Radiotherapy For Muscle-invasive Bladder Cancer Research Articles

Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer

Purpose/ObjectiveDefinitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT.Material/MethodsThis was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS.Results117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5–89.2) and 46% (95% CI 36.5–57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%.ConclusionPartial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Radiotherapy Use in Muscle-Invasive Bladder Cancer: Review of the Guidelines and Impact of Increased Awareness in Patient Referral at a Tertiary Center in Belgium.

Pronounced underuse of radiotherapy (RT) in muscle-invasive bladder cancer (MIBC) is reported. This study aims to assess the awareness about the role of RT in different MIBC settings and see whether this has increased since 2017. We reviewed the bladder cancer guidelines of the EAU, ESMO, NCCN, NICE, and AUA/ASCO/ASTRO/SUO, focusing on the role of RT in MIBC. In 2017, we evaluated the use of RT in MIBC in Belgium. This raised awareness about the indications of RT in different MIBC settings. Here, we present a retrospective pattern of care analysis of the RT use for MIBC patients at our center from January 2012 until December 2021. Frequency of RT use, patient, disease and treatment characteristics were compared between two 5-year periods (2012-2016 and 2017-2021). Review of the guidelines suggested that RT can be used as a treatment option in most MIBC settings. However, differences between guideline recommendations existed and high-level evidence was often lacking. Overall, 221 unique MIBC patients received RT at our center. RT use for MIBC was 39% higher in the second 5-year period (Between the same periods, the number of new MIBC registrations increased with 26%). The most pronounced increase, ie, 529%, was observed in the primary setting and was in parallel with patient preference becoming the main indication for RT. Participation in clinical trials seems to have had an important impact on the frequency of RT use in the adjuvant and metastatic setting. We provide a critical overview of the RT indications in MIBC as recommended by the international guidelines. Increased awareness about RT as a treatment option in MIBC seems to have an impact on the treatment choice in clinical practice, as was observed in our tertiary center.

Radical radiotherapy for muscle-invasive bladder cancer: A single centre experience.

519 Background: Muscle-invasive bladder cancer (MIBC) is managed with radical cystectomy or (chemo)radiotherapy ((C)RT), CRT offers the chance of cure alongside organ preservation. Patients presenting with MIBC are often elderly and frail, with comorbidities precluding cystectomy and systemic treatment. We report outcome data for our institution of patients treated with radical (C)RT. Methods: Patients with T2-4N0 MIBC diagnosed between December 2014 and December 2021 were retrospectively identified from the radiotherapy planning system. Baseline demographic, clinical and follow up data were collated from electronic patient records. Results: 54 patients were identified. Mean patient age was 78.5 (range 47 – 94); 51 patients had urothelial cancer and 3 squamous cell carcinoma. 20 patients had evidence of carcinoma in situ (CIS) at diagnosis. 19 patients had neoadjuvant chemotherapy (NACT) (13 patients had cisplatin-gemcitabine, 6 patients had carboplatin-gemcitabine). 12/19 patients completed 3 cycles of NACT, 7 patients received 1-2 cycles. 24/54 patients had concurrent chemotherapy (6 patients receiving mitomycin-5-FU, 17 weekly gemcitabine and 1 weekly cisplatin). 14/24 patients completed concurrent chemotherapy as planned. Of the 24 patients treated with CRT, 18 had NACT. 12 patients received 64 Gy 32 fractions, 2 received 60 Gy 30 fractions, and 40 received 55 Gy 20 fractions. All except 1 patient completed the prescribed course. With a median follow up of 9.4 months (range 0.7-79 months), 3-year overall survival was 43% for all patients; 63% with CRT and 21% with RT alone (log-rank test p=0.0052 HR 3.15 (95% CI 1.48-6.7)). At 3 years 49% were free of recurrence (distant or local); 72% with CRT and 25% with RT alone (log-rank test 0.0079 HR 3.12 (95% CI 1.38-7.01)). 3yr OS and % free of recurrence were not impacted by the presence of CIS. OS was 46% with CIS and 41% without (log-rank test p=0.6649); 3yr % free of recurrence was 43% with CIS and 49% without (log-rank test p=0.4055). Median time to recurrence with CIS was shorter at 13.3 months vs 26.1 months. Conclusions: Radical radiotherapy to the bladder is an effective option for the treatment of MIBC and should be routinely discussed with patients. Patients should be treated with CRT as opposed to RT alone as both OS and RFS are significantly improved. Ensuring patients are fit to receive systemic treatment alongside RT may require prehabilitation in this elderly and more co-morbid group.

