Expanded Prostate Cancer Index Composite Research Articles

Efficacy of a hydrogel spacer for improving quality of life in patients with prostate cancer undergoing low-dose-rate brachytherapy alone or in combination with intensity-modulated radiotherapy: An observational study using propensity score matching.

It is unclear whether a hydrogel spacer can improve quality of life (QOL) in patients undergoing low-dose-rate brachytherapy (LDR-BT) alone or in combination with intensity-modulated radiotherapy (IMRT). We enrolled patients with prostate cancer who underwent LDR-BT alone with (n = 186) or without (n = 348) a hydrogel spacer, or underwent LDR-BT in combination with IMRT with (n = 70) or without (n = 217) a hydrogel spacer. QOL was evaluated using Expanded Prostate Cancer Index Composite (EPIC) questionnaires at baseline and 1, 3, 6, 12, and 24 months after implantation. The groups were compared using propensity score matching analysis. Among patients who underwent LDR-BT alone, there were no differences regarding changes in urinary, bowel, sexual, or hormonal domain scores between the spacer and no-spacer groups; however, the dose at the bowel was significantly lower in the spacer group than in the no-spacer group. Among patients who underwent LDR-BT in combination with IMRT, there were no differences regarding changes in urinary, sexual, or hormonal domain scores between the spacer and no-spacer groups. However, the changes in the bowel domain score were significantly lower in the spacer group than in the no-spacer group (p < 0.001). A hydrogel spacer may not improve impaired urinary, bowel, or sexual QOL in patients undergoing LDR-BT alone. However, in patients undergoing LDR-BT in combination with IMRT, a hydrogel spacer can improve impaired bowel QOL but not sexual or urinary QOL.

Perioperative, Oncological, and Functional Outcomes Between Robot-Assisted Laparoscopic Prostatectomy and Open Radical Retropubic Prostatectomy: A Randomized Clinical Trial.

Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting. In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months. From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms. Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months.

A 3‐month mark to urinary continence, after robotic radical prostatectomy—Is it possible?

AbstractIntroduction and ObjectivesUrinary incontinence (UI) remains a significant concern after radical prostatectomy. As a part of a nursing follow‐up, we evaluate quality‐of‐life (QoL) which includes UI recovery. Patients proposed to Retzius‐sparing robot assisted radical prostatectomy (RS‐RARP) have a bundle of appointments starting pre‐operatively and continuing after surgery 1 week, 1, 3, 6, 9 and 12 months. In these, we started a urinary rehabilitation programme (URP) performing Kegel Exercises, adaptative and behavioural strategies. The objective is to evaluate timeline until urinary continence recovery after RS‐RARP, since this is one of the most asked question by our patients.Materials and MethodsBetween July 2017 and April 2020 we conducted a prospective observational single‐centre study with a total of 208 patients submitted to RS‐RARP. We applied the Expanded Prostate Cancer Index Composite‐26 (EPIC‐26) questionnaire pre and postoperatively at 3, 6, 9 and 12 months, and studied UI by evaluating pad count measured in the 3rd question. The inclusion criteria are: patients that did not have adjuvant or salvage treatments during the follow up; have all pre‐ and post‐operative evaluations; who were continent pre‐operatively; and started the URP. A total of 72 patients were included. We have considered the criteria of no pad use for continence recovery. Every patient provided written informed consent for study inclusion, approved by the Institutional Ethics Committee (Approval 07.07.2017).ResultsPreliminary analysis of enrolled patients reveals that 57 (79,16%) recovered continence during the 12 months period. By 3‐month mark, we observed that 42 (73,68%) patients were continent; 7 (12,28%) recovered continence at 6‐month mark; 4 (7,02%) recovered continence at 9‐month mark and 4 (7,02%) recovered continence 1 year after surgery. We further analysed the total number of pads used daily by the 15 patients (20,83%) that had UI at 12‐month mark: 13 patients (86,67%) reported using 1 pad a day and 2 patients (13,33% or 2,77% of all studied population) reported using 3 or more pads a day.ConclusionThe preliminary results demonstrate a gradual improvement in UI over the first year, with a significant number of patients recovering at 3‐month mark. These positive results are most probably consequences of both the surgical approach and the URP. Is required a sub‐group analysis to further delineate factors impacting continence recovery, aiding in postoperative rehabilitation care plans that will impact positive outcome on QoL associated with a fast UI recovery. For the latter, digital tools to conduct patient reported outcomes are necessary to ascertain the extent of impact in QoL. Furthermore, we need to rethink remote strategies to improve patient compliance as a significant number of them were excluded for not attending on‐site nursing appointments.

