Radiotherapy For Prostate Cancer Research Articles

Update from the PSMA-dRT trial: A randomized phase III trial of PSMA-PET prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer.

291 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior diagnostic accuracy for detecting regional and distant metastases compared to conventional imaging (CT, bone scan, and MRI) in men with prostate cancer. This has the potential to guide definitive radiation therapy (dRT) patient selection and planning. Whether the use of improved diagnostic accuracy imaging improves patient outcomes remains to be demonstrated in clinical trials. Methods: This multi-institutional phase III randomized clinical trial (PSMA-dRT, NCT04457245) was designed to randomize 312 men with unfavorable intermediate-risk or high-risk prostate cancer 1.08:1 between receiving (n=162) and not receiving (n=150) a PSMA PET/CT prior to starting dRT. Treating radiation oncologists incorporated the PSMA PET/CT into radiotherapy planning. All other imaging modalities were allowed in the control arm. There were no prespecified androgen deprivation therapy (ADT) or dRT dose and volumes protocols. The primary endpoint was 5-year progression-free survival (PFS). Results: 54 patients were randomized between November 2020 and December 2021 (25 to PSMA PET/CT and 29 to control). The trial closed early following FDA approval and insurance coverage of PSMA PET/CT, since treatment without PSMA PET/CT in the control group was no longer acceptable for many patients and physicians. Among patients staged with PSMA PET/CT in the intervention group, 14 patients (58.3%) had localized miT2b-cN0M0 disease, 6 (25.0%) had locally advanced disease (miT3a-bN0M0), 3 (12.5%) had regional disease (miN1M0), and 1 (4.2%) had nodal and distant disease (miN1M1b). Four patients (16.7%) were upstaged relative to their staging at time of randomization. All three patients with miN1M0 disease received pelvic lymph node irradiation as part of their dRT course. The patient with miN1M1b disease received upfront ADT with abiraterone acetate and prednisone followed by consolidative radiotherapy to the prostate and pelvic lymph nodes. With a median follow-up of 21 months (interquartile range: 17.6-26.3 months), there were no cases of biochemical failure (PSA >2 ng/mL above nadir), radiographic or biopsy-proven recurrence, salvage therapy, or prostate cancer death in either arm. Two-year PFS was 93.8% in the PSMA PET/CT arm (due to 2 non prostate cancer deaths) and 100% in the control arm. There was no significant difference in PFS between the PSMA PET/CT and control arms ( P=0.13). Conclusions: PSMA PET/CT upstaged 17% of patients compared to prior baseline staging, which allowed for more accurate treatment planning. Due to early termination, this trial was underpowered to assess the effect of PSMA PET/CT on PFS. PSMA-dRT is currently under submission for complete enrollment and data pooling at German sites. Clinical trial information: NCT04457245 .

Pretreatment colonoscopy impact on acute gastrointestinal (GI) toxicity following curative stereotactic body radiation therapy (SBRT) for localized prostate cancer.

Pretreatment colonoscopy impact on acute gastrointestinal (GI) toxicity following curative stereotactic body radiation therapy (SBRT) for localized prostate cancer.

A Phase 1 Trial of Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer After Brachytherapy

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter. Between August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment. The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.

PSMA PET imaging for evaluation of recurrent or persistent prostate cancer after primary prostate radiation.

35 Background: PSMA PET is increasingly utilized for the evaluation of disease stage at biochemical recurrence. Here we evaluate the association of clinico-pathologic features with PSMA findings in biochemically recurrent patients after primary prostate radiation therapy (RT). Methods: We queried the Northwestern Medical System Electronic Data Warehouse between July 2021 and March 2023 to identify 122 men treated with primary RT for presumptive localized prostate cancer who subsequently underwent Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT for staging. Patient characteristics, including demographic, clinical, pathological, and imaging variables were obtained. PSMA positivity for suspicious nodal or metastatic disease was determined based on radiology interpretation, with equivocal or likely benign lesions considered as negative findings. Patients with incomplete clinical history (n=3) were excluded. Clinical variables were compared using a Wilcoxon rank-sum and Fisher’s exact tests. Regression analysis was performed to determine variables associated with PSMA positivity in biochemically recurrent patients. Statistical significance was determined if the p-value was less than 0.05. Results: Among the 119 men staged with PET PSMA after RT, median PSA was 3.18 (IQR 1.35, 5.55 ng/mL). 78% (93/119) were found to have suspicious PSMA positive disease. 39% had PSMA positivity in the prostate only (46/119), 6.7% had pelvic nodal disease (8/119), and 33% had extrapelvic disease (39/119). On univariable regression analysis, PSA at the time of PSMA was the only factor associated with PSMA positivity (OR 1.32 per 1 point increase, 95% CI 1.10, 1.67, p=0.01; Table). Higher PSAs at the time of scan were additionally associated with distant recurrence (73.3% of men with distant recurrence if scanned at PSA >10ng/mL versus 31.9% if scanned at PSA <4ng/mL p=0.029). 20% (9/46) of men with PSMA positivity within the prostate were biopsied identifying 78% (7/9) positivity, of which 67% (4/6) receiving treatment selected management with salvage treatments. Conclusions: Patients with prostate cancer initially treated with RT showed significant rates of PSMA positive disease even when scanned at low PSAs (including many below the nadir+2ng/mL definition). Evaluation at low PSAs favors the identification of localized disease only which can be cured by salvage therapy if confirmed by biopsy (i.e. prostatectomy, cryoablation, HIFU). [Table: see text]