A Survey of the Real-world Patient-reported Experience of Follow-up Practices Following Radical Surgery or Radiotherapy for Muscle-invasive Bladder Cancer (MIBC)

A Survey of the Real-world Patient-reported Experience of Follow-up Practices Following Radical Surgery or Radiotherapy for Muscle-invasive Bladder Cancer (MIBC)

Optimized Adaptive Radiotherapy with Individualized Plan Library for Muscle-Invasive Bladder Cancer Using Internal Target Volume Generation.

Simple SummaryThe bladder is a mobile target and is subject to filling variation. This poses a considerable challenge for effective radiotherapy (RT) delivery. We applied an internal target volume to the plan library to resolve intra-fractional errors caused by bladder filling during treatment. Adaptive radiotherapy using ITV is easy to perform and a feasible treatment approach. In this study, image-guided RT-based adaptive RT showed good survival outcomes with a high local control rate.The bladder is subject to filling variation, which poses a challenge to radiotherapy (RT) delivery. We aimed to assess feasibility and clinical outcomes in patients with bladder cancer treated with adaptive RT (ART) using individualized plan libraries. We retrospectively analyzed 19 patients who underwent RT for muscle-invasive bladder cancer (MIBC) in 2015–2021. Four planning computed tomography (CT) scans were acquired at 15-min intervals, and a library of three intensity-modulated RT plans were generated using internal target volumes (ITVs). A post-treatment cone-beam CT (CBCT) scan was acquired daily to assess intra-fraction filling and coverage. All patients completed the treatment, with 408 post-treatment CBCT scans. The bladder was out of the planning target volume (PTV) range in 12 scans. The volumes of the evaluated PTV plans were significantly smaller than those of conventional PTV. The 1-year and 2-year overall survival rates were 88.2% and 63.7%, respectively. Of eight cases that experienced recurrence, only two developed MIBC. There were no grade 3 or higher RT-related adverse events. ART using plan libraries and ITVs demonstrated good survival outcomes with a high local control rate. Irradiated normal tissue volume and treatment margins may be reduced through this approach, potentially resulting in lower toxicity rates.

Mapping Local Failure Following Bladder Radiotherapy According to Dose

AimsTo determine the relationship between local relapse following radical radiotherapy for muscle-invasive bladder cancer (MIBC) and radiation dose. Materials and methodsPatients with T2-4N0-3M0 MIBC were recruited to a phase II study assessing the feasibility of intensity-modulated radiotherapy to the bladder and pelvic lymph nodes. Patients were planned to receive 64 Gy/32 fractions to the bladder tumour, 60 Gy/32 fractions to the involved pelvic nodes and 52 Gy/32 fractions to the uninvolved bladder and pelvic nodes. Pre-treatment set-up was informed by cone-beam CT. For patients who experienced local relapse, cystoscopy and imaging (CT/MRI) was used to reconstruct the relapse gross tumour volume (GTVrelapse) on the original planning CT . GTVrelapse D98% and D95% was determined by co-registering the relapse image to the planning CT utilising deformable image registration (DIR) and rigid image registration (RIR). Failure was classified into five types based on spatial and dosimetric criteria as follows: A (central high-dose failure), B (peripheral high-dose failure), C (central elective dose failure), D (peripheral elective dose failure) and E (extraneous dose failure). ResultsBetween June 2009 and November 2012, 38 patients were recruited. Following treatment, 18/38 (47%) patients experienced local relapse within the bladder. The median time to local relapse was 9.0 months (95% confidence interval 6.3–11.7). Seventeen of 18 patients were evaluable based on the availability of cross-sectional relapse imaging. A significant difference between DIR and RIR methods was seen. With the DIR approach, the median GTVrelapse D98% and D95% was 97% and 98% of prescribed dose, respectively. Eleven of 17 (65%) patients experienced type A failure and 6/17 (35%) patients type B failure. No patients had type C, D or E failure. MIBC failure occurred in 10/17 (59%) relapsed patients; of those, 7/11 (64%) had type A failure and 3/6 (50%) had type B failure. Non-MIBC failure occurred in 7/17 (41%) patients; 4/11 (36%) with type A failure and 3/6 (50%) with type B failure. ConclusionRelapse following radiotherapy occurred within close proximity to the original bladder tumour volume and within the planned high-dose region, suggesting possible biological causes for failure. We advise caution when considering margin reduction for future reduced high-dose radiation volume or partial bladder radiotherapy protocols.

Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy

PurposeWe report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy. Materials and MethodsThe study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score. ResultsOf the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3–18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16–9.73, P = 0.02) and 5.27 (95% CI 1.87–14.84, P = 0.002) for IR and HR respectively, with LR as reference. ConclusionLRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC.

Three-Dimensional Conformal Radiotherapy with Concomitant Boost and Weekly Cisplatin in Muscle-Invasive Transitional Cell Bladder Carcinoma

Abstract Background: Local control of MIBC by bladder-sparing approach is unsatisfactory. In order to improve the effectiveness of radiotherapy, we have designed a protocol that combines TURB with a non-conventionally fractionated radiotherapy “concomitant boost. Aim of Study: To evaluate the response rate and toxicity criteria in patients with transitional cell bladder cancer treated with maximum Transurethral Resection (TUR), followed by 3-D conformal radiotherapy with a concomitant boost and weekly cisplatin with shortening of overall treatment time. Patients and Methods: Between July 2017 to June 2018, 20 patients with a T2-T3 N0M0 transitional cell carcinoma of the bladder underwent transurethral resection of bladder tumor as much as safely possible (maximum TURBT). They received radiotherapy delivered in short overall treatment time with a concomitant boost technique. With this technique, a dose of 40Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus a margin of 15Gy in fractions of 0.75Gy. The total tumor dose was 55Gy in 20 fractions in 4 weeks. Weekly Cisplatin (30mg/m2) was administered weekly concurrently with radiotherapy. Cisplatin was interrupted in case of hema-tological or renal toxicity. The National Cancer Institute Common Toxicity Criteria, version 5, scale was used to assess the chemotherapy and acute radiation toxicity {Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, November 2017}. We assessed late toxicity using The Radiation Therapy Oncology Group/The European Organiza-tion for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Scheme. Results: The feasibility of the treatment was good. Severe acute toxicity >!G3 was observed in two patients (10%). Severe late toxicity >!G3 was observed in one patient (5%). Fourteen patients (70%) showed a complete and three (15 %) a partial remission after treatment. Conclusion: In external radiotherapy for muscle-invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity.

22 Outcomes and Profiles of Elderly Patients Receiving Definitive Radiotherapy for Muscle-Invasive Bladder Cancer at a Tertiary Medical Center in U.S.A.

22 Outcomes and Profiles of Elderly Patients Receiving Definitive Radiotherapy for Muscle-Invasive Bladder Cancer at a Tertiary Medical Center in U.S.A.

MRE11A Isoform Expression Associated with Outcome Following Radiotherapy in Muscle-Invasive Bladder Cancer does not Alter Cell Survival and DNA Double-Strand Break Repair Following Ionising Radiation.