Physiotherapy for continence and muscle function in prostatectomy: a randomised controlled trial.

To assess the effectiveness of pre- and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot-assisted laparoscopic radical prostatectomy (RARP). We carried out a single-blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24-h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0-908.0] g vs 21.0 [0.0-750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24-h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra-anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP.

Comparison of sexual function after robot-assisted radical prostatectomy and carbon-ion radiotherapy for Japanese prostate cancer patients using propensity score matching

BackgroundThe quality of life of patients is an important consideration when selecting treatments for localized prostate cancer (PCa). We retrospectively compared sexual function after robot-assisted radical prostatectomy (RARP) and carbon-ion radiotherapy (CIRT) using propensity score matching.MethodsIn total, 127 Japanese PCa patients treated with RARP and 190 treated with CIRT monotherapy were evaluated. We evaluated the Expanded Prostate Cancer Index Composite (EPIC) score before treatment and 12 and 24 months after treatment. After propensity score matching, data from 101 patients from each group were analyzed. The study protocol was approved by the Institutional Review Board of Gunma University Hospital (no. IRB2020-050, 1839).ResultsAfter propensity score matching, the mean EPIC sexual function summary scores in the RARP and CIRT groups were 46.4 and 48.2, respectively. At 12 and 24 months after treatment, these scores were 27.9 (39.9% decrease) and 28.2 (39.2% decrease) in the RARP group and 41.4 (14.1% decrease) and 41.6 (13.7% decrease) in the CIRT group, respectively. Both groups demonstrated significantly decreased scores after 12 and 24 months of treatment compared to before treatment (all p < 0.05). At 12 and 24 months, the sexual function summary score was significantly higher in the CIRT group than in the RARP group (p < 0.001).ConclusionsThere was a smaller decrease in the EPIC sexual function score in the CIRT group than in the RARP group. These results provide useful information for treatment decision-making of Japanese PCa patients.

Six-Month Prostate Cancer Empowerment Program (PC-PEP) Improves Urinary Function: A Randomized Trial.

Purpose: This is a secondary analysis examining a six-month home-based Prostate Cancer-Patient Empowerment Program (PC-PEP) on patient-reported urinary, bowel, sexual, and hormonal function in men with curative prostate cancer (PC) against standard of care. Methods: In a crossover clinical trial, 128 men scheduled for PC surgery (n = 62) or radiotherapy with/without hormones (n = 66) were randomized to PC-PEP (n = 66) or waitlist-control and received the standard of care for 6 months, and then PC-PEP to the end of the year. PC-PEP included daily emails with video instructions, aerobic and strength training, dietary guidance, stress management, and social support, with an initial PFMT nurse consultation. Over 6 months, participants in the PC-PEP received optional text alerts (up to three times daily) reminding them to follow the PFMT video program, encompassing relaxation, quick-twitch, and endurance exercises; compliance was assessed weekly. Participants completed baseline, 6, and 12-month International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Results: At 6 months, men in the PC-PEP reported improved urinary bother (IPSS, p = 0.004), continence (EPIC, p < 0.001), and irritation/obstruction function (p = 0.008) compared to controls, with sustained urinary continence benefits at 12 months (p = 0.002). Surgery patients in the waitlist-control group had 3.5 (95% CI: 1.2, 10, p = 0.024) times and 2.3 (95% CI: 0.82, 6.7, p = 0.11) times higher odds of moderate to severe urinary problems compared to PC-PEP at 6 and 12 months, respectively. Conclusions: PC-PEP significantly improves lower urinary tract symptoms, affirming its suitability for clinical integration alongside established mental health benefits in men with curative prostate cancer.

One-year clinical outcomes of MR-guided stereotactic body radiation therapy with rectal spacer for patients with localized prostate cancer

Background and purposeThis prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes.Materials and methodsThirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1–3 months), subacute (4–12 months), and late (> 12 months) phases.ResultsThe median follow-up was 390 days (range 28–823) and the median age was 70 years (range 58–82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6–15.3), and the median length of the spacer was 45.9 mm (range 16.8–62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4–99.8] for spacer vs. 97.8% [range 69.6–99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0–4.6] for spacer vs. 4.9 cc [range 0–12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains.ConclusionsMRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.

