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Sequential Chemotherapy Followed by Ultrahypofractionated Radiotherapy for Muscle-Invasive Bladder Cancer

29 ottobre 2026 aggiornato da: Walaa Khalifa Fathy Mohammed, Assiut University

Sequential Chemotherapy Followed by Ultrahypofractionated Radiotherapy for Muscle-Invasive Bladder Cancer in Older Adults: Clinical Outcomes and Treatment-Related Toxicity

Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease for which radical cystectomy with appropriate systemic therapy remains a standard curative approach in medically fit patients. . However, Half of bladder cancer cases are diagnosed in patients aged over 75 years, many of whom are not fit for major surgery owing to their performance status and comorbidities .

A substantial proportion of bladder cancer cases occur in older adults (there is no single universal age cutoff for the term older adults, but several commonly used definitions exist: WHO: generally refers to people aged 60 years or older, particularly in low- and middle-income countries, while in clinical and research settings: ≥65 years is frequently used as the operational definition of older adults, especially in oncology and geriatric medicine), and advanced age is frequently accompanied by comorbidities and frailty that may limit eligibility for radical surgery or multimodality treatment . Bladder-preserving treatment incorporating maximal transurethral resection of bladder tumor (TURBT) and definitive radiotherapy is therefore an important treatment option in selected patients.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease for which radical cystectomy with appropriate systemic therapy remains a standard curative approach in medically fit patients. However, Half of bladder cancer cases are diagnosed in patients aged over 75 years, many of whom are not fit for major surgery owing to their performance status and comorbidities .

A substantial proportion of bladder cancer cases occur in older adults (there is no single universal age cutoff for the term older adults, but several commonly used definitions exist: WHO: generally refers to people aged 60 years or older, particularly in low- and middle-income countries, while in clinical and research settings: ≥65 years is frequently used as the operational definition of older adults, especially in oncology and geriatric medicine), and advanced age is frequently accompanied by comorbidities and frailty that may limit eligibility for radical surgery or multimodality treatment. Bladder-preserving treatment incorporating maximal transurethral resection of bladder tumor (TURBT) and definitive radiotherapy is therefore an important treatment option in selected patients.

Most established bladder-preservation protocols use concurrent chemoradiotherapy. Nevertheless, sequential treatment-systemic chemotherapy followed by definitive radiotherapy-may be attractive in selected patients . Published data support bladder-preserving radiotherapy in older adults, although the literature is heterogeneous and most contemporary series evaluate concurrent rather than purely sequential treatment . In Older adults, concurrent chemoradiotherapy has been associated with improved survival, while hypofractionated bladder radiotherapy schedules have demonstrated acceptable tolerability in selected older populations .

These observations provide the rationale for prospectively evaluating a sequential approach in patients who are not ideal candidates for concurrent chemoradiotherapy. A number of small single-centre studies using the higher biological dose of 30-36 Gy in 6 Gy per fraction suggest acceptable acute and late toxicity with local control achieved in over of 60% patients at 3 months . Prospective multicentre assessment of this radiotherapy schedule has not yet been performed. The proposed study will evaluate the feasibility, efficacy, treatment completion, and toxicity of a sequential strategy in older adults with non-metastatic MIBC.

Tipo di studio

Interventistico

Iscrizione (Stimato)

Fase

Fase 3

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

65 anni e precedenti (Adulto più anziano)

Accetta volontari sani

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

Histologically confirmed urothelial carcinoma of the urinary bladder
Muscle-invasive disease, preferably clinical stage cT2-T4a, N0, according to TNM staging system.
No evidence of distant metastatic disease (M) .
Age ≥65 years including medically unfit patients for radical cystectomy or radical daily radiotherapy for any reason including but not limited to performance status, comorbidity or patient preferance .
ECOG performance status 0_ 3.
Patients must have undergone maximal safe TURBT, with documentation of detrusor muscle in the specimen whenever technically feasible.
_Creatinine clearance (CrCl) ≥30 mL/min for patients receiving a carboplatin-based regimen.

