Quality of Life Assessment After Concurrent Chemoradiation for Invasive Bladder Cancer: Results of a Multicenter Prospective Study (GETUG 97-015)

doi:10.1016/j.ijrobp.2009.10.038

International Journal of Radiation OncologyBiologyPhysics

Volume 79, Issue 1, 1 January 2011, Pages 172-178

Presented at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, October 19–23, 2003, Salt Lake City, UT.

https://doi.org/10.1016/j.ijrobp.2009.10.038 Get rights and content

Purpose

To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial.

Patient and Methods

Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment.

Results

Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52–79%) of patients. Overall survival was 36% (95% confidence interval, 23–49%) at 8 years for all patients, and 45% (28–61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6–36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months.

Conclusions

Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients.

Introduction

Although radical cystectomy remains the standard treatment for muscle-invasive bladder cancer, concurrent chemoradiotherapy offers a curative option to patients medically unfit for radical surgery and an alternative conservative treatment for selected patients who are potential candidates for cystectomy. High rates of local control and bladder preservation have been reported with transurethral resection (TUR) followed by chemotherapy used concurrently with radiotherapy 1, 2, 3, 4, 5, 6. There is, however, a need to assess the quality of bladder conservation and other late effects of this treatment strategy. Retrospective studies have reported excellent functional results (7), but the quality of life (QoL) after concurrent radiotherapy and chemotherapy has only been assessed prospectively in one Phase I trial of concurrent gemcitabine and total bladder irradiation (8).

In this prospective study, we analyzed the outcome of 51 patients who received concurrent cisplatin, fluorouracil, and radiotherapy for muscle-invasive bladder cancer, in terms of bladder conservation, global health status, and bladder, bowel, and erectile functions.

Section snippets

Patients

From January 1999 to October 2001, 53 patients from seven institutions were included in a prospective study of concurrent radiotherapy, cisplatin, and 5-fluorouracil. Eligibility criteria were as follows: (1) nonmetastatic, biopsy-proven, muscle-invasive, previously untreated bladder transitional cell carcinoma; (2) normal serum creatinine level; (3) age >18 years; (4) World Health Organization performance status score 0–2; and (5) patient's informed consent. This study obtained the

Patient and tumor characteristics

Patient characteristics are summarized in Table 1. Median age was 68 years (range, 43–78 years). Forty-five patients were male, 6 female. Tumor stage, according to the 1992 International Union Against Cancer classification, was based on TUR findings. Eleven patients (22%) presented with extravesical invasion (T3 or T4a). Histologic grade was established according to the Broder classification and was available for 49 patients. Most tumors were high grade (96%). Surgical lymphadenectomy was

Discussion

Radical cystectomy is widely considered the most effective treatment for locoregional control of muscle-invasive bladder cancer, but it fails to cure more than 50% of patients owing to metastatic disease and may result in diminished QoL despite progress in the field of bladder reconstruction. From the beginning of the 1990s, many Phase II trials have been performed to evaluate the possibility of conservative treatment for muscle-invasive bladder cancer using concurrent chemoradiotherapy, in

Conclusion

This prospective evaluation supports the published retrospective data suggesting good QoL for those invasive bladder cancer patients managed by bladder preservation after TUR and concurrent chemoradiotherapy. The most frequently reported sequela was an increase in moderate urinary frequency.

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Cited by (84)