Does use of apalutamide enhance outcomes in combination with radiotherapy in metastatic hormone-sensitive prostate cancer? A real-world experience from the UK.

73 Background: Management of metastatic prostate cancer has undergone a significant change over the past decade, with the introduction of several novel agents and repurposing of others. Latest update from STAMPEDE trials shown prostate radiotherapy (RT) improves OS, without detriment in QoL in metastatic home sensitive prostate cancer mHSPC along with Docetaxel in those with low volume metastatic disease. There is no published data on impact of radiotherapy to prostate on Apalutamide treated mHSPC patients. Here we report our real-world experience of Apalutamide in mHSPC with radiotherapy. Methods: Patients with mHSPC (N = 266) from 5 UK centres, were treated with Apalutamide (240 mg) and ADT along with radiotherapy to prostate as per treating clinician’s discretion. The primary endpoint was objective rate (ORR) as determined by patients achieving a PSA decline of ≥90% (PSA90) and ≥50% (PSA50) and secondary endpoints included biochemical progression free survival (bPFS) and safety. Results: The median age for the whole cohort was 73.4 years (interquartile range 52 - 91), A total of 11.6% had received prior radical treatment (prostatectomy or radiotherapy for localised disease) and 88.4% had de novo metastatic disease. Median baseline PSA was 47 ng/ml (range 0.4-17100). The proportion of patients PSA90 and PSA50 at 3, 6 and 12 months is shown in the Table. Median PSA nadir was 0.1 ng/ml(rage 0.01- 48.2) and median time to reach nadir was 6 months (range 3-24 months). 13.5% (35) patients were treated with radiotherapy (RT) after at least 3 months (range 3 -6 months) of starting apalutamide. Patients received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) of radiotherapy (68 % vs 32%). Higher number of patients in RT group had achieved PSA90 compared to no radiotherapy cohort (97.14 % vs 87.3%, p =0.15). Patients treated with RT had median post treatment of PSA 0.01 ng/ml compared to 0.1 ng/ml in non RT group (p=0.0062). After median follow up of 8.4 months, proportion of patients shown biochemical progression in RT vs non RT group were 5.7 % vs 15 % respectively (p= 0.04). Patients with de novo metastatic disease have shown poor PSA response and higher chance of progression compared to patients who had initial radical treatment. Radiotherapy was well tolerated, with 17 % adverse events (Radiation Therapy Oncology Group grade 3–4) reported in radiotherapy group. Conclusions: Early experience of using apalutamide and radiotherapy in mHSPC showed improved PSA response and delayed progression. Treatment was well tolerated. Further follow up and clinical trials are needed to understand the impact on overall survival. [Table: see text]

Relugolix versus leuprolide in combination with radiotherapy for localized prostate cancer (REVELUTION trial): An initial analysis of patient treatment preferences and quality of life.