Converting between the International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite (EPIC) urinary subscales: modeling and external validation

BackgroundProstate-related quality of life can be assessed with a variety of different questionnaires. The 50-item Expanded Prostate Cancer Index Composite (EPIC) and the International Prostate Symptom Score (IPSS) are two widely used options. The goal of this study was, therefore, to develop and validate a model that is able to convert between the EPIC and the IPSS to enable comparisons across different studies.MethodsThree hundred forty-seven consecutive patients who had previously received radiotherapy and surgery for prostate cancer at two institutions in Switzerland and Germany were contacted via mail and instructed to complete both questionnaires. The Swiss cohort was used to train and internally validate different machine learning models using fourfold cross-validation. The German cohort was used for external validation.ResultsConverting between the EPIC Urinary Irritative/Obstructive subscale and the IPSS using linear regressions resulted in mean absolute errors (MAEs) of 3.88 and 6.12, which is below the respective previously published minimal important differences (MIDs) of 5.2 and 10 points. Converting between the EPIC Urinary Summary and the IPSS was less accurate with MAEs of 5.13 and 10.45, similar to the MIDs. More complex model architectures did not result in improved performance in this study. The study was limited to the German versions of the respective questionnaires.ConclusionsLinear regressions can be used to convert between the IPSS and the EPIC Urinary subscales. While the equations obtained in this study can be used to compare results across clinical trials, they should not be used to inform clinical decision-making in individual patients.Trial registrationThis study was retrospectively registered on clinicaltrials.gov on January 14th, 2022, under the registration number NCT05192876.

External validation of predictive models of sexual, urinary, bowel and hormonal function after surgery in prostate cancer subjects

BackgroundIn 2020, a research group published five linear longitudinal models, predict Expanded Prostate Cancer Index Composite-26 (EPIC-26) scores post-treatment for radical prostatectomy, external beam radiotherapy and active surveillance collectively in US patients with localized prostate cancer.MethodsOur study externally validates the five prediction models for patient reported outcomes post-surgery for localised prostate cancer. The models’ calibration, fit, variance explained and discrimination (concordance-indices) were assessed. Two Australian validation cohorts 1 and 2 years post-prostatectomy were constructed, consisting of 669 and 439 subjects, respectively (750 in total). Patient reported function in five domains post-prostatectomy: sexual, bowel, hormonal, urinary incontinence and other urinary dysfunction (irritation/obstruction). Domain function was assessed using the EPIC-26 questionnaire.Results1 year post-surgery, R2 was highest for the sexual domain (35%, SD = 0.02), lower for the bowel (21%, SD = 0.03) and hormone (15%, SD = 0.03) domains, and close to zero for urinary incontinence (1%, SD = 0.01) and irritation/obstruction (− 5%, SD = 0.04). Calibration slopes for these five models were 1.04 (SD = 0.04), 0.84 (SD = 0.06), 0.85 (SD = 0.06), 1.16 (SD = 0.13) and 0.45 (SD = 0.04), respectively. Calibration-in-the-large values were − 2.2 (SD = 0.6), 2.1 (SD = 0.01), 5.1 (SD = 0.1), 9.6 (SD = 0.9) and 4.0 (SD = 0.2), respectively. Concordance-indices were 0.73, 0.70, 0.70, 0.58 and 0.62, respectively (all had SD = 0.01). Mean absolute error and root mean square error were similar across the validation and development cohorts. The validation measures were largely similar at 2 years post-surgery.ConclusionsThe sexual, bowel and hormone domain models validated well and show promise for accurately predicting patient reported outcomes in a non-US surgical population. The urinary domain models validated poorly and may require recalibration or revision.

A pooled patient-reported outcomes analysis of moderately hypofractionated proton beam therapy and photon-based intensity modulated radiation therapy for low- or intermediate-risk prostate cancer.

We sought to characterize and compare late patient-reported outcomes (PROs) after moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) for localized prostate cancer (PC). This multi-institutional analysis included low- or intermediate-risk group PC patients treated with moderately hypofractionated radiation to an intact prostate stratified by treatment modality: IMRT or PBT. The primary outcomes were prospectively collected patient-reported late gastrointestinal (GI) and genitourinary (GU) toxicity assessed by International Prostate Symptom Score (IPSS) and Expanded PC Index Composite (EPIC). Multivariable regression analysis (MVA) controlling for age, race, and risk group tested the effect of time, treatment, and their interaction. 287 IMRT and 485 PBT patients were included. Intermediate risk group (81.2 vs. 68.2%; p < 0.001) and median age at diagnosis (70 vs. 67 years; p < 0.001) were higher in the IMRT group. On MVA, there was no significant difference between modalities. PBT IPSS did not differ from IMRT IPSS at 12 months (odds ratio [OR], 1.19; p = 0.08) or 24 months (OR, 0.99; p = 0.94). PBT EPIC overall GI function at 12 months (OR, 3.68; p = 0.085) and 24 months (OR 2.78; p = 0.26) did not differ from IMRT EPIC overall GI function. At 24 months, urinary frequency was no different between PBT and IMRT groups (OR 0.35; p = 0.096). This multi-institutional analysis of low- or intermediate-risk PC treated with moderately hypofractionated PBT and IMRT demonstrated low rates of late patient-reported GI and GU toxicities. After covariate adjustment, late GI and GU PROs were not significantly different between PBT or IMRT cohorts.

Psychometric validation of the Spanish version of the Expanded Prostate Cancer Index Composite-26

PurposeTo assess the validity, reliability, and responsiveness of the Spanish version of the Expanded Prostate cancer Index Composite (EPIC) with 26 items.MethodsMulticentric longitudinal study of patients diagnosed with localized or locally advanced prostate cancer (any T, any N, M0) treated with active surveillance, surgery, external radiotherapy, or brachytherapy. The EPIC-50 was administered initially to the cohort (n = 324 patients), until it was replaced in November 2019 by the EPIC-26 (n = 543), in both groups before treatment and 12 months after. We assessed confirmatory factor analysis (CFA), reliability with Cronbach’s alpha coefficient, criterion validity with the intraclass correlation coefficient (ICC), and responsiveness by testing a priori hypotheses on deterioration effect size (ES).ResultsThe CFA confirmed the five-domain structure of the EPIC-26 proposed by the original instrument (comparative fit index = 0.95). The agreement between EPIC-50 (gold standard) and EPIC-26 domains was excellent (ICC > 0.90). Cronbach’s alpha was > 0.7 in almost all domains, and the floor effect was near zero, although ceiling effect was higher than 50% in urinary incontinence and bowel domains. Hypothesized changes between before and 12 months after treatment were confirmed: ES > 0.8 in both urinary incontinence and sexual domains among patients who underwent surgery; and ES ranging 0.44–0.48 for bowel and sexual domains in patients treated with external radiotherapy.ConclusionThe Spanish version of the EPIC-26 has demonstrated adequate metric properties, similar to those of the original version, with acceptable goodness-of-fit indices, good criterion validity, reliability, and responsiveness to detect changes after radical prostatectomy or external radiotherapy.

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands

PurposeHistorically, toxicity concerns have existed in patients with large prostate glands treated with radiotherapy (RT), particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. Methods and MaterialsWe retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging (MRI). Toxicity was measured using CTCAE version 5.0. Many patients received the Expanded Prostate Cancer Index Composite (EPIC) Quality of Life (QOL) questionnaires. Minimum follow-up (FU) was 2 years. ResultsSeventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500-3625 cGy in 5 fractions. A minority (27%) received ADT, which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction prior to RT. Median toxicity FU was 4.0 years. Two-year rates of Grade 1+ genitourinary (GU), Grade 1+ gastrointestinal (GI), and Grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total Grade 3 GU toxicities were very limited (2.8%). There were no Grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of Grade 2+ GU toxicity (OR = 3.19, p = 0.024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, QOL, or oncologic outcomes. ConclusionsWith early FU, ultra-large prostate glands do not portend increased risk of high-grade toxicity following SBRT but likely carry an elevated risk of low-grade GU toxicity.

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.

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 randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT)

BackgroundUltra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT–utilizing potentially fewer treatments–is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment.Methods/DesignA total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10–14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7–10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score.DiscussionFORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa.Trial registrationClinicaltrials.gov identifier: NCT04984343. Date of registration: July 30, 2021.Protocol version: 4.0, Nov 8, 2022.

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.

Health-Related Quality of Life at Five Years for a Randomized Trial of Tri-Modality Therapy with I-125 Brachytherapy, External Beam Radiation Therapy, and Short- vs. Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer (TRIP)

To describe the patient-reported health-related quality of life (HR-QoL) outcomes at five years for a multicenter randomized trial of tri-modality therapy with iodine-125 brachytherapy, external beam radiation therapy (EBRT), and short- versus long-term androgen deprivation therapy (ADT) for high-risk localized prostate cancer (TRIP/TRIGU0907). A total of 332 men with high-risk prostate cancer were randomized to either 6 months of ADT (n = 165) or 30 months of ADT (n = 167) in conjunction with combined modality radiation therapy. For the HR-QoL assessment, general HR-QoL and disease-specific HR-QoL were measured using the Japanese version of the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite (EPIC). Patient-reported outcome questionnaires were filled out before ADT initiation, and five years after. Scores were reported as mean with the standard deviation. QoL end points were assessed as the change between pre and post treatment using paired student t-test. Changes in the International Prostate Symptom Scores (IPSS) score, including total score and subscores, were also evaluated. The study was powered according to the primary endpoint of biochemical progression free survival with HR-QoL as a secondary endpoint. In addition, recovery of testosterone level (300ng/dL or higher) was calculated as the cumulative incidence curve and compared between arms by log-rank test. The cumulative incidence of biochemical progression, and salvage ADT treatment were not different between the arms. Mean domain scores at baseline were well balanced between the two arms in all HR-QoL. There were no differences in the SF-8 assessment and the total and subscore EPIC assessments between the arms. The average sexual function score was lower in short arm versus long arm; 16.24 versus 20.24 at baseline, but not different at five years, 9.96 versus 7.78 (p = 0.164). There were no significant differences between the arms for the total and subscore IPSS. Significantly higher percentage of patients, 71.7% in the short arm recovered to a normal testosterone level at 6 years after the initiation of ADT compared to 43.2% in long arm (p<0.0001). At five years after ADT initiation, there were no significant differences in all score changes between the two arms with general HR-QoL and disease-specific HR-QoL. Most of HR-QoL returned to baseline level, and sexual function scores were low from baseline in this population. Two-years' adjuvant ADT did not affect HR-QoL at five years, although it significantly retarded testosterone recovery compared to 6 months of hormone therapy.

Long-Term Urinary Toxicity Follow-Up of Combined External Beam Radiation and Cs-131 LDR Brachytherapy Boost for Prostate Cancer

To evaluate and update our institutional data on chronic patient-reported urinary symptoms in patients with prostate cancer treated with combined external beam radiation therapy (EBRT) and Cesium-131 (Cs-131) LDR brachytherapy boost. Patients treated from September 2006-July 2022 and with at least 6 months of follow-up were analyzed. Patients filled out the Expanded Prostate Cancer Index Composite (EPIC) questionnaire pre-treatment and at each scheduled follow-up. Mean EPIC urinary scores were calculated for urinary summary, urinary function, urinary bother, urinary incontinence, and urinary irritative/obstructive domains. Changes of 7-points or more in mean domain scores were deemed clinically significant. The prevalence of urinary bleeding was calculated and bleeding occurring more than "about once a week" ("more than once a week", "about once a day", and "more than once a day") was deemed clinically significant. Outcomes were analyzed at each follow-up timepoint using paired t-test. A total of 341 patients with prostate cancer were included in the analysis of which 183 were intermediate-risk and 158 high-risk. 174 patients were treated with tri-modality therapy, and SpaceOAR was used in 108 patients. Long-term statistically significant decreases in mean EPIC QOL scores were seen in urinary summary, urinary function, urinary bother, urinary incontinence, and urinary irritative/obstructive domains at 6 months, with clinically and statistically significant decreases in urinary function and urinary incontinence at 6 months (86±17.4, 83.4±22.2 respectively) and up to 18 months post-treatment (84.8±17.4, 83.6±20.7 respectively) compared with pre-treatment scores (93.1±10.7, 90.8±14.8 respectively), with both domains returning to clinical baseline at 24 months. Urinary irritative/obstructive mean scores clinically and significantly decreased at 9 months (77±17.4) compared to pre-treatment (84.7±13.5), returning to clinical baseline at 12 months. The prevalence of clinically significant urinary bleeding at 6, 12, 24, 36, 48, and 60 months was 1.3%, 2.6%, 3.7%, 0.7%, 0.9%, and 2.3% respectively. At the median follow-up of 42 months (IQR 54, 18-72), mean EPIC scores were clinically improved (≥7-point increase) from pre-treatment baseline in 15-30% of patients across the analyzed urinary domains. Long-term patient-reported clinically significant decreases in urinary function and urinary incontinence mean EPIC scores occurred up to 18 months following combined external beam radiation and Cs-131 prostate brachytherapy and returned to baseline at 24 months, while clinically significant decrease in urinary irritability/obstructive mean scores occurred at 9 months and returned to baseline at 12 months. At 42 months follow-up, mean urinary domain scores improved from pre-treatment baseline in 15-30% of patients.

Quality of Life Results of Addition of Androgen Deprivation Therapy and Pelvic Lymph Node Treatment to Prostate Bed Salvage Radiotherapy: NRG Oncology/RTOG 0534 SPPORT

Report the quality of life (QOL) analysis of the SPPORT trial of men with a detectable prostate specific antigen (PSA) after prostatectomy for prostate cancer randomized to (Arm 1) salvage prostate bed radiotherapy (PBRT), (Arm 2) 4-6 months of short-term androgen deprivation therapy (STADT) + PBRT, and (Arm 3) pelvic lymph node radiotherapy (PLNRT) + STADT + PBRT. Primary analysis established a benefit of adding PLNRT and STADT to PBRT. There was higher short term but no statistically significant difference in long term adverse events with the exception of blood or bone marrow events. QOL endpoints were assessed at baseline, 6 weeks after RT start, 1 and 5 years, including Expanded Prostate Cancer Index Composite (EPIC) (bowel, urinary, sexual, and hormonal domains), Hopkins Symptom Checklist (HSCL-25) (depressive symptoms), and the EuroQol (EQ-5D) (health state weights used in quality adjusted life years (QALYs). In addition to statistical significance, differences in scores were assessed using 0.5 standard deviation (SD) as the criterion for clinical importance. Difference among arms was assessed using pairwise t-tests, Fisher's exact test, and mixed effects regression modeling. To control for multiplicity, the p-value required for statistical significance is p<0.025. Six hundred forty-four patients consented to QOL, about 210 on each arm. Baseline characteristics were not significantly different among arms: 81% were white and 54% <65 years. For EPIC, bowel domain scores decreased at 6 weeks post-RT then increased by years 1 and 5, although not to baseline levels. One clinically significant difference in bowel scores was Arm 3 vs. Arm 1 at 6 weeks. For the urinary domain, scores decreased at 6 weeks post-RT and remained below baseline at 1 and 5 years, but there were no significant differences among arms. For the sexual domain, there were statistically significant differences between arms at 6 weeks and 1 year with patients receiving STADT exhibiting poorer sexual QOL scores. By year 5 the differences were no longer significant. A similar pattern was seen for the hormonal domain. For HSCL-25, differences at 6 weeks were statistically but not clinically significant, and there were no significant differences at the later time points. Comparisons of QALYs for overall survival over an 8-year horizon showed no significant group differences, with a mean of about 7.8 in each arm. Regarding freedom from progression, QALY means were 5.7, 6.5, and 7.4 years for Arms 1, 2, and 3, respectively, with a significant difference between Arms 3 and 1 (p = <.001) favoring the more intensive treatment. While QOL generally declined among all arms at 6 weeks post RT, there were no clinically significant differences in QOL among arms at 5 years. QALYs for freedom from progression favored STADT + PLNRT + PBRT for salvage treatment of prostate cancer.

Impact of postoperative sexual function on health-related quality of life after robot-assisted radical prostatectomy

Abstract Background We investigated potential disparities in health-related quality of life, particularly concerning urinary function, between patients with preserved and those with impaired sexual function after robot-assisted radical prostatectomy (RARP). Materials and methods Between December 2012 and April 2020, 704 men underwent RARP in our hospital. This study included 155 patients with a preoperative 5-item International Index of Erectile Function (IIEF-5) of ≥12 points and an assessable IIEF-5 at 12 months postoperatively. Health-related quality of life was assessed using the 8-item Short-Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC) preoperatively and at 3, 6, and 12 months postoperatively. A logistic regression analysis and Wilcoxon rank sum tests were performed. Results Patients were grouped according to the median IIEF-5 score 12 months after surgery: those with preserved sexual function (n = 71) and those with impaired sexual function (n = 84). The mental component summary of the 8-item Short-Form Health Survey was better in the group with preserved sexual function at 6 months postoperatively than in the group with impaired sexual function (p &lt; 0.01). In the EPIC, the group with preserved sexual function performed better not only in the sexual domain but also in the urinary domain at all time points compared with the group with impaired sexual function (p &lt; 0.01). In the comparison of the urinary subdomains of the EPIC, there were no significant differences in urinary function or incontinence, but there were significant differences in urinary distress and irritative/obstructive scores (p &lt; 0.01). Conclusions Patients with preserved postoperative sexual function after RARP showed better urinary function than those with impaired sexual function. Hence, preserved sexual function is closely associated with urinary function.