citation Format: Jinbing Bai, Stephanie L. Pugh, Ronald Eldridge, Katherine Yeager, Qi Zhang, W Robert Lee, Amit B. Shah, Ian S. Dayes, David P. D'Souza, Jeff M. Michalski, Jason A. Efstathiou, John M. Longo, Thomas M. Pisansky, Jordan M. Maier, Sergio L. Faria, Anand B. Desai, Samantha A. Seaward, Howard M. Sandler, Mary E. Cooley, Deborah W. Bruner. Rurality and neighborhood socioeconomic deprivation associated with patient-reported outcomes andsurvivalin men with prostate cancer in NRG RTOG 0415 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2528.

Rectum Dose-Volume Histogram (DVH) Parameters And Patient-Reported EPIC-Bowel Domain For Patients Undergoing Radiotherapy (RT) For Prostate Cancer (PC): A Single-Center Prospective Registry Experience

Prostate cancer therapy toxicities can affect QOL. We report one of the first analyses of rectal dose and changes in QOL measured with the EPIC bowel domain in PC patients treated with curative intent RT in a large, single-institution prospective registry. Two hundred fifty-two pts with localized PC were treated with curative intent RT from 2016- 2018 on an IRB approved prospective registry. The Expanded Prostate Cancer Index Composite (EPIC) health-related QOL instrument was administered at baseline, end-of-treatment, 3, 6, 12 months (m), and then annually. A higher EPIC score implies less bowel symptom burden. DVH parameters for the rectal structure were computed, Dx was the dose (Gy) to a % of the rectum and Vx was the % volume receiving a given dose (Gy). Rectal dose was analyzed using BED (alpha/beta = 3), EQD2Gy, and total dose. In order to determine optimal cut-points to find clinically meaningful DVH, we utilized logistic regression and defined the ‘best’ cut-point to be the value that maximized Youden’s Index. Repeated measures mixed models were then implemented to determine the effect of patient, clinical, and treatment factors (including DVH) on patient-reported bowel symptom burden (EPIC-Bowel). Median follow-up was 20mo(range:2.5–40), pre-RT PSA = 6.12(1.3–129), T Stage T1c(T1b–T3b), Gleason Score 7(range 6-10), and 99% N0. The median prescribed dose was 70Gy (38–79.2) in 5 to 44 fractions. Standard fractionation (1.8-2Gy) was used in 120 pts (48.2%), moderate hypofractionation (2.5-3Gy) in 87 pts (35.1%), and extreme hypofractionation (>6Gy) in 42 pts (16.7%). Globally, treatment had minimal effect over EPIC-bowel scores which remained unchanged over time, with a median baseline = (96.4), end-of-treatment = (94.6), 3mo = (95.4), 6mo = (96.4), 12m = (94.6), and 24m = (96.4). However, rectal dose affected QOL with the strongest DVH signals noted for BED V51Gy and EQD2 V22Gy—with an optimal cut-point of 14.4% and 16.4%, respectively. On multivariate modeling BED V51Gy >14.4% was significantly associated with a decline of the epic bowel domain of 2.1 points (p = 0.01), and an EQD2 V22Gy >16.4% was significantly associated with a decline of 2.3 points (p<0.003). Rectal dose, specifically BED V51Gy>14.3% and EQD2 V22Gy>16.4%, are significantly associated with decline in bowel related QOL in patients undergoing definitive RT for localized PC. This is one of the first studies to examine rectal dose and correlate them to patient reported treatment related QOL.

Low-Dose-Rate Brachytherapy Combined With Ultrahypofractionated Radiation Therapy for Clinically Localized, Intermediate-Risk Prostate Cancer: Results From a Prospective Trial

To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer. This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months. The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure. Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial.

Focal ablation of apical prostate cancer lesions with irreversible electroporation (IRE).

To assess the safety, oncological and quality-of-life (QoL) outcomes of focal ablation of apical prostate cancer (PCa) lesions with irreversible electroporation (IRE). Patients were included in the study if they had a PCa lesion within 3mm of the apical capsule treated with IRE. The IRE procedure was performed in our institution by a single urologist. The QoL and functional data was collected prospectively from patients who provided consent using the Expanded Prostate Cancer Index Composite (EPIC). Oncological follow up included 3-month PSA levels, mpMRI at 6months and transperineal biopsy at 1-year post treatment. A total of 50 patients had apical PCa lesions treated between February 2013 and September 2018. Median follow-up was 44months. There were no Clavien-Dindo grade 3 events or higher. No perioperative complications were recorded. No significant difference was observed in the EPIC urinary or bowel QoL domain between baseline and 12-month post-treatment. One patient (2%) required one pad per day for urinary incontinence 12-month post-treatment. There was a small but significant decline in EPIC sexual QoL (65 at baseline and 59 at 12-month post-IRE). Of patient's potent pre-treatment, 94% remained potent after treatment. The median PSA nadir decreased by 71% (6.25-1.7ng/mL). Only one patient (2.5%) had in-field residual disease on repeat biopsy. Focal ablation using IRE for PCa in the distal apex appears safe and feasible with acceptable early QoL and oncologic outcomes.

