| 1. |
- Anand, Aseem, et al.
(författare)
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Assessing Radiographic Response to 223Ra with an Automated Bone Scan Index in Metastatic Castration-Resistant Prostate Cancer Patients
- 2020
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X .- 1535-5667. ; 61:5, s. 671-675
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Tidskriftsartikel (refereegranskat)abstract
- For effective clinical management of patients being treated with 223Ra, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate an automated bone scan index (aBSI) as a quantitative assessment of bone scans for radiographic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In a multicenter retrospective study, bone scans from patients with mCRPC treated with monthly injections of 223Ra were collected from 7 hospitals in Sweden. Patients with available bone scans before treatment with 223Ra and at treatment discontinuation were eligible for the study. The aBSI was generated at baseline and at treatment discontinuation. The Spearman rank correlation was used to correlate aBSI with the baseline covariates: alkaline phosphatase (ALP) and prostate-specific antigen (PSA). The Cox proportional-hazards model and Kaplan-Meier curve were used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). The concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS. Results: Bone scan images at baseline were available from 156 patients, and 67 patients had both a baseline and a treatment discontinuation bone scan (median, 5 doses; interquartile range, 3-6 doses). Baseline aBSI (median, 4.5; interquartile range, 2.4-6.5) was moderately correlated with ALP (r = 0.60, P < 0.0001) and with PSA (r = 0.38, P = 0.003). Among baseline covariates, aBSI (P = 0.01) and ALP (P = 0.001) were significantly associated with OS, whereas PSA values were not (P = 0.059). After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) of patients demonstrated a decline in aBSI, ALP, and PSA, respectively. As a continuous variable, the relative change in aBSI after treatment, compared with baseline, was significantly associated with OS (P < 0.0001), with a C-index of 0.67. Median OS in patients with both aBSI and ALP decline (median, 134 wk) was significantly longer than in patients with ALP decline only (median, 77 wk; P = 0.029). Conclusion: Both aBSI at baseline and its change at treatment discontinuation were significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with 223Ra.
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| 2. |
- Bernhardt, Peter, 1966, et al.
(författare)
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Dosimetric analysis of the short-ranged particle emitter161 tb for radionuclide therapy of metastatic prostate cancer
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq ) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 3. |
- Braide, Karin, et al.
(författare)
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A comparison of side-effects and quality-of-life in patients operated on for prostate cancer with and without salvage radiation therapy
- 2020
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 54:5, s. 393-400
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:The extent of late side-effects in prostate cancer patients, after radical prostatectomy (RP = reference group) and salvage radiation therapy (SRT) in a self-reporting perspective (PROM) is still under-reported. We aimed to investigate the rate and severity of side-effects and quality-of-life (QoL) according to PROM. Methods and materials:A PROM survey was administered to a cohort of SRT patients matched to a reference group with median follow-up 10 years after surgery. In total, 740 patients were analyzed. To investigate the association between SRT versus reference group regarding side-effects and QoL, a Poisson regression analysis was conducted and presented as relative risk estimates (RR) together with 95% confidence intervals regarding questions related to urinary, rectal, sexual symptoms and QoL. Results:RRs ranged from of 1.7-6.5 on rectal symptoms and 1.2-1.4 for urinary symptoms. In general health, QoL and sexual function all RRs were below 1.1. With increasing age, higher RRs were seen for urinary leakage and lowered sexual function whereas longer time following irradiation showed higher RRs for rectal symptoms and rectal leakage. Limitations of this study include the cross-sectional design and lack of baseline assessment. Conclusions:Adding SRT to RP does not seem to result in other than acceptable side-effects in the majority of men receiving SRT when taking a long follow-up time (median 10 years after surgery) into account. However, a subset of men develop severe side-effects where rectal bleeding dominates.
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| 4. |
- Braide, Karin, et al.
(författare)
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Risk of severe late toxicity after radiotherapy following radical prostatectomy - a nationwide study
- 2022
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Ingår i: Bju International. - : Wiley. - 1464-4096 .- 1464-410X. ; 130:6, s. 799-808
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Tidskriftsartikel (refereegranskat)abstract
- Objective To estimate the long-term risks of severe late toxicities for radiation therapy (RT) following radical prostatectomy (RP) in an unselected nationwide cohort, as severe side-effects are rare but may occur years later. Patients and Methods The study population comprised all men undergoing RP between 1997 and 2016 in the Prostate Cancer database Sweden (PCBaSe) (n = 40 962). By (1:2) matching, two cohorts were created: 2789 men exposed to postoperative RT and 5578 unexposed men with comparable age, comorbidities, and year of surgery. Cumulative incidences and rate ratios were calculated for the following outcomes: symptoms and interventions of the urinary or intestinal tract demanding inpatient care, secondary malignancies, and non-prostate cancer mortality. Results The largest differences were seen for late toxicities affecting the urinary tract. The 10-year cumulative incidences among those exposed to postoperative RT vs the RP-only group were: 17.8% vs 10.5% for procedures of the urinary tract (difference 7.3%, 95% confidence interval [CI] 4.4 to 10.3; relative risk [RR] 1.74, 95% CI 1.47 to 2.05); 6.0% vs 1.2% for haematuria (difference 4.8%, 95% CI 3.1 to 6.5; RR 6.50, 95% CI 4.31 to 10.10); and 2.4% vs 1.1% for bladder cancer (difference 1.4%, 95% CI 0.4 to 2.3; RR 2.71, 95% CI 1.72 to 4.33). The groups were similar regarding intestinal toxicity, other secondary malignancies, and non-prostate cancer mortality. Adjustments for preoperative tumour risk factors did not importantly affect the rate ratios. Conclusion Severe late toxicity after postoperative RT following RP predominately affects the bladder and can appear many years after RT.
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| 5. |
- Braide, Karin, et al.
(författare)
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Salvage radiation therapy in prostate cancer: relationship between rectal dose and long-term, self-reported rectal bleeding
- 2021
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Ingår i: Clinical & Translational Oncology. - : Springer Science and Business Media LLC. - 1699-048X .- 1699-3055. ; 23:2, s. 397-404
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To quantify the relationship between the rectal dose distribution and the prevalence of self-reported rectal bleeding among men treated with salvage radiotherapy (ST) delivered by three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. To use this relationship to estimate the risk of rectal bleeding for a contemporary cohort of patients treated with volumetric modulated arc therapy (VMAT) ST. Methods and patients Rectal bleeding of any grade was reported by 56 (22%) of 255 men in a PROM-survey at a median follow-up of 6.7 years after 3DCRT ST. Treatment plan data were extracted and dose-response relationships for the rectal volumes receiving at least 35 Gy (V-35Gy) or 63 Gy (V-63Gy) were calculated with logistic regression. These relationships were used to estimate the risk of rectal bleeding for a cohort of 253 patients treated with VMAT ST. Results In the dose-response analysis of patients in the 3DCRT ST cohort, both rectal V(35Gy)and V(63Gy)were statistically significant parameters in univariable analysis (p = 0.005 and 0.003, respectively). For the dose-response models using either rectal V(35Gy)or V-63Gy, the average calculated risk of rectal bleeding was 14% among men treated with VMAT ST compared to a reported prevalence of 22% for men treated with 3DCRT ST. Conclusions We identified dose-response relationships between the rectal dose distribution and the risk of self-reported rectal bleeding of any grade in a long-term perspective for men treated with 3DCRT ST. Furthermore, VMAT ST may have the potential to decrease the prevalence of late rectal bleeding.
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| 6. |
- Braide, Karin, et al.
(författare)
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The value of a bladder-filling protocol for patients with prostate cancer who receive post-operative radiation: results from a prospective clinical trial
- 2019
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 58:4, s. 463-468
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: This study compares two different strategies for maintaining a constant bladder volume during a course of postoperative radiotherapy in prostate cancer. In addition, we studied how changes in bladder filling affect the clinical target volume (CTV) and the coverage hereof. Material and Methods: Twenty-nine patients with PSA-relapse after radical prostatectomy were divided into two groups: voiding and drinking 300 ml 1 hour before treatment (Group 1); and maintained a comfortably filled bladder (Group 2). The bladder volumes were calculated based on the planning CT (pCT) and a weekly Cone Beam CT (CBCT) during the treatment period. Furthermore, the variability of bladder extension was analyzed and correlated to the volume of the bladder covered with the 95% of the dose (V-95%,V-bladder). Results: The estimated median bladder volumes were 120 ml (95% CI: (93, 154)) and 123 ml (95% CI: (98, 155)) in groups 1 and 2, respectively. The intra-individual variation in bladder volume, assessed as the standard deviation, was 64 ml (95% CI: (46, 105)) in Group 1 and 61 (95% CI: (45, 94)) ml in Group 2. Increasing the bladder volume extended the bladder cranially while the caudal extension was almost constant. The correlation between bladder volume and V-95%,V-bladder was 3.5 ml per 100 ml in group 1 and 1.2 ml per 100 ml in group 2 with no significant difference. Conclusions: The intention to maintain a constant volume for the bladder is not fulfilled with either of the protocols in this study, and changes in bladder volumes does not seem to affect the position, or the coverage of the CTV.
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| 7. |
- Corsini, Christian, et al.
(författare)
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Patient-reported side effects 1 year after radical prostatectomy or radiotherapy for prostate cancer : a register-based nationwide study
- 2024
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts.OBJECTIVE: To 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.RESULTS AND 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 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19-0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61).CONCLUSIONS: Short-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 SUMMARY: In 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.
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| 8. |
- Corsini, Christian, et al.
(författare)
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Patient-reported Side Effects 1 Year After Radical Prostatectomy or Radiotherapy for Prostate Cancer : A Register-based Nationwide Study
- 2024
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, populationbased cohorts. Objective: To 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. Results and 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 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19- 0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61). Conclusions: Short-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 summary: In 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. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 9. |
- Dillner, Karin, 1974, et al.
(författare)
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Gene expression analysis of prostate hyperplasia in mice overexpressing the prolactin gene specifically in the prostate.
- 2003
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 144:11, s. 4955-66
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Tidskriftsartikel (refereegranskat)abstract
- The probasin (Pb)-PRL transgenic mice that overexpress the rat PRL gene specifically in the prostate develop a dramatic enlargement of the prostate gland. The objective of this study was to characterize the molecular mechanisms involved in the prostate hyperplasia seen in the Pb-PRL transgenic mice. cDNA microarray analysis was used to identify differentially expressed transcripts in the hyperplastic prostates of 6-month-old transgenic mice compared with age-matched controls. We report the identification of 266 genes (175 up-regulated and 91 down-regulated) that were differentially expressed in the enlarged transgenic prostates compared with controls. Subsequential real-time RT-PCR was used to verify a set of differentially regulated transcripts. The hyperplastic prostates of Pb-PRL transgenic mice demonstrate a molecular pattern supporting the importance of reduced degree of apoptosis for the development of the phenotype. Immunohistochemical analysis of apoptotic activity using two different markers of apoptosis (single-stranded DNA and activated caspase-3) were performed, and the results showed diminished apoptosis activity in the prostate of Pb-PRL transgenic mice compared with control prostates. The increased stromal/epithelial ratio of the Pb-PRL transgenic prostate together with up-regulation of a significant fraction of genes involved in tissue remodeling activity, including the synthesis and degradation of the extracellular matrix and changes in protease activity, suggest that activation of the stroma is involved in the development of prostate hyperplasia. Overall, the differentially expressed transcripts identified in this study show many molecular similarities between the prostate hyperplasia of PRL-transgenic mice and human prostate pathology, including both benign prostatic hyperplasia and prostate cancer.
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| 10. |
- Fransson, Per, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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