Background:DNA double strand breaks are the cytotoxic lesions produced by ionising radiation. Critical for the repair of these lesions is the DNA damage response protein MRE11 which, in a complex with RAD50 and NBS1, mediates DNA damage signalling and double-strand break repair. We previously found the presence of an MRE11 germline single nucleotide polymorphism (SNP), rs1805363 (G > A), to be associated with poor outcome following radiotherapy (RT) and increased expression of MRE11 isoform 2 in a limited panel of bladder cancer cell lines and tumours.Objectives:To look for further evidence in support of the SNP/isoform association in a larger panel of germline and tumour samples donated by patients diagnosed with invasive bladder cancer, and to test the hypothesis that bladder cancer cells expressing MRE11 isoform 2 would be more radio resistant than cells expressing MRE11 isoform 1.Methods:Germline DNA from 189 patients with invasive bladder cancer (141 T2, 48 T1) was genotyped for the rs1805363 G > A SNP. Loss of heterozygosity was determined by genotyping tumour DNA in 17GA germline patients. The Cancer Genome Atlas was mined to correlate presence of the GA germline genotype with MRE11 isoform expression. We used colony formation assays and γH2AX foci kinetics after ionising radiation in RT112 MRE11 knockdown cells expressing ectopic MRE11 isoform 1 or 2.Results:Of the 189 germline DNA samples, 22 contained both the A minor allele and G major allele with the remaining wild type containing only the G major allele. LOH was identified in seven of 17 available tumour samples. Tumour MRE11 isoform 2 expression was found to be significantly higher (p = 0.007) in patients’s samples containing the A minor allele compared to those with only the G major allele (n = 23). In the TCGA database we found 16% (66 out of 406) of bladder tumours heterozygous for the SNP and only two homozygous, and a significant relative increase of isoform 2 usage (p = 0.017). We identified no significant difference in radio sensitivity between bladder cancer cells expressing either MRE11 isoform.Conclusions:In this study the MRE11 isoform 2 was not found to be associated with increased cellular sensitivity to radiation. We conclude that the previously reported association between the germline rs1805363 SNP and poor survival in MIBC patients following RT is unlikely to be related to the DNA damage response function of MRE11 isoform 2.

Evaluating the Current Place of Radiotherapy as Treatment Option for Patients With Muscle Invasive Bladder Cancer in Belgium.

There is a gap between optimal and actual use of radiotherapy (RT) in muscle-invasive bladder cancer (MIBC). We investigated the opinions of radiation-oncologists, urologists, and medical oncologists on use of RT in different cases. Barriers and facilitators for applying guidelines were examined. A web-based survey was developed at Ghent University Hospital and conducted from November 18, 2016 to July 17, 2017. The place of primary, adjuvant, and palliative RT was evaluated. Additional questions assessed the use of guidelines, barriers, and facilitators. In total, 126 physicians (57 radiation oncologists, 41 urologists, and 28 medical oncologists) completed the survey. Significant differences in use of RT in the primary and adjuvant setting were observed between radiation oncologists and urologists. Younger age and presence of hydronephrosis are perceived as contraindications for RT in the primary setting. In the adjuvant setting, RT was mainly considered in case of positive surgical margins. All radiation oncologists and 96% of medical oncologists considered palliative RT for patients with painful bone metastases, whereas 21% of urologists did not (P< .001). Clinical decisions are mainly based on EAU guidelines. The most important reason for nonadherence to guidelines is external barriers (18%). One strategy to improve awareness of guidelines is a summary of guidelines on the website of national organizations (54%). There is controversy regarding the place of RT in MIBC, with a clear variation between professionals. Barriers and facilitators to use RT should be addressed, seeing the gap in RT utilization and predicted increase in patients requiring RT for MIBC.

