addition, disease-free survival was 72.7% in. T2 patients and 27.3% in T3 patients (P = 0.001). CONCLUSION. ⢠In the present study, bladder preservation.
2010 THE AUTHORS. JOURNAL COMPILATION Urological Oncology
2010 BJU INTERNATIONAL
BLADDER PRESERVATION MULTIMODALITY THERAPY MAAROUF ET AL.
BJUI
Bladder preservation multimodality therapy as an alternative to radical cystectomy for treatment of muscle invasive bladder cancer
BJU INTERNATIONAL
Aref M. Maarouf, Salem Khalil, Emad A. Salem, Mahmoud ElAdl, Nashwa Nawar* and Fatma Zaiton** Departments of Urology, *Radiotherapy and Radiology, **Faculty of Medicine, Zagazig University, Zagazig, Egypt Accepted for publication 25 May 2010
Study Type – Therapy (case series) Level of Evidence 4
OBJECTIVE • To evaluate the efficacy of a bladder preservation multimodality protocol for patients with operable carcinoma invading bladder muscle.
What’s known on the subject? and What does the study add? The subject of bladder preservation multimodality protocols in muscle invasive bladder TCC is not new. In our study, even in a highly selected group of patients, multimodality protocol with M-VAC and radiation therapy achieved suboptimal results at 1 year. This emphasized the role of radical cystectomy as the gold standard treatment for invasive bladder TCC. tomography and chest X-ray were conducted every 6 months. • The study endpoint was the response to treatment after completion of the first year of follow-up after therapy.
MATERIALS AND METHODS RESULTS • In this prospective study, we included 33 patients with transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to complete transurethral resection. • These patients refused radical cystectomy as their first treatment option. After maximum transurethral resection of bladder tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by radical radiotherapy. • Four weeks later, all cases had radiological and cystoscopical re-evaluation. • Complete responders were considered to be those patients who had no evidence of residual tumour. All patients were subjected to a regular follow-up by cystoscopy and tumour site biopsy conducted every 3 months. Abdomino-pelvic computed
INTRODUCTION At present, radical cystectomy represents the treatment of choice for patients with urothelial carcinoma invading bladder muscle, achieving a 5-year disease-specific
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• Out of 33 eligible patients, a total of 28 patients completed the study treatment protocol. Their mean ± SD age was 56.7 ± 6 years. Trimodal therapy was well tolerated in most of cases, with no severe acute toxicities. After 12 months of follow-up, a complete response was achieved in 39.3% and a partial response in 7.1%, with an overall response rate of 46.4%. • By the end of the first year, disease-free survival was reported in 39.3%, whereas 25% were still alive with their disease, giving an overall survival of 64.3% for all patients who maintained their intact, well functioning bladders. • Tumour stage and completeness of transurethral resection of bladder tumour were the most important predictors of response and survival. T2 lesions had complete and partial response rates of
survival rate of 68% [1]. In patients with organ confined disease, a 5-year recurrencefree survival of 73% [2] and 75% [3], was obtained. However, radical cystectomy is associated with significant morbidity rate of ≈30%, even in experienced centres [4].
69.2% and 23%, respectively, whereas T3 lesions had rates of 40% and 13.3%, respectively (P = 0.001). • The response rate in patients who had complete TURBT was 82.6% vs 20% in those with cystoscopic biopsy only (P = 0.001). In addition, disease-free survival was 72.7% in T2 patients and 27.3% in T3 patients (P = 0.001). CONCLUSION • In the present study, bladder preservation protocol with MVAC and radical radiotherapy achieved suboptimal response rates at 1 year in patients with localized TCC invading bladder muscle. Patients with solitary T2 lesions that are amenable to complete TURBT achieved the best response rates. Longer follow-up is needed to verify these results. Patients with localized disease should be encouraged for radical cystectomy, which achieved better results. KEYWORDS bladder preservation, multimodality therapy, muscle invasive bladder cancer
Additionally, the functional results regarding continence and sexuality still represent a major concern for patients, despite the application of nerve-sparing procedures and continent urinary diversions [5,6].
2010 THE AUTHORS
BJU INTERNATIONAL
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2 0 1 0 B J U I N T E R N A T I O N A L | 1 0 7 , 1 6 0 5 – 1 6 1 0 | doi:10.1111/j.1464-410X.2010.09564.x
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Bladder preservation emerged as a necessity for patients deemed medically unfit for surgery, although it has subsequently been considered for other patients as well, aiming to preserve natural voiding and sexual function, both of which are fundamental components of health-related quality of life [7]. Complete transurethral resection of the bladder tumour (TURBT) has been proposed as a method to remove all of the malignant tissues without interfering with the normal lower urinary tract. Nevertheless, this procedure could be justified as a monotherapy only when the tumour is limited to the superficial muscle layer [8–11]. With disease invading muscle, many organpreservation strategies combine TURBT, chemotherapy and radiation, aiming to give the patient the best chance of controlling the disease, in addition to keeping the bladder [12–17]. The rationale for performing TURBT and radiation is to achieve local tumour control. Application of systemic chemotherapy, most often in the form of methrotrexate, cisplatin and vinblastine, aims to eradicate micrometastasis [18]. In selected patients, single-modality or multimodality bladder preservation protocols have been associated with a considerable disease-free survival [7,16].
treatment option. Patients were required to provide their written informed consent, including the possibility of salvage cystectomy in cases of treatment failure.
diagnosis or those with residual muscle invasive disease at second TURBT.
Additional eligibility criteria included an absence of hydronephrosis; either no involvement of prostatic urethra or involvement limited to its mucosa, with no evidence of stromal invasion; an adequately functioning bladder, haemoglobin ≥10 mg/dL, white blood count ≥4000 per mL, absolute neutrophil count ≥1800 per mL, platelet count ≥100 000 mm3 and creatinine clearance ≥60 mL/min. Patients were required to have a performance score ≥2 according to the Eastern Cooperative Oncology Group. Thirty-three patients met the eligibility criteria for the study.
Patients were planned to receive three cycles of MVAC chemotherapy, 2–3 weeks after the tumour resection, to allow the opportunity for adequate healing. The schedule was: methotrexate, 30 mg/m2 i.v. on days 1, 15 and 22; vinblastin 3 mg/m2 i.v. on days 2, 15 and 22; adriamycin 30 mg/m2 i.v. on day 2; and cisplatin 70 mg/m2 infusion on day 2.
In all patients, TURBT was carried out with the aim of tissue diagnosis, staging and maximal excision of the lesion. All patients underwent contrast-enhanced abdomino-pelvic CT, chest X-ray and chest CT when clinically indicated to exclude chest metastasis, as well as complete blood count, liver and kidney function, urine analysis, urine culture and sensitivity tests. Echocardiography with measurement of ejection fraction had also to be done. It was required that patients could be considered as suitable candidates for radical cystectomy. EXCLUSION CRITERIA
In the present study, we evaluated multimodality bladder preservation strategy combining TURBT, radiotherapy and chemotherapy for the treatment of patients with operable carcinoma invading bladder muscle.
Exclusion criteria included an Eastern Cooperative Oncology Group performance status