Health-related quality of life by human immunodeficiency virus status in a cross-sectional survey of gay and bisexual prostate cancer survivors.

Prostate cancer is the most common invasive cancer in gay and bisexual men (GBM). Despite the unique sexual and urinary concerns of this group, studies of prostate cancer rehabilitation have primarily focused on heterosexual men. GBM also have high prevalence of human immunodeficiency virus (HIV), which may be associated with lower health-related quality of life (HRQOL). We examined the association between HIV status and HRQOL in a cohort of GBM with prostate cancer. Data from the Restore study, a cross-sectional online survey of GBM treated for prostate cancer, were used to examine this association. The Expanded Prostate Cancer Index Composite (EPIC) assessed function, bother, and summary measures in four domains: urinary, sexual, bowel, and hormone. Overall physical and mental HRQOL was assessed using the Short-Form Health Survey (SF-12). Multivariate analysis of variance and linear regression were used to evaluate the association between HIV status and HRQOL scores after adjustment for demographic and sexual characteristics. Of 192 participants, 24 (12.4%) reported an HIV diagnosis. After adjustment for covariates, HIV-positive status was associated with lower scores on the EPIC urinary (mean difference [MD]: -13.0, 95% CI, -21.4 to -4.6), sexual (MD: -12.5, 95% CI, -21.9 to -3.2), and bowel (MD: -5.9, 95% CI, -11.7 to -0.2) domains. No significant associations were observed between HIV status and other outcomes. HIV status may be associated with poorer urinary, sexual, and bowel HRQOL in GBM prostate cancer survivors.

A Phase II Study of Stereotactic Body Radiotherapy with Hydrogel Spacer for Prostate Cancer; Dosimetric Comparison, Acute Toxicity and Quality of Life

Volumetric modulated arc therapy (VMAT) stereotactic body radiotherapy (SBRT) with flattening filter-free (FFF) beam can achieve faster dose delivery and shorter treatment time for prostate cancer. A hydrogel spacer is used to reduce the rectal toxicity, but the clinical data of SBRT with hydrogel spacer are limited. The aim of this prospective single-center phase II study was to determine the efficacy and safety of FFF-VMAT SBRT combined with hydrogel spacer for localized prostate cancer. Men with localized prostate cancer were eligible for the study. A hydrogel spacer was inserted into the perirectal space between prostate and rectum before the initiation of SBRT. All patients underwent the planning CT scans before and after the spacer placement. Patients received 36.25 Gy to 95% of the PTV in 5 fractions every other day excluding weekends with 6MV single arc FFF-VMAT. The primary endpoint was acute toxicities during and within 3 months after the completion of SBRT. Toxicities were assessed using Common Terminology Criteria for Adverse Events v4.03. The secondary endpoints were International Prostate Symptom Score (IPSS) and quality of life (QOL) assessed by the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Target and normal tissue dosimetry were compared before and after the hydrogel spacer insertion. Between February 2017 and July 2018, forty patients with localized prostate cancer were enrolled. The median age was 70 years (55-79). Three, 25, 6, and 6 patients had low-, intermediate-, high-, and very high-risk prostate cancer according to the National Comprehensive Cancer Network (NCCN) risk classification. Twenty-three patients (58%) received concomitant androgen deprivation therapy. The hydrogel spacer placement was successful in 39 cases (98%). Seven (18%) and eighteen patients (45%) developed grade 2 acute gastrointestinal and genitourinary toxicities, respectively. No grade 3 acute toxicities were observed. Median IPSS temporarily increased at 2 weeks and 1 month after RT when compared to the pretreatment baseline (P < 0.05, 0.05, respectively), and returned to the baseline value in 3 months. EPIC urinary and bowel scores significantly declined at 2 weeks and 1 month after RT (P <0.05, 0.05, respectively), and no difference was observed at 3 months post-RT. Spacer use was associated with lower rectum dose for mean dose, maximum dose, and V100% to V50% (all P < 0.05). FFF-VMAT SBRT with a hydrogel spacer can be safely administered with acceptable acute toxicity. Hydrogel spacer insertion significantly reduced the dose to the rectum.