301 Background: Relugolix, an oral gonadotropin releasing hormone (GnRH) antagonist, has superior testosterone suppression and may lower cardiovascular (CV) toxicity compared with more commonly used injectable GnRH agonists, such as leuprolide. The Relugolix Versus Leuprolide Trial (REVELUTION, NCT 05320406) is an ongoing, investigator-initiated, randomized trial comparing radiotherapy (XRT) plus relugolix versus XRT plus leuprolide for men with localized prostate cancer (PCa). Primary endpoint is change in coronary plaque on cardiac computed tomography from baseline to 12 months following treatment. Secondary endpoints include patient-reported outcomes (PRO). Herein, we report patient-specific treatment preferences prior to randomization and acute treatment-associated toxicity. Methods: Men with non-metastatic intact or biochemically recurrent PCa pursuing pelvic XRT (1.8-2.5 Gy per fraction) with ≥ 6 months of androgen deprivation therapy (ADT) were enrolled and randomized 1:1 to leuprolide (IM/SC 45 mg q6mo) or relugolix (PO 360 mg day 1, 120 mg daily thereafter). Prior to randomization, each patient completed an ADT preference questionnaire after reviewing an education brochure describing both drugs’ administration, testosterone kinetics, and common toxicities. PROs were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC-CP) at baseline and 3-/6-months after XRT initiation, with higher scores indicating more severe toxicity. Scores were compared using linear mixed-effects models accounting for within-subject correlations. Results: Between 06/2022 and 07/2023, 65 men were randomized (34 leuprolide, 31 relugolix). Median follow-up was 5 months (IQR 4-8). Prior to randomization, 61 (94%) preferred relugolix over leuprolide, due to faster testosterone recovery (n=36, 59%), lower CV risk (n=23, 38%), or oral administration (n=2, 3%); the four patients who preferred leuprolide all had compliance concerns with a daily oral pill. Compared with XRT+leuprolide, XRT+relugolix was associated with less impact on IPSS urinary score (mean difference [MD] -3.68, p=0.04). There was no difference in EPIC-CP incontinence (MD +0.07, p=0.91), bowel (MD +0.39, p=0.44), sexual (MD -0.74, p=0.43), or vitality (MD +0.17, p=0.80). Conclusions: In this trial of men with localized PCa treated with XRT plus ADT, most preferred relugolix over leuprolide. Relugolix, compared with leuprolide, mitigated acute urinary toxicity from XRT, perhaps due to superior castration resulting in greater prostate gland downsizing and less obstructive uropathy. Longer-term follow up is ongoing, and primary CV toxicity endpoint is expected to be complete in 2024. Clinical trial information: NCT05320406 .

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

Prostate cancer and elective nodal radiation therapy for cN0 and pN0-anever ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Rectal ulceration and rectourethral fistula as rare complications of radiotherapy for prostate cancer—a case report and literature review

Rectal ulceration and rectourethral fistula as rare complications of radiotherapy for prostate cancer—a case report and literature review

Towards optimal heterogeneous prostate radiotherapy dose prescriptions based on patient-specific or population-based biological features.

Escalation of prescribed dose in prostate cancer (PCa) radiotherapy enables improvement in tumor control at the expense of increased toxicity. Opportunities for reduction of treatment toxicity may emerge if more efficient dose escalation can be achieved by redistributing the prescribed dose distribution according to the known heterogeneous, spatially-varying characteristics of the disease. To examine the potential benefits, limitations and characteristics of heterogeneous boost dose redistribution in PCa radiotherapy based on patient-specific and population-based spatial maps of tumor biological features. High-resolution prostate histology images, from a cohort of 63 patients, annotated with tumor location and grade, provided patient-specific "maps" and a population-based "atlas" of cell density and tumor probability. Dose prescriptions were derived for each patient based on a heterogeneous redistribution of the boost dose to the intraprostatic lesions, with the prescription maximizing patient tumor control probability (TCP). The impact on TCP was assessed under scenarios where the distribution of population-based biological data was ignored, partially included, or fully included in prescription generation. Heterogeneous dose prescriptions were generated for three combinations of maps and atlas, and for conventional fractionation (CF), extreme hypo-fractionation (EH), moderate hypo-fractionation (MH), and whole Pelvic RT+SBRT Boost (WPRT+SBRT). The predicted efficacy of the heterogeneous prescriptions was compared with equivalent homogeneous dose prescriptions. TCPs for heterogeneous dose prescriptions were generally higher than those for homogeneous dose prescriptions. TCP escalation by heterogeneous dose prescription was the largest for CF. When only using population-based atlas data, the generated heterogeneous dose prescriptions of 55 to 58 patients (out of 63) had a higher TCP than for the corresponding homogeneous dose prescriptions. The TCPs of the heterogeneous dose prescriptions generated with the population-based atlas and tumor probability maps did not differ significantly from those using patient-specific biological information. The generated heterogeneous dose prescriptions achieved significantly higher TCP than homogeneous dose prescriptions in the posterior section of the prostate. Heterogeneous dose prescriptions generated via biologically-optimized dose redistribution can produce higher TCP than the homogeneous dose prescriptions for the majority of the patients in the studied cohort. For scenarios where patient-specific biological information was unavailable or partially available, the generated heterogeneous dose prescriptions can still achieve TCP improvement relative to homogeneous dose prescriptions.