Routine bladder cancer treatment dictates divergence from trial-derived regimens: Results of treatment at 44 radiotherapy centers

PurposeTo assess characteristics and outcome of patients treated with radiotherapy for muscle-invasive bladder cancer at 44 community-based radiotherapy centers and compare these to those on clinical trials. Materials and methodsWe reviewed 155 patients who had been treated from 2010 to 2014. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Results were compared to a pooled analysis of 6 Radiation Therapy Oncology Group (RTOG) protocols. ResultsWhat stood out was that our patients' characteristics were significantly inferior than those on RTOG studies: lower rate of complete transurethral resection of bladder tumor: 36.8% vs. 70% (P<0.0001), higher median age: 79 years vs. 66 (P<0.0001), more medically inoperable: (51.0%) vs. 0% in RTOG (P<0.001), and 46.9% had refused surgery. Fewer patients underwent concurrent chemotherapy: 56.1% vs. 100% (P<0.0001). It was also striking that at median follow-up 12.6 months (range: 3.1–49.2), the 36-month overall survival was 51.3% for those who refused surgery vs. 24.5% for medically inoperable (P = 0.009); 58.1% with complete transurethral resection of bladder tumor vs. 29.8% if incomplete (P = 0.07); 54.3% with chemoradiotherapy (CRT) vs. 17.2% without (P = 0.03); 66.3% for those who refused surgery and had CRT vs. 38.9% for medically inoperable who had CRT (P = 0.04). ConclusionsThe cohort at community-based centers was older, more medically inoperable, and less likely to receive CRT than clinical trial patients. This suggests that we may not be able to apply trial-derived regimens for many patients in this setting. There is a pressing need to find treatment options for such patients, especially given the aging population. Survival of medically operable CRT patients was comparable to results of RTOG protocols notwithstanding this study's smaller sample size, retrospective nature and suboptimal documentation of patient characteristics.

The Use of External-beam Radiotherapy for Muscle-invasive Bladder Cancer in Elderly or Medically-fragile Patients.

To evaluate the clinical results of external-beam radiotherapy (EBRT) for muscle-invasive bladder cancer (MIBC) in elderly or medically-fragile patients. Twenty-five consecutive patients with MIBC (cT2-4N0-1M0) receiving EBRT were retrospectively analyzed. Their median age was 82 years. Radiotherapy median dose was 60 Gy administered in 30 fractions. Median follow-up period was 14.7 months. Median overall survival (OS) and progression-free survival (PFS) were 14.7 months and 7.8 months, respectively. The OS, cause-specific survival (CSS), and PFS rates at 1-year were 56.0%, 68.5%, and 40.0%, respectively. The local progression-free rates (LPFR) at 6 months and 1 year were 89.3% and 59.5%, respectively. Performance status 3 was a significantly unfavorable factor for OS, CSS, and progression-free survival; clinical N stage was a significantly unfavorable factor for progression-free survival; and lower irradiation dose (≤50.4 Gy) was a significantly unfavorable factor for LPFR. EBRT for elderly or medically-fragile patients is feasible, and achieves acceptable local progression-free status.

Bladder-sparing radiotherapy for muscle-invasive bladder cancer: A survey of providers to determine barriers and enablers

BackgroundTo understand barriers and enablers to use of curative-intent radiotherapy (RT) for muscle-invasive bladder cancer using the Theoretical Domains Framework (TDF). MethodsCanadian urologists, radiation oncologists (ROs) and medical oncologists (MOs) participated in a web-based survey to assess barriers and enablers to use of RT. Survey questions were thematically mapped to TDF domains. Logistic regression was used to identify TDF domains associated with high referral/use of RT. Results64 urologists, 29 ROs and 26 MOs participated. Participants reported comparable survival at five years with cystectomy (51%) and RT with concurrent chemotherapy (50%). Despite this, participants reported low RT referral/treatment rates: Urologists referred a median of 2/10 patients to RO; ROs treated a median of 5/10 patients referred; and MOs referred a median of 2/8 patients not referred to RO by urology. Among urologists, the TDF domains ‘beliefs about consequences’ (OR=8.1, 95% CI 1.5–44.9), ‘social and professional role’ (OR=11.2, 95% CI 2.3–53.6) and ‘environmental context and resources’ (OR=5.9, 95% CI 1.5–23.3) were associated with higher rates of RO referral. ConclusionsWe have identified factors associated with referral for RT among patients with bladder cancer. These factors should be addressed as part of a concerted effort to increase utilization of RT.