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy

ObjectiveWomen with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT. MethodsIn addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed. ResultsMean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT. ConclusionCorrelations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

5-Year Outcomes of a Prospective Phase 1/2 Study of Accelerated Hypofractionated Radiation Therapy to the Prostate Bed

PurposeTo report the 5-year outcomes from a single institution, prospective, phase 1/2 study on hypofractionated, accelerated radiation therapy to the prostate bed after radical prostatectomy. Methods and MaterialsPatients enrolled in this study were all eligible for postoperative radiation therapy and received a prescribed dose of 51 Gy in 17 fractions to the prostate bed. On follow-up, gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0; prostate-specific antigen (PSA) was evaluated and quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. ResultsA total of 30 patients were enrolled between 2008 and 2011. Median age was 65 (52-75) years. Median pretreatment PSA was 0.12 ng/mL (0.01-1.42). Twenty-six (93%) patients had Gleason ≤7 disease, 13 (43%) had pT3 disease, and 20 (67%) had positive margins. Twenty-six patients (87%) underwent radiation therapy as salvage treatment. After a median follow-up of 6.4 (2.1-8.1) years, no patient experienced Common Terminology Criteria for Adverse Events grade 3/4 toxicity. Eleven patients (37%) had grade 2 genitourinary and 2 (7%) had grade 2 gastrointestinal toxicity. At baseline and 5 years after radiation therapy, mean EPIC urinary domain score was 80% (standard deviation, 18%) and 82% (17%). Mean EPIC bowel domain score was 93% (13%) and 93% (15%). One patient (4%) had a minimally clinically important change in urinary domain score and 1 patient (4%) had a minimally clinically important change in bowel domain score. Nelson-Aalen estimated cumulative incidence of biochemical failure was 31% (nadir +0.2) and 18% (nadir +2.0) at 5 years. Four-year PSA ≥0.4 was predictive of subsequent androgen deprivation therapy use (Nelson-Aalen cumulative incidence: 1.45; P < .0001). Five patients (17%) received hormonal therapy for biochemical failure. Nelson-Aalen estimated cumulative incidence of hormone therapy use was 14% at 5 years. All patients who received hormone therapy had PSA >0.4 at 4 years. ConclusionsIn this phase 1/2 study, hypofractionated postoperative radiation therapy seems to have good clinical efficacy without significant late toxicity. Phase 3 studies are warranted.

A Phase 2 Randomized Pilot Study Comparing High-Dose-Rate Brachytherapy and Low-Dose-Rate Brachytherapy as Monotherapy in Localized Prostate Cancer

PurposeTo compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial. Methods and MaterialsMen with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples t test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted P value of ≤.05 was considered significant. ResultsLDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively; P = .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively; P = .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS (P = .003) and EPIC urinary irritative scores (P = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months; P = .028). ConclusionsHDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.

Quality of Life Outcome in Patients with Localized Prostate Cancer after Hypofractionatied Carbon-Ion Radiation Therapy

Carbon ion radiotherapy (C-ion RT) has excellent dose conformity and greater biological effectiveness than X-ray and proton beam. Moreover hypofractionatied schedule is better than conventional fractionated schedule to treat prostate cancer (PC) from the view point of biological aspect. The excellent outcome of C-ion RT for the patients with localized PC was already published. In our country, national health insurance has started to cover C-ion RT for localized PC since April 2018. Our hypothesis is that quality of life (QOL) outcome is maintained after hypofractionatied C-ion RT. The purpose of this study is to assess QOL outcome of the patients with localized PC received hypofractionatied C-ion RT. QOL outcome of 213 patients with localized PC received C-ion RT from August 2013 to July 2014 were analyzed. The prescribed dose of the C-ion RT was 51.6 Gy (RBE) in 12 fractions in 3 weeks. The median age at the time of the C-ion RT was 68 (range 46-88). The number of the patients of low, intermediate and high risk according to D’Amico criteria were 28 (13.1%), 82 (38.5%) and 103 (48.4%), respectively. Out of the 213 patients, 186 patients (87.3%) received hormonal therapy (HT). Two QOL assessment questionnaires of International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) were used at 6 points; before the C-ion RT, the last day of the C-ion RT, and 6, 12, 24 and 36 months after the C-ion RT. Among a subgroup of the 23 low risk patients not received any HT, the EPIC sexual domain was assessed in addition. The median follow-up time was 38.3 months (range 0.7-52.1). At the time of this analysis, 9 patients recurred and no patient experienced grade 3 and worse adverse event. The EPIC scores were available for 97.7%, 90.6%, 86.9%, 85.0%, 80.8% and 75.1% at the 6 points as above, respectively. The average IPSS and EPIC scores of the analyzed 213 patients are noted in the table. The IPSS score and the EPIC urinary score worsened temporarily during the C-ion RT and recovered to the baseline level. The EPIC bowel, sexual and hormonal scores did not change. The EPIC sexual scores of the subgroup of the 23 low risk patients not received any HT are also noted in the table, the score slightly worsened temporarily during the C-ion RT and recovered to the baseline level.Abstract SU_35_2341; Table 1The average scores of IPSS and EPICBefore the C-ion RTThe last day of the C-ion RT6 months12 months24 months36 monthsIPSS7.912.26.76.75.32.6EPICUrinary91.584.691.691.792.493.6Bowel93.892.394.194.592.794.2Sexual33.332.835.136.037.538.8(subgroup*Twenty-three low-risk patients not received any HT.)43.741.346.945.447.644.2Hormonal83.384.385.788.791.093.0∗ Twenty-three low-risk patients not received any HT. Open table in a new tab It is suggested that the QOL outcome of the patients with localized PC is well maintained after the hypofractionatied C-ion RT. Further studies are required to asses QOL outcome more precisely especially sexual function because most patients in this analysis received HT.

