Adaptive Dose Escalation in Muscle Invasive Bladder Carcinoma (MIBC) – Impact on Organ Preservation and Clinical Outcomes

Abstract

<h3>Purpose/Objective(s)</h3> Carcinoma urinary bladder is mainly a malignancy of elderly with median age at presentation of 65-70 years. Though Radical cystectomy remains the mainstay of management, it is not possible in a subset of patients owing to age, co-morbidities, and psychological/social factors where patient denies surgery. In such scenarios, organ preservation has been tried with a multimodality approach including maximal Transurethral resection of bladder tumor (TURBT), chemotherapy and radiotherapy. However, no standard has been established till date. Here in our study, we attempted adaptive dose escalation using SBRT in patients who received concurrent chemoradiation and analyzed the clinical outcomes associated with it. <h3>Materials/Methods</h3> 13 male patients with histopathologically confirmed MIBC who were considered otherwise inoperable, were prospectively analyzed. All patients underwent maximal TURBT followed by CTRT. Radiotherapy was initially delivered using conventional fractionation and PETCT based planning using Image guided Radiotherapy to a dose of 50-60Gy in 25-28 fractions to the whole bladder and pelvic lymph nodes with concurrent chemotherapy. Later patients were planned for SBRT boost to the residual disease (contoured on PET and MR scans done 7 to 10 days post EBRT) with a dose of 10-21Gy in 2-3 fractions achieving a cumulative BED of 80-100Gy. Gold fiducials were placed in the bladder for real time tumor tracking during treatment. <h3>Results</h3> Median age at presentation was 67 years. Majority of the patients (69%) belong to stage III. Neoadjuvant chemotherapy was given in 23% of patients. After a medial follow-up of 29 months, Overall survival (OS) at the end of 1 year, 2 year and 3 years was 77%, 70% and 54% respectively. Median overall survival was 40 months (range- 7 to 91months) 8% of patients recurred locally and 23% had distant metastasis. 92% (12 patients) had functional organ preservation with low toxicity profile. One patient had grade3/4 genitourinary toxicities post radiation. <h3>Conclusion</h3> Dose escalation using SBRT boost following chemoradiation is a clinically feasible approach for organ preservation in muscle invasive bladder cancer with good oncological outcomes and low rates of acute/late toxicities. With adaptive technique and real time tracking, dose escalation can be considered safe and improve the chances of bladder preservation. However larger sample size is required for validation.