Department of Radiotherapy-Oncology, Ghent University Hospital, Ghent, Belgium.
Department of Radiation-Oncology, Iridium Network, Antwerp, Belgium.
Eur Urol Focus. 2022 Sep;8(5):1238-1245. doi: 10.1016/j.euf.2021.11.004. Epub 2021 Dec 8.
High-risk muscle-invasive bladder cancer (MIBC) has a poor prognosis. Old trials showed that external beam radiotherapy (EBRT) after radical cystectomy (RC) decreases the incidence of local recurrences but induces severe toxicity.
To evaluate the toxicity and local control rate after adjuvant EBRT after RC delivered with volumetric arc radiotherapy.
DESIGN, SETTING, AND PARTICIPANTS: This is a multicentric phase 2 trial. From August 2014 till October 2020, we treated 72 high-risk MIBC patients with adjuvant EBRT after RC. High-risk MIBC is defined as ≥pT3-MIBC ± lymphovascular invasion, fewer than ten lymph nodes removed, pathological positive lymph nodes, or positive surgical margins.
Patients received 50 Gy in 25 fractions with intensity-modulated radiotherapy to the pelvic lymph nodes ± cystectomy bed.
The primary outcome is acute toxicity. We report on local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS), and bladder cancer-specific survival (BCSS).
The median follow-up is 18 mo. Forty-two patients (61%) developed acute grade 2 gastrointestinal (GI) toxicity. Four patients (6%) had acute grade 3 GI toxicity. One patient had grade 5 diarrhea and vomiting due to obstruction at 1 mo. Two-year probabilities of developing grade ≥3 and ≥2 GI toxicity were 17% and 76%, respectively. Urinary toxicity, assessed in 17 patients with a neobladder, was acceptable with acute grade 2 and 3 urinary toxicity reported in 53% (N = 9) and 18% (N = 3) of the patients, respectively. The 2-yr LRFR is 83% ± 5% and the 2-yr CRFS rate is 43% with a median CRFS time of 12 mo (95% confidence interval: 3-21 mo). Two-year OS and BCSS are 52% ± 7% and 62% ± 7%, respectively. Shortcomings are the nonrandomized study design and limited follow-up.
Adjuvant EBRT after RC can be administered without excessive severe toxicity.
In this report, we looked at the incidence of toxicity and local control after adjuvant external beam radiotherapy (EBRT) following radical cystectomy (RC) in high-risk muscle-invasive bladder cancer patients. We found that adjuvant EBRT was feasible and resulted in good local control. We conclude that these data support further enrollment of patients in ongoing trials to evaluate the place of adjuvant EBRT after RC.
高危肌层浸润性膀胱癌（MIBC）预后较差。既往研究表明，根治性膀胱切除术（RC）后行外照射放疗（EBRT）可降低局部复发率，但会引起严重的毒性。
评估容积弧形调强放疗后 RC 术后辅助 EBRT 的毒性和局部控制率。
设计、地点和参与者：这是一项多中心 2 期临床试验。自 2014 年 8 月至 2020 年 10 月，我们对 72 例高危 MIBC 患者采用 RC 术后辅助 EBRT 进行治疗。高危 MIBC 定义为≥pT3-MIBC±脉管浸润、淋巴结清扫数＜10 枚、病理阳性淋巴结或阳性切缘。
患者接受盆腔淋巴结±膀胱切除术床的调强放疗 50 Gy，共 25 次。
主要结局是急性毒性。我们报告局部无复发生存率（LRFR）、临床无复发生存率（CRFS）、总生存率（OS）和膀胱癌特异性生存率（BCSS）。
中位随访时间为 18 个月。42 例（61%）患者发生急性 2 级胃肠道（GI）毒性。4 例（6%）患者发生急性 3 级 GI 毒性。1 例患者在 1 个月时因梗阻出现 5 级腹泻和呕吐。2 年时发生≥3 级和≥2 级 GI 毒性的概率分别为 17%和 76%。17 例接受新膀胱手术的患者评估了尿毒性，急性 2 级和 3 级尿毒性的报告率分别为 53%（N=9）和 18%（N=3），尿毒性是可以接受的。2 年 LRFR 为 83%±5%，2 年 CRFS 率为 43%，CRFS 中位时间为 12 个月（95%置信区间：3-21 个月）。2 年 OS 和 BCSS 分别为 52%±7%和 62%±7%。局限性在于非随机研究设计和随访时间有限。
RC 后辅助 EBRT 可在不引起严重毒性的情况下进行。
在本报告中，我们观察了高危肌层浸润性膀胱癌患者根治性膀胱切除术后辅助外照射放疗（EBRT）后的毒性和局部控制情况。我们发现辅助 EBRT 是可行的，并且具有良好的局部控制效果。我们得出结论，这些数据支持在正在进行的试验中进一步招募患者，以评估 RC 术后辅助 EBRT 的地位。