Bladder-sparing Radiotherapy for Muscle-invasive Bladder Cancer: A Qualitative Study to Identify Barriers and Enablers

AimsBladder-sparing radiotherapy for muscle-invasive bladder cancer (MIBC) may be underutilised in North America. To understand factors driving practice we used the Theoretical Domains Framework (TDF) to identify barriers and enablers of bladder-sparing radiotherapy utilisation. Materials and methodsA convenience sample of Canadian urologists, medical oncologists and radiation oncologists participated in individual semi-structured 1 h interviews. An interview guide was developed using the TDF to assess barriers and enablers of bladder-sparing radiotherapy use. Interviews were recorded and transcribed. Two investigators independently identified barriers and enablers and assigned them to specific themes. Participant recruitment continued until saturation. ResultsIn total, 71 physicians were invited to participate and 34 (48%) agreed to be interviewed; 13 urologists, 11 radiation oncologists and 10 medical oncologists. We identified the following barriers to the use of bladder-sparing radiotherapy (relevant TDF domains in parentheses): (1) beliefs that radiotherapy has inferior survival compared with cystectomy (beliefs about consequences); (2) lack of referral from urology to radiation oncology (behavioural regulation; memory, attention and decision-making); (3) lack of ‘champions’ who advocate for radiotherapy (social and professional role); and (4) inadequate multidisciplinary collaboration (environmental context and resources). Predominant enablers to the use of bladder-sparing radiotherapy included: (1) ‘champions’ who believe in the value of radiotherapy (social and professional role); (2) beliefs by urologists that radiation oncologists should present radiotherapy options to all patients (social and professional role); (3) institutional policy that all MIBC patients should be seen by multiple specialists (environmental context and resources); (4) system facilitators of radiation oncology referral (i.e. nurse navigator) (environmental context and resources); and (5) patient-driven consultations seeking alternatives to cystectomy (social influences). ConclusionsThese findings identify important barriers and enablers to the use of bladder-sparing radiotherapy in MIBC. Physician beliefs, access to multidisciplinary care and institutional context should be considered in efforts to increase the use of bladder-sparing radiotherapy.

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

Background:The majority of anal cancers (84–95%) are driven by infection with human papillomavirus (HPV). HPV-positive tumours show significantly better responses to chemo-radiotherapy when compared with HPV-negative tumours. HPV infection is linked to alterations in DNA damage response proteins, including MRE11. MRE11 is a potential predictive biomarker for response to radiotherapy in muscle-invasive bladder cancer and may hold predictive power in other cancers.Methods:Using a previously reported cohort, we evaluated the levels of MRE11 in anal cancer and assessed its predictive value in this disease.Results:We found no association between the level of MRE11 and relapse-free survival following chemo-radiotherapy.Conclusions:MRE11 has no predictive value in the analysis of relapse-free survival after chemo-radiotherapy in anal cancer and does not add to the prognostic value of p16 and tumour-infiltrating lymphocyte scores. Further investigation into the role of DNA repair proteins in anal cancer is required.

BC2001 long-term outcomes: A phase III randomized trial of chemoradiotherapy versus radiotherapy (RT) alone and standard RT versus reduced high-dose volume RT in muscle-invasive bladder cancer.

280 Background: BC2001 showed that adding chemotherapy (5FU+MMC) to radiotherapy significantly improved rates of muscle invasive bladder cancer (MIBC) locoregional control (LRC) [James 2012] but that reduced high dose volume RT rather than standard RT did not significantly reduce late side effects [Huddart 2013]. Here we present an update of the time to event outcomes after a median 10 years follow up. Methods: Under the 2x2 partial factorial design, 458 pts were randomised to RT (178) or cRT (182) (CT comparison) and/or to stRT (108) or RHDVRT (111) (RT comparison). Primary endpoint was LRC, secondary endpoints included overall survival (OS), bladder-cancer specific survival (BCSS), metastasis free survival (MFS) and salvage cystectomy rates. Results: Median follow up was 118 months (95%CI: 112-122). LRC and invasive LRC (ILRC) were improved with cRT (Table 1). Though no statistically significant differences between groups were found in OS, cRT exhibited a trend towards improvement in BCSS, significant when adjusted by known prognostic factors. Similar trend was found for MFS. Salvage cystectomy rate was lower for cRT (2-year rate, cRT:11% vs RT:17%, p=0.03). No differences between stRT and RHDVRT were found for any trial endpoint. Conclusions: With extended follow-up, an improvement in LRC and a reduced salvage cystectomy rate is confirmed with cRT. After adjustment for known prognostic factors this results in an improvement in BCSS. This updated data supports the use of cRT with 5FU/MMC and confirms this should be a standard of care for this patient population. Clinical trial information: ISRCTN68324339. [Table: see text]