CrCl ≥40 mL/min for patients receiving fractionated cisplatin-based chemotherapy.

8- Eligible patients would have an expected survival of greater than 6 months, be willing to accept assessment with cystoscopy following radiotherapy completion and be able to attend for follow-up

Exclusion Criteria:

Nodal disease and distant metastatic disease (M1).
Previous radiotherapy to the pelvis or any contraindication for pelvic RT including IBD.
Previous systemic chemotherapy for the current MIBC.
Uncontrolled active infection, moderate to severe hydronephrosis, invasion of prostatic urethra, diffuse TIS throughout the bladder, tumor size >6 cm.
Active or history of other malignancy within 2 years of recruitment except for non-melanomatous skin carcinoma, previous non-muscle invasive bladder tumors and low-risk prostate cancer (as defined by NCCN risk stratification as T1/T2a, Gleason 6, PSA <10) will be excluded.
_ Active Hepatitis B and Hepatitis C.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Scopo principale: Trattamento
Assegnazione: N / A
Modello interventistico: Assegnazione di gruppo singolo
Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm Gruppo di partecipanti / Arm Un gruppo o sottogruppo di partecipanti a uno studio clinico che riceve un intervento/trattamento specifico o nessun intervento, secondo il protocollo dello studio.	Intervento / Trattamento Intervento / Trattamento Un processo o un'azione che è al centro di uno studio clinico. Gli interventi includono farmaci, dispositivi medici, procedure, vaccini e altri prodotti sperimentali o già disponibili. Gli interventi possono anche includere approcci non invasivi, come l'educazione o la modifica della dieta e dell'esercizio fisico.
Sperimentale: Older adults with muscle invasive bladder cancer Patients aged ≥65 years with histologically confirmed muscle-invasive urothelial carcinoma of the urinary bladder with non-metastatic disease and with PS 0-3, who are medically unfit or unsuitable for radical cystectomy or radical conventional RT, will be treated with sequential chemotherapy followed by ultrahypofractionated radiotherapy will be considered for enrollment.	Procedura: Transurethral Resection of Bladder Tumor All patients should undergo maximal safe TURBT before systemic treatment. The objective is maximal tumor debulking while preserving bladder function and obtaining adequate tissue for pathological diagnosis and staging. A second-look TURBT may be considered, especially when the initial resection was incomplete (tumors ≥3 cm, no evaluation of muscle involvement in spite of radiological evidence). Droga: Sequential Systemic Chemotherapy Systemic chemotherapy will be administered before radiotherapy. The preferred regimen should be selected according to renal function, performance status, comorbidities, and multidisciplinary assessment. Suggested protocol options: Cisplatin-eligible patients: Gemcitabine + cisplatin may be used commonly for 3-4 cycles. Cisplatin-ineligible patients: Gemcitabine + carboplatin may be considered where appropriate . Radiotherapy should commence after adequate recovery from chemotherapy, provided there is no evidence of progression and the patient remains suitable for local treatment. A practical interval is approximately 3-6 weeks after the final chemotherapy cycle. Radiazione: radiotherapy Three-dimensional conformal radiotherapy planning is recommended using three or four fields; however, use of static 5-7-field IMRT or volumetric modulated arc radiotherapy treatment is permitted. Three-dimensional dose distributions will be produced for the overall prescribed dose of 36 Gy in six fractions. The dose distribution will be assessed for coverage of the PTV and normal tissues sparing using appropriate transverse sagittal and coronal views. All plans will be created to ensure that at least 98% of the PTV (PTV D98%) receives >90% (ideally >95%) of the prescribed dose, the median PTV dose (PTV D50%) is within 1% of the prescription dose and the near maximum (PTV D2%) is <107% (ideally <105%) of the prescribed dose. To minimize unexpected high dose outside the PTV, it is required that 1 cm3 of normal tissue outside the PTV should be <110% of the prescribed dose.