The impact of transportation mode, socioeconomic deprivation and rurality on travel times to radiotherapy and surgical services for patients with prostate cancer: A national population-based evaluation

BackgroundThe distances that patients have to travel can influence their access to cancer treatment. We investigated the determinants of travel time, separately for journeys by car and public transport, to centres providing radical surgery or radiotherapy for prostate cancer. MethodsUsing national cancer registry records linked to administrative hospital data, we identified patients who had radical surgery or radiotherapy for prostate cancer between January 2017 and December 2018 in the English National Health Service. Estimated travel times from the patients’ residential area to the nearest specialist surgical or radiotherapy centre were estimated for journeys by car and by public transport. ResultsWe included 13,186 men who had surgery and 26,581 who had radiotherapy. Estimated travel times by public transport (74.4 mins for surgery and 69.4 mins for radiotherapy) were more than twice as long as by car (33.4 mins and 29.1mins, respectively). Patients living in more socially deprived neighbourhoods in rural areas had the longest travel times to the nearest cancer treatment centres by car (62.0 mins for surgery and 52.1 mins for radiotherapy). Conversely patients living in more affluent neighbourhoods in urban conurbations had the shortest (18.7 mins for surgery and 17.9 mins for radiotherapy). ConclusionTravel times to cancer centres vary widely according to mode of transport, socioeconomic deprivation, and rurality. Policies changing the geographical configuration of cancer services should consider the impact on the expected travel times both by car and by public transport to avoid enhancing existing inequalities in access to treatment and patient outcomes.

Radiothérapie stéréotaxique du cancer de la prostate localisé : modalités, indications et rôle de l’urologue

Introduction: The aim was to report the modalities/indications of stereotactic body radiotherapy (SBRT) in localized prostate cancer (PCa) and to explain the role of the urologist in preparing for irradiation.Methods: A PubMed database search and narrative review of articles was performed in December 2023 to provide a comprehensive review of the literature on the subject. Only articles in French or English were examined.Results: SBRT generally delivers 35-40 Gy over 5 sessions, image-guided and intensity-modulated. In the primary treatment of localized CaP, SBRT is indicated in patients at low or favorable intermediate risk, without combination with androgen deprivation therapy, in selected patients and in expert centers, based on efficacy data from the HYPO-RT-PC trial, and safety data from the PACE-B trial. Stereotactic (re)irradiation would appear to provide similar oncological results to other treatment modalities, in the case of salvage treatment after primary non-surgical treatment. The results of the GETUG-31 trial are encouraging, but larger comparative studies are still needed to clarify the place of SBRT in this indication. The role of the urologist is paramount prior to SBRT, and a description of the preparation consisting in the placement of gold markers and Spacer is proposed (https://www.urofrance.org/formation/pose-de-fiduciaires-et-spacer-par-voie-transperineale/)Conclusion: SBRT in localized CaP is a therapy with growing indications, where urologist-radiotherapist collaboration is crucial.

Ultra-hypofractionated prostate cancer radiotherapy: Dosimetric impact of real-time intrafraction prostate motion and daily anatomical changes

PurposeTo retrospectively assess the differences between planned and delivered dose during ultra-hypofractionated (UHF) prostate cancer treatments, by evaluating the dosimetric impact of daily anatomical variations alone, and in combination with prostate intrafraction motion. MethodsProstate intrafraction motion was recorded with a transperineal ultrasound probe in 15 patients treated by UHF radiotherapy (36.25 Gy/5 fractions). The dosimetric objective was to cover 99 % of the clinical target volume with the 100 % prescription isodose line. After treatment, planning CT (pCT) images were deformably registered onto daily Cone Beam CT to generate pseudo-CT for dose accumulation (accumulated CT, aCT). The interplay effect was accounted by synchronizing prostatic shifts and beam geometry. Finally, the shifted dose maps were accumulated (moved-accumulated CT, maCT). ResultsNo significant change in daily CTV volumes was observed. Conversely, CTV V100% was 98.2 ± 0.8 % and 94.7 ± 2.6 % on aCT and maCT, respectively, compared with 99.5 ± 0.2 % on pCT (p < 0.0001). Bladder volume was smaller than planned in 76 % of fractions and D5cc was 33.8 ± 3.2 Gy and 34.4 ± 3.4 Gy on aCT (p = 0.02) and maCT (p = 0.01) compared with the pCT (36.0 ± 1.1 Gy). The rectum was smaller than planned in 50.3 % of fractions, but the dosimetric differences were not statistically significant, except for D1cc, found smaller on the maCT (33.2 ± 3.2 Gy, p = 0.02) compared with the pCT (35.3 ± 0.7 Gy). ConclusionsAnatomical variations and prostate movements had more important dosimetric impact than anatomical variations alone, although, in some cases, the two phenomena compensated. Therefore, an efficient IGRT protocol is required for treatment implementation to reduce setup errors and control intrafraction motion.