Radiotherapy for Muscle-invasive Bladder Cancer in Very Elderly Patients.

The standard therapy for muscle invasive bladder cancer (MIBC) is radical total cystectomy; however, radiotherapy (RT) is performed in patients who cannot tolerate surgery due to advanced age. This study aimed to retrospectively examine whether the feasibility of concurrent use of intra-arterial chemotherapy (IAC) can be assessed using both treatment results of RT for MIBC in elderly patients and the G8 Screening Tool. We studied 16 patients who had received intra-arterial chemoradiotherapy (IACRT) or RT alone between February 2004 and December 2012. The median age was 83 (range=75-91) years. Twelve patients had stage II and 4 had stage III disease. Ten patients received IACRT and six received RT alone. In order to determine whether the G8 score distinguishes patients for treatment with IACRT or RT alone, we calculated the cut-off of the G8 score for addition of IAC. The overall median G8 score was 12 (range=9-15), with scores of 13 (range=12-15) in the IACRT group and 10 (range=9-11) in the RT-alone group. The G8 score was 12 or more in all patients in the IACRT group. The median follow-up period was 35 (range=6-64) months. The 2- and 5-year overall survival rates were 80% and 66.7% in the IACRT group. The 1- and 2-year survival rates in the RT-alone group were 50% and 25%, respectively. Regarding late adverse events, only one patient experienced grade 2 genitourinary toxicity. IACRT was considered to be useful for the treatment of MIBC in elderly patients, with tolerable adverse events. Moreover, used in conjunction with age and performance status, the G8 Screening Tool is potentially applicable for determining the feasibility of performing IAC. To our knowledge, this is the first report about the correlation between G8 score and feasibility of IAC.

EXD2 - a new player joins the DSB resection team

EXD2 - a new player joins the DSB resection team

Quality of Life Outcomes for Bladder Cancer Patients Undergoing Bladder Preservation with Radiotherapy.

For patients with muscle-invasive bladder cancer, the decision to undergo radical cystectomy or bladder preservation treatment must incorporate survival differences, toxicity, and quality of life. Our objective was to review patient-reported outcomes for bladder preservation treatment with a focus on patients eligible for radical cystectomy, for whom a comparison of patient-reported outcomes is most relevant. Peer-reviewed, English-language manuscripts in MEDLINE and PubMed databases were examined from 1996 through 2014. Subject headings included quality of life, bladder cancer, bladdersparing, bladder preservation, radiation, and radiotherapy. Prospective and retrospective studies of patient-reported outcomes in patients undergoing bladder preservation with radiotherapy for muscle-invasive bladder cancer were included. Two prospective studies and four retrospective studies were identified. Several weaknesses from these studies were identified including small sample sizes, variable time points of assessment, variation in treatment regimens, and failure to use validated or condition-specific questionnaires. From the available data, bladder preservation appears to result to similar or better general quality of life compared to radical cystectomy with satisfactory urinary and sexual function reported in most series. In general, bladder preservation resulted in more gastrointestinal symptoms than radical cystectomy. This is one of the first reviews on the subject of patient-reported outcomes for bladder preservation in muscle-invasive bladder cancer. Although the data are limited, this review may provide a framework for developing well-designed, prospective comparisons of treatment for this patient cohort.