Quality of life after definitive treatment for bladder cancer: A systematic review and meta-analysis
2024, Radiotherapy and Oncology
Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients’ perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches.
A systematic review was carried out including all prospective and retrospective studies enrolling patients treated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT).
Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference −0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference −0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches.
Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios.
Bladder-sparing trimodal therapy for muscle invasive bladder cancer
2022, Cancer/Radiotherapie
Les stratégies de préservation d’organe dans la prise en charge des cancers aux stades précoces ou localement avancés répondent à un double objectif: le contrôle de la maladie carcinologique et la préservation de fonction de l’organe touché. Compte tenu de la morbi-mortalité inhérente à la cystectomie et de son retentissement sur la qualité de vie et la fonction mictionnelle notamment, les stratégies de préservation vésicale se sont développées pour la prise en charge du carcinome infiltrant urothélial et, plus particulièrement, le traitement tri-modal, comprenant une résection trans-urétrale de vessie maximaliste suivie d’une chimioradiothérapie. Nous proposons, dans cette revue, de détailler, dans un premier temps, les modalités du traitement trimodal, en présentant les différents schémas de radiothérapie et chimiothérapie validés. Le traitement trimodal est ensuite positionné dans la stratégie thérapeutique, en présentant les avantages et les limites par rapport à la cystectomie chez les patients opérables. Ainsi, malgré l’absence de données comparatives issues d’essais randomisés, les deux approches semblent fournir des résultats carcinologiques comparables chez des patients correctement sélectionnés. Par ailleurs, dans les séries modernes, le taux de cystectomie de rattrapage est d’environ 15 % à 5 ans ; cette cystectomie différée ne semble pas associée à une morbi-mortalité plus importante qu’une cystectomie première. L’accent est également mis sur les données de qualité de vie de ces deux approches. Nous précisons, par la suite, les modalités de sélection des patients pour le traitement trimodal, en analysant les critères clinicopathologiques classiques prédictifs de la réponse à la radio(chimio)thérapie, et en évoquant les biomarqueurs moléculaires innovants encore à l’étude. Finalement, dans l’attente de données comparatives robustes, nous insistons sur la nécessité de développer une collaboration pluridisciplinaire étroite dans le choix et la mise en œuvre de la stratégie thérapeutique, en intégrant le patient dans le processus décisionnel.
Organ-sparing strategies in the management of local or locally advanced cancers meet a dual objective: tumor control and preservation of the function of the involved organ. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, bladder-sparing strategies have emerged for the management of urothelial muscle invasive bladder cancer, mostly through trimodal treatment, which consists in maximal trans-urethral resection of bladder tumor, followed by chemo-radiotherapy. This review presents the modalities of trimodal treatment, before exposing the advantages and limitations of this strategy compared to cystectomy among operable patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide similar oncological results among appropriately selected patients. In modern series, the rate of salvage cystectomy is approximately 15% at 5 years; this delayed cystectomy does not seem to be associated with greater morbidity and mortality as compared to upfront cystectomy. Emphasis is placed in the review on quality of life data of these two approaches. In order to optimize the selection of patients eligible to trimodal therapy, the classical predictive factors of response to radio(chemo)therapy are critically analyzed, with the perspective of innovative molecular biomarkers. Finally, a close multidisciplinary collaboration is needed for the choice and the execution of the therapeutic strategy, and the patient should be fully involved in the decision-making process.
Role of radiotherapy in the management of bladder cancer: Recommendations of the French society for radiation oncology
2022, Cancer/Radiotherapie
Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder
2021, Radiotherapy and Oncology
Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.
In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development’s method to define a consensus strategy.
A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.
The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.
Patient-Reported Outcomes and Health-Related Quality of Life Following Radiotherapy for Bladder Cancer
2021, Clinical Oncology
Citation Excerpt :
None of the studies explored at an individual patient level whether any of the symptom domains are more likely to be associated with impaired QoL. As one would expect, studies have shown a deterioration in QoL at the end of radiotherapy, probably as a result of the acute treatment-related toxicity; this then improves at 6 months with a return near to baseline [2,29]. BC2001 established the benefit of concurrent chemotherapy, improving local control and bladder cancer-specific survival [2].
