Department of Urology, Sapienza University of Rome, Rome, Italy.
Int Urol Nephrol. 2011 Dec;43(4):1047-57. doi: 10.1007/s11255-011-9941-x. Epub 2011 Mar 29.
The management of stage T1 poorly differentiated G3 bladder cancer invading the lamina propria continues to be debated. These tumours are associated with a high risk of recurrence and progression; concomitant carcinoma in situ and/or multifocality are negative prognostic factors. Choosing between a preserving approach such as trans-urethral resection of the bladder (TURB) followed by maintenance bacillus Calmette-Guerin (BCG) and an invasive approach like cystectomy is critical.
Overall, 80 patients underwent TURB and RE-TURB followed by intra-vesical induction treatment with BCG plus maintenance (Group A) while 72 patients underwent immediate radical cystectomy with extended lymphadenectomy (Group B). Patients were divided into 3 subgroups: uni-focal tumours, multi-focal tumours and carcinoma in situ associated lesions. In Group A, time to first recurrence and time to progression were analysed. A comparison was made between Group A and Group B regarding progression-free survival, cancer-specific survival and overall survival with a median follow-up time of 8.3 years.
As far as concerns Group A patients, 42 recurrences (52.5%) were reported in a median time of 10.4 months (range 3-26) and 25 progressions (31.2%) in a median time of 25 months (range 3-68). As far as concerns time to first recurrence and time to progression, both the Kaplan-Meier survival curves obtained are significant and P values are, respectively, 0.0263 and 0.0011. Comparing Groups A and B patients, 25 progressions (31.2%) in a median time of 25 months (range 3-68) and 18 progressions (25%) in a median time of 25.9 months (range 4-72), respectively, were recorded. Regarding overall survival, at 10 years, 24 deaths (42.5%) occurred in a median time of 55.4 months (range 12-94) in Group A and 42 deaths (58.3%) in a median time of 54.9 months (10-100) in Group B. Cancer-specific survival was evaluated in Group A with a total of 18 deaths (22.5%) in a median time of 47.5 months (range 16-78), and in Group B with a total of 16 deaths (22.2%) in a median time of 45.7 months (range 16-88). The progression-free survival Kaplan-Meier curve is not significant, the P value being 0.3801; the overall survival curve is significant with a P value of 0.0487 while the cancer-specific survival curve is not significant with a P value of 0.9762.
In Group A, considering "time to first recurrence", the difference is greater between unifocal lesions and multifocal or Cis-associated lesions. Conversely, for "time to progression", there is a greater difference between unifocal and multifocal tumours and Cis-associated tumours. Looking at "progression-free survival" in Group A and Group B patients, there is no statistically significant difference, like in cancer-specific survival. A statistically significant difference was observed in overall survival being in favour of conservative treatment thus reflecting that conservative treatment is not burdened by all the surgical and post-operative complications of cystectomy.
Although NMIBC invading the lamina propria, stage G3, with or without Cis-associated lesions are burdened both by a high volume of recurrences and progressions, cystectomy could be considered an aggressive approach. New biological markers are now needed which are able to predict the behaviour of the cancer and to guide the decision-making process between conservative or aggressive treatment.
对于侵犯固有层的 T1 期低分化 G3 膀胱癌的处理仍存在争议。这些肿瘤与高复发和进展风险相关；同时存在原位癌和/或多灶性是预后不良的因素。在经尿道膀胱肿瘤切除术（TURB）联合卡介苗（BCG）维持治疗与膀胱切除术等侵袭性治疗之间进行选择至关重要。
总共 80 例患者接受 TURB 和再次 TURB 联合膀胱内诱导治疗 BCG 加维持治疗（A 组），而 72 例患者接受即刻根治性膀胱切除术和扩大淋巴结清扫术（B 组）。患者分为 3 个亚组：单灶性肿瘤、多灶性肿瘤和原位癌相关病变。在 A 组中，分析了首次复发时间和进展时间。比较了 A 组和 B 组之间无进展生存率、癌症特异性生存率和总生存率，中位随访时间为 8.3 年。
就 A 组患者而言，在中位时间 10.4 个月（范围 3-26）内报告了 42 例（52.5%）复发，在中位时间 25 个月（范围 3-68）内报告了 25 例（31.2%）进展。就首次复发时间和进展时间而言，Kaplan-Meier 生存曲线均有显著差异，P 值分别为 0.0263 和 0.0011。比较 A 组和 B 组患者，在中位时间 25 个月（范围 3-68）内记录了 25 例（31.2%）进展，在中位时间 25.9 个月（范围 4-72）内记录了 18 例（25%）进展。关于总生存率，在 A 组中，在中位时间 55.4 个月（范围 12-94）内有 24 例（42.5%）死亡，在中位时间 54.9 个月（范围 10-100）内有 42 例（58.3%）死亡，在 B 组中。在 A 组中，评估了癌症特异性生存率，共有 18 例（22.5%）死亡，中位时间为 47.5 个月（范围 16-78），在 B 组中，共有 16 例（22.2%）死亡，中位时间为 45.7 个月（范围 16-88）。A 组的无进展生存率 Kaplan-Meier 曲线无显著差异，P 值为 0.3801；总生存率曲线有显著差异，P 值为 0.0487，而癌症特异性生存率曲线无显著差异，P 值为 0.9762。
在 A 组中，考虑到“首次复发时间”，单灶性病变和多灶性或 Cis 相关病变之间的差异更大。相反，对于“进展时间”，单灶性肿瘤和多灶性肿瘤与 Cis 相关肿瘤之间的差异更大。观察 A 组和 B 组患者的“无进展生存率”，无统计学显著差异，与癌症特异性生存率相似。在总生存率方面观察到统计学显著差异，有利于保守治疗，这反映了保守治疗不会带来膀胱切除术的所有手术和术后并发症。
尽管侵犯固有层的 T1 期低分化 G3 膀胱癌，伴有或不伴有 Cis 相关病变，均有较高的复发和进展风险，但膀胱切除术可能是一种侵袭性治疗方法。现在需要新的生物标志物，能够预测癌症的行为，并指导在保守或侵袭性治疗之间做出决策。
