不可手术局部浸润性膀胱癌保膀胱综合治疗疗效分析

The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis

目的评价局限于盆腔的浸润性膀胱癌保膀胱综合治疗的疗效及不良反应,探讨预后影响因素。方法1999年3月至2021年12月在中国医学科学院肿瘤医院接受保膀胱综合治疗的浸润性膀胱癌患者69例,均接受放疗,其中42例接受同步化疗,32例接受新辅助化疗,43例放疗前接受过经尿道膀胱肿瘤电切术。随访观察患者的晚期放疗不良反应、膀胱功能、肿瘤复发转移和生存情况,采用Cox模型进行预后影响因素的多因素分析。结果69例患者的中位年龄为69岁,其中尿路上皮癌63例;Ⅲ期64例,Ⅳ期4例。中位随访76个月,晚期泌尿道反应2级7例,消化道反应2级2例,无3级及以上不良反应发生。除8例因膀胱内肿瘤未控失去膀胱功能外,其余患者均保持了正常膀胱功能。局部复发17例。同步放化疗组11例,局部复发率为26.2%(11/42),非同步放化疗组6例,局部复发率为22.2%(6/27),两组局部复发率差异无统计学意义(P=0.709)。远处转移23例(包括2例局部复发伴远转),其中同步放化疗组10例,远处转移率为23.8%(10/42),非同步放化疗组13例,远处转移率为48.1%(13/27),非同步放化疗组的远处转移率高于同步放化疗组(P=0.036)。69例患者的中位总生存时间为59个月,5年总生存率为47.8%;中位无进展生存时间为20个月,5年无进展生存率为34.4%。同步放化疗和非同步放化疗患者的5年总生存率分别为62.9%和27.6%(P<0.001),5年无进展生存率分别为45.4%和20.0%((P=0.022)。有无新辅助化疗患者的5年总生存率分别为78.4%和30.1%(P=0.002),5年无进展生存率分别为49.1%和25.1%(P=0.087)。放疗前有无局部电切患者的5年总生存率分别为45.5%和51.9%(P=0.233),5年无进展生存率分别为30.8%和39.9%(P=0.198)。多因素Cox回归分析显示,临床分期(HR=0.422,95%CI:0.205~0.869)是浸润性膀胱癌患者无进展生存的独立影响因素,临床分期(HR=0.278,95%CI:0.114~0.678)、同步化疗(HR=0.391,95%CI:0.165~0.930)、新辅助化疗(HR=0.188,95%CI:0.058~0.611)、复发(HR=10.855,95%CI:3.655~32.238)是浸润性膀胱癌患者总生存的独立影响因素。结论不可手术局部浸润性膀胱癌通过放疗为主的保膀胱综合治疗可取得满意的远期疗效,大部分患者可保留正常膀胱功能,晚期不良反应可接受,其中早期、同步放化疗、新辅助化疗的患者改善生存尤为明显。

Objective Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done,also including the bladder function preservation and adverse effects analysis.Methods Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected.Among them,42 patients received concurrent chemoradiotherapy,32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors(TURBT)prior to radiotherapy.The late adverse effect of radiotherapy,preservation of bladder function,replase and metastasis and survival were followed-up.Cox proportional hazards models were applied for the multifactorial analysis.Results The median age was 69 years.There were 63 cases(91.3%)of uroepithelial carcinoma,64 of stageⅢand 4 of stageⅣ.The median duration of follow-up was 76 months.There were 7 grade 2 late genito urinary toxicities,2 grade 2 gastrointestinal toxicities,no grade 3 or higher adverse events occurred.All patients maintained normal bladder function,except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder.Seventeen cases recurred locally.There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2%(11/42)and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2%(6/27),and the difference in local recurrence rate between the two groups was not statistically significant(P=0.709).There were 23 cases of distant metastasis(including 2 cases of local recurrence with distant metastasis),including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8%(10/42)and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1%(13/27),and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group(P=0.036).The median 5-year overall survival(OS)time was 59 months and the OS rate was 47.8%.The 5-year progression-free survival(PFS)time was 20 months and the PFS rate was 34.4%.The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9%and 27.6%(P<0.001),and 5-year PFS rates were 45.4%and 20.0%,respectively(P=0.022).The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4%and 30.1%(P=0.002),and the 5-year PFS rates were 49.1%and 25.1%(P=0.087),respectively.The 5-year OS rates with or without TURBT before radiotherapy were 45.5%and 51.9%(P=0.233)and the 5-year PFS rates were 30.8%and 39.9%(P=0.198),respectively.Multivariate Cox regression analysis results showed that the clinical stage(HR=0.422,95%CI:0.205-0.869)was independent prognostic factor for PFS of invasive bladder cancer.The multivariate analysis showed that clinical stages(HR=0.278,95%CI:0.114-0.678),concurrent chemoradiotherapy(HR=0.391,95%CI:0.165-0.930),neoadjuvant chemotherapy(HR=0.188,95%CI:0.058-0.611),and recurrences(HR=10.855,95%CI:3.655-32.638)were independent prognostic factors for OS of invasive bladder cancer.Conclusion Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy,most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early,concurrent chemoradiotherapy and neoadjuvant chemotherapy.