Gruppo di partecipanti / Arm

Intervento / Trattamento

Sperimentale: Older adults with muscle invasive bladder cancer

Patients aged ≥65 years with histologically confirmed muscle-invasive urothelial carcinoma of the urinary bladder with non-metastatic disease and with PS 0-3, who are medically unfit or unsuitable for radical cystectomy or radical conventional RT, will be treated with sequential chemotherapy followed by ultrahypofractionated radiotherapy will be considered for enrollment.

Procedura: Transurethral Resection of Bladder Tumor

All patients should undergo maximal safe TURBT before systemic treatment. The objective is maximal tumor debulking while preserving bladder function and obtaining adequate tissue for pathological diagnosis and staging. A second-look TURBT may be considered, especially when the initial resection was incomplete (tumors ≥3 cm, no evaluation of muscle involvement in spite of radiological evidence).

Droga: Sequential Systemic Chemotherapy

Systemic chemotherapy will be administered before radiotherapy. The preferred regimen should be selected according to renal function, performance status, comorbidities, and multidisciplinary assessment.

Suggested protocol options:

Cisplatin-eligible patients: Gemcitabine + cisplatin may be used commonly for 3-4 cycles.
Cisplatin-ineligible patients: Gemcitabine + carboplatin may be considered where appropriate .

Radiotherapy should commence after adequate recovery from chemotherapy, provided there is no evidence of progression and the patient remains suitable for local treatment. A practical interval is approximately 3-6 weeks after the final chemotherapy cycle.

Radiazione: radiotherapy

Three-dimensional conformal radiotherapy planning is recommended using three or four fields; however, use of static 5-7-field IMRT or volumetric modulated arc radiotherapy treatment is permitted.

Three-dimensional dose distributions will be produced for the overall prescribed dose of 36 Gy in six fractions. The dose distribution will be assessed for coverage of the PTV and normal tissues sparing using appropriate transverse sagittal and coronal views.

All plans will be created to ensure that at least 98% of the PTV (PTV D98%) receives >90% (ideally >95%) of the prescribed dose, the median PTV dose (PTV D50%) is within 1% of the prescription dose and the near maximum (PTV D2%) is <107% (ideally <105%) of the prescribed dose. To minimize unexpected high dose outside the PTV, it is required that 1 cm3 of normal tissue outside the PTV should be <110% of the prescribed dose.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato	Misura Descrizione	Lasso di tempo
Assessment of objective Response rate (ORR) and Disease control rate (DCR) Lasso di tempo: 4-6 weeks after completion of RT	Evaluate the Clinical efficacy including Objective Response rate (ORR) and Disease control rate (DCR) at 4-6 weeks after finishing RT.	4-6 weeks after completion of RT
Assessment of Toxicity of Treatment Lasso di tempo: Baseline	Evaluate Toxicity of Treatment using Common Terminology Criteria for Adverse Events (CTCAE V.5)	Baseline
Assessment of Toxicity of Treatment Lasso di tempo: Baseline	Assessment of treatment-related toxicity according to health-related quality of life using the EQ-5D questionnaire	Baseline

Misure di risultato secondarie

Misura del risultato	Misura Descrizione	Lasso di tempo
Assess the Time to local disease progression Lasso di tempo: From treatment initiation until the end of the follow up ( 12 months follow up )	Time from the date of treatment initiation to the date of documented local disease progression	From treatment initiation until the end of the follow up ( 12 months follow up )
Assess the Time to EFS Lasso di tempo: From treatment initiation until progression or death	Time from the date of treatment initiation to Event free survival	From treatment initiation until progression or death

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Assiut University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 dicembre 2026

Completamento primario (Stimato)

1 agosto 2027

Completamento dello studio (Stimato)

1 dicembre 2027

Date di iscrizione allo studio

Primo inviato

26 settembre 2026

Primo inviato che soddisfa i criteri di controllo qualità

29 ottobre 2026

Primo Inserito (Effettivo)

3 novembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

3 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

29 ottobre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

Ultrafractionated Radiotherapy

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

prodotto fabbricato ed esportato dagli Stati Uniti

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Sequential Chemotherapy Followed by Ultrahypofractionated Radiotherapy for Muscle-Invasive Bladder Cancer