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes

BackgroundWe report prospectively captured clinical toxicity and patient reported outcomes in a single institutional cohort of patients treated for prostate cancer with proton beam therapy (PBT). This is the largest reported series of patients treated mostly with pencil beam scanning PBT.MethodsWe reviewed 231 patients treated on an IRB approved institutional registry from 2013 to 2016; final analysis included 192 patients with > 1-year of follow-up. Toxicity incidence was prospectively captured and scored using CTCAE v4.0. International Prostate Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) score, and Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires were collected at each visit. Univariate Cox regression was used to explore associations of grade 2+ toxicity with clinical, treatment, and dosimetric variables.ResultsMedian follow-up was 1.7 years. Grade 3 toxicity was seen in 5/192 patients. No grade 4 or 5 toxicity was seen. Patient reported quality-of-life showed no change in urinary function post-radiation by IPSS scores. Median SHIM scores declined by 3.7 points at 1-year post-treatment without further decrease beyond year 1. On univariate analysis, only younger age (HR = 0.61, p = 0.022) was associated with decreased sexual toxicity. EPIC bowel domain scores declined from 96 at baseline (median) by an average of 5.4 points at 1-year post-treatment (95% CI: 2.5–8.2 points, p < 0.001), with no further decrease over time. Bowel toxicity was mostly in the form of transient rectal bleeding and was associated with anticoagulation use (HR = 3.45, p = 0.002).ConclusionsGrade 3 or higher toxicity was rare at 2-years after treatment with PBT for localized prostate cancer. Longer follow-up is needed to further characterize late toxicity and biochemical control.Trial registrationNCT, NCT01255748. Registered 1 January 2013.

Analysis of Gastrointestinal Toxicity in Patients Receiving Proton Beam Therapy for Prostate Cancer: A Single-Institution Experience

PurposeWe characterized both physician- and patient-reported rates of gastrointestinal (GI) toxicity in patients treated with proton beam therapy (PBT) at our institution for prostate adenocarcinoma and identified factors associated with toxicity. Methods and materialsWe treated 192 patients with PBT between July 2013 and July 2016. Included patients had ≥1 year of follow-up. Potential preexisting clinical and treatment-related risk factors for GI toxicity were recorded. Common Terminology Criteria for Adverse Events version 4.0 was used to score toxicity. Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires assessed patient-reported quality of life. Associations between grade (GR) 2+ toxicity and clinical, treatment, and dosimetric factors were assessed using Cox models and corresponding hazard ratios. ResultsThe median follow-up was 1.7 years. Most of the observed GI toxicity (>90%) was in the form of rectal bleeding (RB). GR2+ GI toxicity and RB actuarial rates specifically at 2 years were 21.3% and 20.4%, respectively. GR3 toxicity was rare, with only 1 observed RB event. No GR4/5 toxicity was seen. The EPIC bowel domain median score was 96 (range, 61-100) pretreatment, 93 (range, 41-100) at 1 year, 89 (range, 57-100) at 1.5 years, and 89 (range, 50-100) at 2 years. Anticoagulation use was the only factor selected during multivariate analysis for predicting GR2+ RB, with a resulting concordance index of 0.59 (95% confidence interval, 0.48-0.68; P = .088). Type of proton technology (pencil beam scanning vs uniform scanning) and number of fields treated per day (1 vs 2) showed no significant difference in toxicity rate. ConclusionsPBT was associated with acceptable rates of GR2+ transient GI toxicity, mostly in the form of RB, which correlated with anticoagulation use. High EPIC bowel domain quality of life was maintained in the 2 years after treatment.

Health-related-quality-of-life and toxicity after single fraction 19 Gy high-dose-rate prostate brachytherapy: Phase II trial

PurposeTo evaluate the safety, tolerance and impact on health-related-quality-of-life (HRQoL) of the high-dose-rate brachytherapy of 19 Gy (BRT-HDR-19 Gy) single fraction in prostate cancer. MethodsFrom January 2014 to July 2016, 43 patients with low/intermediate risk were treated with BRT-HDR-19 Gy. The patients were monitored prospectively for toxicity and HRQoL. ResultsThe median age, initial PSA and the International Prostate Symptom Score (IPSS) were 71 years (55–78), 7.0 ng/mL (4.2–17.8) and 5 (0–14) respectively. 44% were low-risk and 56% intermediate-risk. Median CTV-V100 (where Vn is the fractional volume of the organ that receives n% of the prescribed dose) was 96.5%, Urethral-Dmax 106% and rectum-2 cc (the dose to 2 cc of rectal wall) 53%. After a median follow-up of 20 months (4–26), acute grade-2 genitourinary (GU) toxicity occurred in 4 patients (9%) and none presented acute gastrointestinal (GI) toxicity. Similarly, four patients (9%) presented late GU grade-2 toxicity. No grade-3 toxicity occurred.In terms of HRQoL, there was a statistically significant decline in Expanded Prostate Cancer Index Composite (EPIC) urinary urgency/obstructive domain at month 3 (p = 0.047), and returned to baseline by month 6. Mean EPIC urinary incontinence, bowel, sexual and hormonal domains did not present significant post BRT-HDR-19 Gy changes.Patients rated their satisfaction at 6 months as “very-satisfied” (23%) or “extremely-satisfied” (77%). ConclusionsBRT-HDR-19 Gy demonstrates excellent results in terms of toxicity, tolerance, safety, patient satisfaction and HRQoL.

Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer.

To evaluate the feasibility, safety, early quality-of-life (QoL) and oncological outcomes of salvage focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa). Patients with localized, radio-recurrent PCa without evidence of metastatic or nodal disease were offered focal IRE according to the consensus guidelines. Patients with a minimum follow-up of 6months were eligible for analysis. Adverse events were monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Patient-reported QoL data were collected at baseline, 6weeks, 3, 6 and 12months using the Expanded Prostate Cancer Index Composite (EPIC), the American Urological Association (AUA) symptom score and the 12-item short-from health survey (SF-12) physical and mental component summary questionnaires. Oncological control was evaluated according to serial prostate-specific antigen (PSA), 6-month multiparametric magnetic resonance imaging (mpMRI) and 12-month prostate biopsy. Wilcoxon's signed rank test was used to assess QoL differences over time in paired continuous variables. A total of 18 patients were included in the analysis. The median follow-up was 21months. No high-grade adverse events (CTCAE >2) or recto-urethral fistulae occurred. No statistically significant declines were observed in QoL outcomes (n = 11) on the EPIC bowel domain (P = 0.29), AUA symptom score (P = 0.77), or the SF-12 physical (P = 0.17) or SF-12 mental component summary (P = 0.77) questionnaires. At 6months, patients who had undergone salvage therapy experienced a decline in EPIC sexual domain score (median of 38-24; P = 0.028) and urinary domain (median of 96-92; P = 0.074). Pad-free continence and erections sufficient for intercourse were preserved in 8/11 patients and 2/6 patients at 6months, respectively. The mpMRI was clear in 11/13 patients, with two single out-field lesions (true-positive and false-positive, respectively). The median (interquartile range) nadir PSA was 0.39 (0.04-0.43)μg/L. Three and four patients experienced biochemical failure using the Phoenix and Stuttgart definitions of biochemical failure, respectively. Eight out of 10 of the patients were clear of any PCa on follow-up biopsy, whereas two patients had significant PCa on follow-up biopsy (International Society of Urological Pathology grade 5). Our short-term safety, QoL and oncological control data show that focal IRE is a feasible salvage option for localized radio-recurrent PCa. A prospective multicentre study (FIRE trial) has been initiated that will provide further insight into the ability of focal IRE to obtain oncological control of radio-recurrent PCa with acceptable patient morbidity.