Impact of prostate position-based image-guidance in intensity-modulated radiation therapy for localized prostate cancer.

The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74Gy in 37 fractions). A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1years for the P-IGRT cohort and 10.8years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding.

Worsening of 2-year patient-reported intestinal functionality after radiotherapy for prostate cancer including pelvic node irradiation

Background and PurposeTo quantify patient-reported 2-year intestinal toxicity (IT) from pelvic nodal irradiation (PNI) for prostate cancer. The association between baseline/acute symptoms and 2-year worsening was investigated. Materials and MethodsPatient-reported IT was prospectively assessed through the Inflammatory Bowel Disease Questionnaire (IBDQ), filled in at baseline, radiotherapy mid-point and end, at 3 and 6 months and every 6 months until 5 years. Two-year deterioration of IBDQ scores relative to the Bowel Domain was investigated for 400 patients with no severe baseline symptoms and with questionnaires available at baseline, 2 years, RT mid-point and/or end and at least three follow-ups between 3 and 18 months. The significance of the 2-year differences from baseline was tested. The association between baseline values and ΔAcute (the worst decline between baseline and RT mid-point/end) was investigated. ResultsIn the IBDQ lower scores indicate worse symptoms. A significant (p < 0.0001) 2-year mean worsening, mostly in the range of −0.2/-0.4 points on a 1–7 scale, emerged excepting one question (IBDQ29, “nausea/feeling sick”). This decline was independent of treatment intent while baseline values were associated with 2-year absolute scores. The ΔAcute largely modulated 2-year worsening: patients with ΔAcute greater than the first quartile (Q1) and ΔAcute less or equal than Q1 showed no/minimal and highly significant (p < 0.0001) deterioration, respectively. Rectal incontinence, urgency, frequency and abdominal pain showed the largest mean changes (-0.5/-1): risk of severe worsening (deemed to be of clinical significance if ≤ 2) was 3–5 fold higher in the ΔAcute ≤ Q1 vs ΔAcute > Q1 group (p < 0.0001). ConclusionA modest but significant deterioration of two-year patient-reported intestinal symptoms from PNI compared to baseline was found. Patients experiencing more severe acute symptoms are at higher risk of symptom persistence at 2 years, with a much larger prevalence of clinically significant symptoms.

Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: Apropensity score-matched analysis.

Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. We compared 6‑year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, arotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. The median follow-up duration was 79months (> 6years). PSM generated amatched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6‑year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6and 68.8% of the patients achieved ≤ 1pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and avery low rate (4.4%) of grade ≥ 2 gastrointestinal complications. On the basis of PSM after a6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Implementation Readiness and Initial Effects of a Brief Mindfulness Audio Intervention Compared With a Brief Music Control During Daily Radiation Therapy for Prostate Cancer: A Randomized Pilot Study.

The most common and debilitating side effects of radiation therapy (RT) for prostate cancer (PC) are fatigue, sleep disturbance, anxiety, and depression. Previous research has reported palliative benefits from certain self-management approaches, such as mindfulness meditation. To develop, pre-test, and evaluate the feasibility, acceptability and initial benefit of brief, audio-based mindfulness delivered during daily RT for PC compared to a relaxing music control. Following intervention development, participants were randomized to either brief guided mindfulness audio recordings or a relaxing music control during daily RT. A pre-testing phase was first conducted to determine optimal program start time, length, and content most associated with retention. A final program (n = 26) was delivered daily, starting on day one of week 2 of RT and lasting 4 consecutive weeks. Feasibility was defined as ≥70% on enrollment rate, retention, and audio program adherence. Acceptability was measured with a 12-item post-study survey. A secondary focus compared between group changes on patient reported outcomes of fatigue, anxiety, depression, sleep disturbance, and related outcomes at baseline and follow up assessments. Descriptive statistics and general linear models were used. Overall, 76% (n = 38) of approached men enrolled. Pre-testing retention rates were <70% while the final program's retention rate was 89%. The majority of acceptability criteria were met in both conditions, with relatively higher ratings in the mindfulness arm. Compared to music controls, mindfulness participants demonstrated significantly less uncertainty intolerance at 4-weeks (P = .046, d = .95); and significantly lower fatigue scores (P = .049, d = 1.3) and lower sleep disturbance scores (P = .035, d = 1.1) at the 3months follow up. The final intervention met feasibility and acceptability criteria. Pre-testing refinements played a key role for optimal program delivery and retention. Audio-based mindfulness delivered during RT for PC hold potential to help decrease RT-related physical and emotional side effects.