Bladder cancer is the 11th most common cancer in the UK and with an ageing population the incidence is increasing. There is a relative lack of prospective quality of life (QoL) data evaluating the impact of the illness and treatment on QoL and patient-reported outcomes (PROs). Here we evaluate the available tools to assess QoL and PROs, and summarise the published data evaluating outcomes in patients treated with radiotherapy for muscle-invasive disease. We also discuss some of the recently completed studies and those ongoing that will help to shape future care and assist in decision making for patients and their clinicians.
Plan of the day adaptive radiotherapy for bladder cancer: Dosimetric and clinical results
2021, Cancer/Radiotherapie
Pour tenir compte des variations individuelles anatomiques intrapelviennes en cas d’irradiation des tumeurs de la vessie infiltrant le muscle, la radiothérapie adaptative pourrait présenter un bénéfice dosimétrique et clinique.
Les données de dix patients pris en charge dans notre centre pour une tumeur de la vessie infiltrant le muscle par radiothérapie adaptative du “plan of the day” (PoD) individualisé ont été analysées rétrospectivement. Lors du scanner de planification, les volumes cibles et organes à risque ont été délinéés à différents taux de remplissage vésical, aboutissant à deux ou trois plans de traitement. Des imageries de positionnement ont été utilisées pour la sélection du PoD à chaque fraction. L’objectif était d’évaluer cette approche en termes de couverture du volume cible et d’épargne de dose aux tissus sains avoisinants, en la comparant à la technique de radiothérapie définie comme classique. Les objectifs secondaires concernaient la toxicité et l’efficacité.
La couverture cible était respectée avec le traitement adaptatif de97,3 % pour le volume cible anatomoclinique de la vessie (99,5 ; [60,1–100]) et 98 % pour celui de la vessie et des ganglions (98,6 ; [85,4–100]). S’agissant des organes à risque, le volume de tissu sain épargné était de 43,7 % en moyenne et le volume recevant 45 Gy (V45 Gy) de l’intestin grêle de 43,4cc (35 ; [0–129]) (contre 57,6cc). La dose délivrée dans 50 % (D50) du rectum était en moyenne de 18,7 Gy pour le traitement adaptatif (15,9 ; [2,4–44,1]) contre 17 Gy avec l’approche classique. Avec un recul médian de 2,94 ans (IC₉₅ _% [intervalle de confiance à 95 %] : 0,92-4,02), nous avons constaté trois cas de toxicité de grade 3 (30 %). Aucune toxicité de grade 4 n’a été observée. Les taux de survie globale et de survie sans progression à 2 ans étaient respectivement de 65,6 % (IC₉₅ _%: 26-87,6) et 45,7 % (IC₉₅ _%: 14,3-73).
La radiothérapie adaptative utilisant la bibliothèque de plans (PoD) a permis une réduction du volume de tissu sain irradié tout en maintenant une couverture vésicale similaire, avec une toxicité acceptable.
To account of individual intra-pelvic anatomical variations in muscle invasive bladder cancer (MIBC) irradiation, adaptive radiotherapy (ART) using a personalized plan library may have dosimetric and clinical benefits.
The data from ten patients treated for localized MIBC according to the “plan of the day” (P0oD) individualized ART technique were collected and retrospectively analysed. Target volumes and organs at risk (OAR) were delineated at different bladder fill rates, resulting in two or three treatment plans. Daily Cone-Beam CT (CBCT) was used for the selection of PoD at each fraction. Retrospectively, we delineated rectal, intestinal and target volumes on each CBCT, to assess target volume coverage and dose sparing to healthy tissues. A comparison with the conventional radiotherapy technique was performed. The secondary objectives were toxicity and efficacy.
The target coverage was respected with the adaptive treatment: 97.3% for the bladder Clinical Target Volume (CTV) (99.5; [60.1-100]) and 98% for the bladder + lymph nodes CTV (98.6; [85.4-100]). Concerning OAR, the volume of healthy tissue spared was 43.7% on average and the V45 Gy for the small bowel was 43,4cc (35; [0–129]) (versus 57,6cc). The rectal D50 was on average 18,7 Gy for the adaptive treatment (15.9; [2.4-44.1]) versus 17 Gy with the conventional approach. With a median follow-up of 2.94 years (95% CI: [0.92-4.02]), we observed three grade 3 toxicities (30%). No grade 4 toxicity was observed. The 2-year overall survival and progression-free survival rates were 65.6% (95% CI: [26-87.6]) and 45.7% (95% CI: [14.3-73]), respectively.
The ART technique using a PoD strategy showed a reduction of the irradiated healthy tissue volume while maintaining a similar bladder coverage, with an acceptable rate of toxicity.

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Clinical InvestigationQuality of Life Assessment After Concurrent Chemoradiation for Invasive Bladder Cancer: Results of a Multicenter Prospective Study (GETUG 97-015)

Purpose

Patient and Methods

Results

Conclusions

Introduction

Section snippets

Patients

Patient and tumor characteristics

Discussion

Conclusion

J Urol

Int J Radiat Oncol Biol Phys

J Urol

Int J Radiat Oncol Biol Phys

J Urol

Urology

J Urol

J Urol

Urol Clin North Am

Semin Radiat Oncol

Radiother Oncol

Clinical Investigation
Quality of Life Assessment After Concurrent Chemoradiation for Invasive Bladder Cancer: Results of a Multicenter Prospective Study (GETUG 97-015)