BACKGROUND:HYPO-RT-PC is a phase 3 trial comparing ultra-hypofractionated and conventionally fractionated radiotherapy in intermediate-to-high-risk localised prostate cancer. This 10-year update reports long-term efficacy and toxicity outcomes. METHODS:In this open-label, randomised, phase 3, non-inferiority trial done in ten centres in Sweden and two in Denmark, we recruited men aged 75 years or younger with intermediate-risk or high-risk prostate cancer and a WHO performance status between 0 and 2. Previous or current androgen deprivation therapy was not permitted. Patients were randomly assigned (1:1) to ultra-hypofractionated radiotherapy (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventionally fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). Randomisation was performed with a minimisation algorithm balancing T stage, Gleason score, prostate-specific antigen, and trial centre. The primary endpoint was failure-free survival, defined as time from randomisation to the first occurrence of biochemical failure, evidence of clinical progression, initiation of androgen deprivation therapy, or death from prostate cancer, analysed in the per-protocol population. The non-inferiority margin was 4% at 5 years and had previously been met, corresponding to a critical hazard ratio (HR) limit of 1·338. Toxicity was assessed using the Radiation Therapy Oncology Group morbidity scale. Here, we report long-term efficacy and safety results at 10 years. The trial is registered with the ISRCTN registry, ISRCTN45905321, and is closed. FINDINGS:Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionated radiotherapy (n=602) or ultra-hypofractionated radiotherapy (n=598). Ten patients withdrew consent, eight were found to be ineligible, and two died of reasons unrelated to prostate cancer. 1180 patients constituted the per-protocol population (591 in the conventional fractionation group and 589 in the ultra-hypofractionation group). After a median follow-up of 10·6 years (IQR 9·0-13·0) in the conventional fractionation group and 10·7 years (9·1-12·7) in the ultra-hypofractionation group, 205 and 178 primary events were observed, respectively. 10-year failure-free survival was 65% (95% CI 61-69) in the conventionally fractionated group and 72% (68-76) in the ultra-hypofractionated group. The adjusted HR for the primary endpoint was 0·84 (95% CI 0·69-1·03; Cox regression analysis), confirming non-inferiority. The 10-year cumulative incidence of late grade 2 or worse genitourinary toxic effects was 30% (95% CI 26-34) in the conventional fractionation group and 28% (24-32) in the ultra-hypofractionated group (HR 1·01, 95% CI 0·81-1·25; p=0·95). For late grade 2 or worse gastrointestinal toxic effects, the corresponding figures were 14% (95% CI 11-18) and 14% (11-17; HR 0·94, 95% CI 0·70-1·28; p=0·72). INTERPRETATION:This 10-year follow-up confirms the non-inferiority of the ultra-hypofractionated radiotherapy regimen compared with the conventionally fractionated, with similar toxicity profiles. The findings support the seven-fraction schedule as a safe, effective, and practical standard-of-care option for patients with intermediate-risk prostate cancer. FUNDING:The Nordic Cancer Union, the Swedish Cancer Society, the Swedish Research Council, the Swedish Prostate Cancer Association, and Cancerforskningsfonden i Norrland.

Background:The radiosensitizing effect of epidermal growth factor inhibitors (EGFRIs), such as cetuximab, in patients with p16-positive HPV-associated oropharyngeal squamous cell carcinoma (HPV + OPSCC) is not clear. There is no randomized trial investigating the addition of EGFRI to radiotherapy (RT) alone specifically in HPV + OPSCC, and available evidence in subgroup analyses have mostly suggested discouraging results. The current analysis provides additional data by combining results from two randomized trials. Materials and Methods:Patients from two randomized ARTSCAN trials were included. The RT alone-group consisted of patients treated with conventionally fractionated RT (68.0 Gy in 34 fractions over 6.5 weeks) in the first ARTSCAN trial. The cetuximab group comprised patients treated with conventionally fractionated RT (same RT-schedule) and receiving concurrent cetuximab in the ARTSCAN III trial. Only patients with HPV + OPSCC were included. Comparisons between groups were made by univariable and adjusted Cox regression models, and illustrated with the Kaplan-Meier method. Results:74 and 89 patients were eligible in the first ARTSCAN trial (RT alone) and ARTSCAN III (RT + cetuximab), respectively, with a median follow-up of 5.3 (interquartile range 5.0-5.5) years. Baseline characteristics were generally well-balanced. The five-year loco-regional control for RT alone was 84% (95%CI 76-93) and for RT + cetuximab 82% (95%CI 75-91), with an adjusted hazard ratio of 1.18 (95%CI 0.54-2.6, p = 0.70). Interpretation:The study does not support a radiosensitizing role when adding EGFRI cetuximab to RT in patients with HPV + OPSCC.

BACKGROUND AND PURPOSE:The ARTSCAN 2 randomised controlled trial compares accelerated fractionation (AF) radiotherapy (RT) in a preoperative setting with conventional fractionation (CF) RT postoperatively for oral cavity cancer (OCC). Current results indicate no advantage for preoperative AF RT, thereby reinforcing postoperative CF RT as the "gold standard" of care. This analysis of the trial focuses on health-related quality of life (HRQoL) and conducts a health-economic evaluation from a societal perspective. MATERIALS AND METHODS:240 patients formed the intention-to-treat population. Preoperative AF RT was given twice daily during 4.5 weeks to a total dose of 68 Gy followed by surgery 4-6 weeks later. Postoperative CF RT was given to a total dose of 60 or 66 Gy during 6-7 weeks. In the per protocol population, HRQoL was assessed with the EORTC QLQ-C30, QLQ-H&N35, and HADS questionnaires at five occasions during the five-year follow-up period. Direct and indirect costs were retrieved, and a cost-utility analysis (CUA) was conducted using quality-adjusted life years (QALYs) as outcome measure. RESULTS:HRQoL was analysed in 218 patients (i.e., the per-protocol population), of whom 204 were included in the CUA. Up until two years after treatment, the preoperative AF RT-group featured significantly worse HRQoL in a few of the QLQ-H&N35 scales compared to the postoperative CF RT-group. In the CUA, preoperative AF RT was less effective and more expensive than postoperative CF RT. CONCLUSION:Postoperative CF RT is associated with fewer symptoms in selected head-and-neck-specific domains and is more cost-effective than preoperative AF RT in the treatment of OCC.

PURPOSE Organ preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response. METHODS Data from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with ≤10% cancer cells—nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM. RESULTS Five hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8% v 10.2%; P ≤ .001). Independent risk factors for DM included LR ( v TME at reassessment; P = .001), ypT3-4 status ( P = .016), and ypN+ status ( P = .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75% v 87%; P = .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages ( P ≤ .009). CONCLUSION Patients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes.

Importance The management of complications following oral cavity squamous cell carcinoma (OCSCC) surgery can be challenging. Previous studies show conflicting results on complication risks after preoperative radiotherapy (RT), necessitating a randomized controlled trial (RCT). Objective To compare early complications during hospitalization for OCSCC surgery between patients receiving preoperative accelerated fractionated RT and those planned for but not yet exposed to RT. Design A part of the ARTSCAN 2 RCT comparing preoperative accelerated RT with postoperative conventionally fractionated RT for OCSCC. Setting A multicentre trial in 6 tertiary care hospitals in Sweden. Participants Untreated and resectable OCSCC patients of all stages recommended combination treatment by the local multidisciplinary board. Intervention Preoperative accelerated RT was administered twice daily to a total dose of 68 Gy, completed 4 to 6 weeks before surgery. Main Outcome Measures Complications during hospitalization included wound infection, neck flap necrosis, chyle leakage, oro/pharyngocutaneous fistula, free flap necrosis, tracheostomy, revision surgery, and medical complications. Length of surgery, perioperative blood loss, and transfusions were also monitored. Results Two hundred and twenty-one patients were eligible for analysis: 103 in the preoperative RT group and 118 not yet exposed to RT. Complication rates were low, with no statistically significant differences between groups. Patients receiving preoperative RT had similar wound infection rates (12/103; 11.7%) to those not exposed (9/118; 7.6%) ( P = .31). Among free flap patients, 1/40 (2.5%) in the preoperative RT group and 3/52 (5.8%) in the unirradiated group had free flap necrosis ( P = .63). No differences were found in oro/pharyngocutaneous fistula frequency (3/103; 2.9% vs 3/118; 2.5%) ( P = 1.00). Conclusion and Relevance Preoperative accelerated RT at 68 Gy, administered 4 to 6 weeks before surgery, does not increase early complications. Although survival rates, morbidities, quality of life, and societal costs need consideration in the ARTSCAN 2 assessment, our findings show that early postoperative complication risks remain unchanged by preoperative RT. Trial Registration ISRCTN, ISRCTN00608410, Registered 20 March 2008—Retrospectively registered, https://www.isrctn.com/ISRCTN00608410 .

PURPOSE:The study investigated curative radiation therapy (RT) plus cisplatin versus RT plus cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS:This was a Swedish multicenter randomized phase 3 study. Included patients were randomized 1:1. Patients with T3-T4 tumors underwent a second randomization 1:1 between a final RT dose of 68.0 and 73.1 Gy to the primary tumor. Cisplatin dosage was 40 mg/m2/wk during RT. Cetuximab was administered with a loading dose of 400 mg/m2 1 week before start of RT, followed by weekly doses of 250 mg/m2 during RT. Primary endpoint was overall survival (OS), evaluated by adjusted Cox regression analysis. Secondary endpoints were locoregional control, pattern of failure, morbidity, quality of life (QL), and comparisons between dose-escalated RT and standard-dose RT in T3-T4 tumors. RESULTS:Following an unplanned interim analysis, patient inclusion was prematurely closed. The intention-to-treat population included 291 patients, 76% of whom had p16-positive oropharyngeal cancer. Median follow-up was 7.5 years for OS and 5.3 years for treatment efficacy. Five-year OS was 82% (95% confidence interval [CI], 76-89) in the RT plus cisplatin group compared with 71% (95% CI, 64-79) in the RT plus cetuximab group (log-rank P = .019). Adjusted hazard ratios for OS, locoregional failure, and distant failure were 1.66 (95% CI, 1.08-2.56; P = .021), 2.24 (95% CI, 1.25-4.02; P = .007), and 1.44 (95% CI, 0.67-3.09; P = .34), respectively, for patients treated with concomitant cetuximab versus cisplatin. Although potentially affected by the early termination of patient inclusion, no improvement in local control was found in patients with T3-T4 tumors receiving RT dose escalation (adjusted HR, 0.63; 95% CI, 0.30-1.34; P = .23). Late morbidity and QL were similar between the treatment groups. CONCLUSIONS:The study showed inferior treatment outcomes for cetuximab compared with cisplatin concurrent with RT. Cisplatin remains standard concomitant treatment for locoregionally advanced HNSCC.

BACKGROUND AND PURPOSE:HYPO-RT-PC was the first phase 3 trial showing the long-term efficacy and safety of extremely hypofractionated radiotherapy schedules (ultra-hypofractionation or stereotactic body radiotherapy) compared with standard radiotherapy in localised prostate cancer. We aimed to verify their safety in the context of a clinical trial, by comparing events of potentially radiotherapy-related morbidity according to routinely collected health data between the arms and with men unexposed to prostate radiotherapy. MATERIALS AND METHODS:We included Swedish residents in the per-protocol population and unexposed men matched with the ultra-hypofractionation group. Primary outcomes were genitourinary and gastrointestinal events defined by linking the Common Terminology Criteria for Adverse Events version 5.0 to diagnosis and intervention codes in broad (any related condition) and narrow code sets (strongly related conditions) tested separately. Inpatient care, interventions, and causes of death, identified in Swedish national healthcare registers, were events. Outcomes were analysed as time-to-event, adjusted for Charlson Comorbidity Index and socioeconomic status. RESULTS:Five hundred and forty-one participants (92%) from each trial arm and 2705 unexposed men were included. We found no statistically significant differences between the radiotherapy groups (broad code sets: genitourinary events, adjusted hazard ratio 0.95, 95% confidence interval 0.71-1.25; gastrointestinal events, 1.24, 0.91-1.69). Compared with the unexposed men, 10-year excess cumulative incidence was 8% and 5% for genitourinary and 5% and 4% for gastrointestinal events when applying the broad and narrow code sets, respectively, without excess mortality events. CONCLUSION:The results support the HYPO-RT-PC findings by showing similar morbidity between ultra-hypofractionated and standard radiotherapy. Excess events were estimated to 4-8%, without increased associated mortality.

BACKGROUND:The aim of this study was to compare relative survival in non-metastatic rectal cancer clinically staged as T3-T4 requiring beyond total mesorectal excision (TME) to that after standard TME. METHODS:This population-based study included all patients operated with anterior resection, abdominoperineal excision or Hartmann's procedure for non-metastatic rectal cancer clinically staged as T3-T4 in Sweden between 2009 and 2018. Relative survival was analysed in relation to surgery beyond TME (bTME), which was subcategorized as bTME- and bTME + to account for extent of resection. In all survival analyses, follow-up started at 90 days after surgery. Based on a causal model defined a priori excess mortality rate ratios (EMRR) were estimated using Poisson regression. RESULTS:Of 8272 included patients 1220 (14.7 %) were operated bTME. In a model adjusted for age and sex bTME was associated with higher excess mortality compared to standard TME (EMRR: 1.76, 95%CI:1.52-2.04). This association persisted after additional adjustment for tumour characteristics, neoadjuvant therapy and hospital volume (EMRR: 1.32, 95%CI:1.11-1.56) and was mainly attributable to restricted relative survival after bTME- (EMRR: 1.42, 95%CI:1.18-1.72) as EMRR after bTME+ was 1.07 (95%CI:0.80-1.44). CONCLUSION:This national population-based study showed inferior relative survival after bTME compared to standard TME in non-metastasized rectal cancer cT3-cT4. Unexpectedly this difference was mainly seen after bTME of limited extent.

Importance The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed. Objectives To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time. Design, Setting, and Participants This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023. Exposure Major surgery for cancer. Main Outcomes and Measures The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated. Results A total of 432 218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4 009 343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis. Conclusions and Relevance This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.

Abstract Introduction The ongoing PRORECT trial (NCT04525989) randomises between short-course radiotherapy (SCRT) using proton beam (PBT) or photon radiotherapy in total neoadjuvant therapy (TNT). Primary endpoint is preoperative toxicity. This report compares short-term surgical outcomes between the two arms. Method Patients with locally advanced rectal cancer with at least one risk criteria (cT4, cN2, EMVI+, MRF+ and/or lateral lymph nodes) on MRI were included. All patients received TNT (SCRT + 4 CAPOX). Post-operative complications were according to Clavien-Dindo, anastomotic leaks according to Rahbari and specimen quality according to Quirke. Result The first 10 consecutively operated patients in each arm were analysed. There was no 30-day postoperative mortality. Distribution of sex, age, and tumour stage and height was similar between groups. Median time from radiotherapy to surgery was 129 days in PBT and 142 days in photon treated. Seventeen operations were robot-assisted and 5 patients in each group had anterior resection and abdominoperineal excision (APE). Extended surgery was performed in 4 patients (PBT=3). Major complications (> CD3b) occurred in 3 patients (PBT=2), anastomotic leak in 3 (PBT=1) and perineal complications after APE in 3 (PBT=1). R0 resection was achieved in 18 patients, 9 in each group. Pathological complete response was detected in 3 patients (PBT=2) and ypT0 in 4 (PBT=3) (thus, 1 ypT0N1). Specimen quality was judged as the correct mesorectal plane in 17 (PBT=9). Discussion These preliminary results of the first 20 patients having undergone TNT and surgery in the PRORECT trial indicate that PBT has no negative impact on early surgical outcomes.

AIM:The standard treatment for anal cancer is chemoradiotherapy. Most patients survive anal cancer but remain living with long-term side effects related to the treatment received. The aim of this study was to assess the occurrence of long-term impairment of urinary and sexual function at 3 and 6 years after diagnosis and to investigate the additive effect from chemotherapy in combined chemoradiotherapy on urinary incontinence, compared to radiotherapy alone. METHOD:The ANal CAncer study (ANCA) is based on a national Swedish cohort of patients diagnosed with anal cancer between 2011 and 2013. All identified patients within the study were invited to respond to a study-specific questionnaire at 3 and 6 years. Descriptive analyses for the primary endpoint were performed. To investigate a possible additional effect from chemotherapy logistic regression was used. RESULTS:A total of 388 patients were included in the study. At 3 years 264 patients were alive and invited to respond to an anal cancer specific questionnaire. The 3- and 6 year response rates were 195 (74%) and 155 patients (67%), respectively. The patient reported urinary function impairment at 3 years were urgency (63%), incomplete bladder emptying (47%), and incontinence (46%) and there was an absolute increase of the prevalence of urinary dysfunction in about 10% at 6 years. Three years after diagnosis, 77% reported that intercourse was not part of their sex life; this percentage increased at 6 years to 83%. We found no negative effect of chemotherapy in combined chemoradiotherapy versus radiotherapy alone on patient reported urinary incontinence. CONCLUSION:For anal cancer survivors, urinary function was impaired after 3 years and continued to deteriorate as measured at 6 years after diagnosis. Anal cancer and its treatment negatively affected sexual function for both men and women. This may explain why patients reported that sexual activity and frequency of intercourse was not of importance in their life.

Background Colorectal cancer is common and prognosis is improving. The conditions of survivors of treatment, including financial consequences, are thus important. The aim of this study was to quantify loss of earnings and work loss in working-age patients with colon and rectal cancer relative to matched comparators. Methods The study utilised data from the CRCBaSe database that is generated from the nationwide Swedish ColoRectal Cancer Register and includes data from several Swedish nationwide registers. The study period was 1995-2020 for rectal cancer patients and 2007-2020 for colon cancer patients. A retrospective population-based nationwide cohort study on earnings, disposable income, and work loss, in survivors of stage I-III colorectal cancer treatment was undertaken. Median regression was used to analyse earnings and disposable income, and logistic regression to analyse the probability of work loss. Findings A cohort of 8863 colorectal cancer survivors diagnosed before 2017 and 52,514 comparators matched on birth year, legal sex, and county of residence, was analysed. There was a clear reduction in earnings between the calendar year prior to and the calendar year after diagnosis, from 31,319 to 23,924 for colon cancer patients and from 32,636 to 22,647 for rectal cancer patients, and earnings never fully recovered during the 5-year follow-up. Disposable income was practically unaltered. The probability of work loss increased in the calendar year of diagnosis, from 29.8% to 25.3% the previous year to 83.3% and 84.4% for colon and rectal cancer patients respectively, and never fully recovered. The probability of work loss was similar between colon and rectal cancer survivors, but was higher among patients with rectal cancer who had received neoadjuvant therapy. Interpretation This study shows that despite an extensive welfare system providing maintained disposable income, there is a financial burden in the form of increased risk of work loss and a reduction in earnings among survivors of colorectal cancer. Funding The study was supported by the Swedish Cancer Society, the Swedish Cancer and Allergy Foundation, and the Stockholm Cancer Society, and supported by grants provided by the Regional Agreement on Medical Training and Clinical Research (ALF) between the Stockholm County Council and Karolinska Institutet. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

AIM:The primary therapeutic option for anal cancer treatment is chemoradiotherapy resulting in 80% survival. The aim of this study was to assess long-term bowel function impairment and anal pain at 3 and 6 years after anal cancer diagnosis, based on a hypothesis of an increase in impairment over time. A secondary aim was to investigate if chemoradiotherapy increased the risk for bowel impairment, compared to radiotherapy alone. METHOD:The ANal CAncer study (ANCA) consists of a national Swedish cohort of patients diagnosed with anal cancer between 2011-2013. Patients within the study were invited to respond to a study-specific questionnaire at 3- and 6-years after diagnosis. Descriptive analyses for the primary endpoint and ordinal logistic regressions for secondary endpoint were performed. RESULTS:A total of 388 patients (84%) were included in the study. At 3 years of follow-up, 264 patients were alive. A total of 195 of these patients (74%) answered a study specific questionnaire, and at 6 years 154 patients (67%). Fifty-seven percent experienced bowel urgency at both 3 and 6 years. There was an increased risk for repeated bowel movement within 1 h (OR 2.44 [95% CI: 1.08-5.61, p = 0.03]) at 3 years in patients who had been treated by chemoradiation compared to radiotherapy alone. CONCLUSIONS:Impairment in bowel function and anal pain after anal cancer treatment should be expected and remains after 6 years. This suggests that long-term follow-up may be necessary in some form after customary follow-up. The addition of chemotherapy increases long-term side effects of bowel function.

PurposeUltra-hypofractionated (UHF) radiation therapy (RT) has become a treatment alternative for patients with localized prostate cancer. In more advanced cases, seminal vesicles (SV) are routinely included in the target volume. The Scandinavian HYPO-RT-PC trial, which compared 42.7Gy in 7 fractions (fr) to conventional fractionation (CF), did not include SV in the CTV. The primary objective of the present work is to implement a UHF simultaneous integrated boost (SIB) for prostate cancer RT, incorporating SV into the target volume based on this fractionation schedule. A secondary objective is to analyze the unintentional dose coverage of SV from state-of-the-art VMAT treatments to the prostate gland only.Material and MethodsTwo different equi-effective UHF-SIB treatment schedules to SV were derived based on the CF clinical schedule (50.0Gy/25fr to elective SV and 70.0Gy/35fr to verified SV-invasion (SVI)) using the linear quadric model with α/β=2Gy and 3Gy. The dose to the prostate was 42.7Gy/7fr in both schedules with 31.2Gy/37.8Gy (α/β=2Gy) and 32.7Gy/40.1Gy (α/β=3Gy) to elective SV/verified SVI. VMAT plans to the proximal 10mm and 20mm were optimized and dose-volume-metrics for target volumes and organs at risk (OAR) evaluated.ResultsDose metrics were overall lower for UHF-SIB compared to CF. QUANTEC based volume-criteria are 2-7% lower for rectum and 2-4% lower for bladder in the UHF-SIB. D98% to elective SV were 7-12Gy3 lower with UHF-SIB and the corresponding data for verified SVI were about 2-3Gy3. The SV(10mm) V90%/(29.5Gy) for prostate only treatments (42.7Gy) were in median (IQR) 99% (87-100)/ 78% (58-99) for CTV/PTV.ConclusionUHF RT, based on the HYPO-RT-PC fractionation schedule, with a SIB technique to the prostate and the base of the SV can be planned with lower doses (EQD2) to OARs compared to CF. Unintentional dose to the proximal parts of SV in prostate only treatment can be substantial.