Impact of daily plan adaptation on accumulated doses in ultra-hypofractionated magnetic resonance-guided radiation therapy of prostate cancer

Background and purposeUltra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose. Materials and methodsTwenty-three prostate cancer patients treated at two clinics with 0.35 T magnetic resonance-guided linear accelerator (MR-linac) following the same treatment protocol (5×7.5 Gy with urethral sparing and daily adaptation) were included. The fraction MR images were deformably registered to the planning MR image. Both non-adapted and adapted fraction doses were accumulated with the corresponding vector fields. Two DIR approaches were implemented. PTV* (planning target volume minus urethra+2mm) D95%, CTV* (clinical target volume minus urethra) D98%, and OARs (urethra+2mm, bladder, and rectum) D0.2cc, were evaluated. Statistical significance was inferred from a two-tailed Wilcoxon signed-rank test (p < 0.05). ResultsNormalized to the baseline, the accumulated PTV* D95% increased significantly by 2.7 % ([1.5, 4.3]%) through adaptation, and the CTV* D98% by 1.2 % ([0.1, 1.7]%). For the OARs after adaptation, accumulated bladder D0.2cc decreased by 0.4 % ([−1.2, 0.4]%), urethra+2mmD0.2cc by 0.8 % ([−1.6, −0.1]%), while rectum D0.2cc increased by 2.6 % ([1.2, 4.9]%). For all patients, rectum D0.2cc was still below the clinical constraint. Results of both DIR approaches differed on average by less than 0.2 %. ConclusionsOnline adaptation in MRgRT improved target coverage and OARs sparing at the level of accumulated dose.

Longitudinal analysis of T2 relaxation time variations following radiotherapy for prostate cancer

Aim of this paper is to evaluate short and long-term changes in T2 relaxation times after radiotherapy in patients with low and intermediate risk localized prostate cancer. A total of 24 patients were selected for this retrospective study. Each participant underwent 1.5T magnetic resonance imaging on seven separate occasions: initially after the implantation of gold fiducials, the required step for Cyberknife therapy guidance, followed by MRI scans two weeks post-therapy and monthly thereafter. As part of each MRI scan, the prostate region was manually delineated, and the T2 relaxation times were calculated for quantitative analysis. The T2 relaxation times between individual follow-ups were analyzed using Repeated Measures Analysis of Variance that revealed a significant difference across all measurements (F (6, 120) = 0.611, p << 0.001). A Bonferroni post hoc test revealed significant differences in median T2 values between the baseline and subsequent measurements, particularly between pre-therapy (M0) and two weeks post-therapy (M1), as well as during the monthly interval checks (M2 - M6). Some cases showed a delayed decrease in relaxation times, indicating the prolonged effects of therapy. The changes in T2 values during the course of radiotherapy can help in monitoring radiotherapy response in unconfirmed patients, quantifying the scarring process, and recognizing the therapy failure.

Patient-reported Side Effects 1 Year After Radical Prostatectomy or Radiotherapy for Prostate Cancer: A Register-based Nationwide Study

BackgroundData on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts. ObjectiveTo assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot-assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient-reported outcome measures in the Swedish prostate cancer database.Design, setting, and participants: This was a nationwide, population-based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020.Outcome measurements and statistical analysis: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics. Resultsand limitations: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 5% after RT. The frequency of urinary bother was similar, at 18% after RARP and 17% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 80% of men had ED after RARP, and 82% after RT. High QoL was reported by 85% of men after RARP and 79% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.24, 95% confidence interval [CI] 0.19–0.32), urinary bother (OR 0.74, 95% CI 0.61–0.89), and ED (OR 0.57, 95% CI 0.48–0.67), but higher risk of bowel symptoms (OR 2.84, 95% CI 2.40–3.37). QoL was higher after RARP than after RT (OR 1.33, 95% CI 1.11–1.60). ConclusionsShort-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP. Patient summaryIn our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects.