Department of Urology, ASST Papa Giovanni XXIII, Bergamo, Italy.
Department of Urology, ASST Papa Giovanni XXIII, Bergamo, Italy.
Urol Oncol. 2022 Feb;40(2):61.e9-61.e19. doi: 10.1016/j.urolonc.2021.07.009. Epub 2021 Jul 29.
The presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants.
We evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage.
Median age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease). Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomy Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants.
Concomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.
经尿道切除术中存在原位癌已知会增加复发和进展为侵袭性疾病的风险。然而，由于膀胱癌行根治性膀胱切除术时同时存在原位癌的预后作用的证据存在争议。此外，同时存在原位癌与膀胱组织学变异显著相关。我们研究的目的是评估在纯尿路上皮膀胱癌中，与组织学变异相比，根治性膀胱切除术中同时存在原位癌是否会影响复发和生存结果。
我们评估了 2009 年 1 月至 2019 年 5 月在一家三级转诊中心接受根治性膀胱切除术治疗的 410 例非转移性膀胱癌患者。根据原位癌的存在对患者进行分层。采用 Kaplan-Meier 方法比较纯尿路上皮和组织学变异膀胱癌患者的无复发生存、癌症特异性生存和总体生存。根据病理分期，Cox 比例风险回归分析模型用于预测纯尿路上皮和组织学变异膀胱癌患者的复发、癌症特异性和总体死亡率。
中位年龄为 71 岁。340 名（82%）患者为男性。中位随访 32 个月时，疾病复发、癌症特异性死亡率和总体死亡率分别为 37%（155 例）、32.9%（135 例）和 46.6%（191 例）。根治性膀胱切除术中同时存在和单纯原位癌的比例分别为 39%和 19%。与纯尿路上皮膀胱癌（35.4%）相比，组织学变异患者中同时存在原位癌更为常见（50.9%）（P 值<.001），且与更差的病理特征相关（血管淋巴管侵犯、淋巴结受累和非器官局限疾病）。在 Kaplan-Meier 分析中，无复发生存率在单纯原位癌患者中显著高于同时存在或无原位癌患者（均 P<.001），在根治性膀胱切除术中无原位癌患者也显著高于同时存在 Cis 患者（P=.02）。与同时存在或无原位癌患者相比，单纯原位癌患者的癌症特异性和总体生存率均显著提高（均 P<.001）。相反，在根治性膀胱切除术中，无原位癌患者与同时存在原位癌患者之间无显著差异（P>0.1）。此外，在组织学变异中，根治性膀胱切除术中同时存在原位癌与更高的无复发生存率相关。多变量 Cox 比例风险回归分析显示，在总体人群和根据组织学分层的患者中，根治性膀胱切除术中存在原位癌与任何生存效果或复发无关（均 P>.05）。然而，在患有尿路上皮膀胱癌和组织学变异的器官局限性疾病患者亚组中，同时存在原位癌是复发的独立预测因子。
根治性膀胱切除术后同时存在原位癌应被视为膀胱癌侵袭性的代表。基于其预后意义，同时存在原位癌应在器官局限性疾病患者中进行严格随访，这些患者可能需要辅助治疗，无论是在纯尿路上皮膀胱癌还是组织学变异中。
