The current classification recommends the reporting of the extent of invasion of T1-BCs. However, the system for sub-staging to be used remains optional. T1 sub-stage based on MM invasion was identified as an important prognostic factor for T1-BC. The T1 sub-staging system may help categorize patients into different subgroups with different clinical outcomes. The typical symptom of MM invasion is the change of MM distribution pattern from a continuous layer to a dispersed smooth muscle cell bundle. It was reported that the presence of MM could be found only in 32% of TURBT specimens, and 17% of biopsy specimens(43–47). In some areas of the bladder, such as trigone, the MM may be difficult to be identified(48), while the rate of MM discovery has increased up to 100% in more recent reports now. Most of them agreed on a 90% discovery rate(15). It is important for urologists and pathologists to work together to identify the MM invasion. Firstly, the urologists need to minimize the cautery injury when performing TURBT, and submit the tumor base separately. These will enable the pathologist to have a better opportunity to identify the MM invasion depth. En-bloc resection using monopolar or bipolar current, Thulium-YAG or Holmium-YAG laser is proven to be feasible. It provides resected specimens of high quality with detrusor muscle preserved(49, 50). Secondly, well trained pathologists need to sub-stage the tumor in most patients with stage T1-BC.
Martin-Doyle et al(3) previously conducted a meta-analysis in comparing the recurrence rate between T1a and T1b/c high-grade BC based on six studies published before 2015. They found that T1a high-grade BC patients had no difference in recurrence compared with T1b/c high-grade BC patients (HR, 1.29; 95% CI, 0.93–1.78; P = 0.127). We evaluated 20 studies including both T1 low-grade BC and T1 high-grade BC. We found the difference in recurrence between T1a BC and T1b BC patients (HR, 1.28; 95%CI, 1.14–1.43 ). The different clinical outcomes in our study was explained as follows: Firstly, the population in our study covered all types of T1-BC, rather than T1 high-grade BC. Secondly, most studies focused on progression rate, with fewer studies reporting the recurrence of BC. Thirdly, the invasion of MM was more frequently discovered.
We analyzed the heterogeneity in studies, which evaluated RFS and CSS with meta-regression. As individual patient data were not accessible, the assessment of heterogeneity was limited. We only analyzed the factors of publication year and race using covariate meta-regression respectively. We found the publication year was related to the heterogeneity in studies which evaluated PFS (P = 0.014), while the race was not related to the heterogeneity (p = 0.822). We found that neither publication year (p = 0.538) nor race (P = 0.705) was related to the heterogeneity in studies which evaluated CSS. Although we identified little evidence of publication bias, we might have limited capabilities to detect the bias, given the limitations of available techniques(51). This publication bias might be originated from selective reporting of results.
The treatment of T1-BC remains controversial. For patients receiving no adjuvant intravesical treatment, the progression rate was 9.1% in patients with T1a tumor, whereas it was 50% in patients with T1b tumor (11). Orsola et al (15) reported that in BCG-treated patients, the progression rate was 8% in patients with T1a tumor, whereas it was 34% in patients with T1b tumor. Overall the progression rate of T1b patients was higher than that of T1a patients. In our study, T1b patients had worse RFS, PFS and CSS than T1a patients. So patients with T1a tumor could be managed conservatively with TURBT and intravesical BCG treatment. But patients with T1b tumor should be recommended to receive more aggressive treatment.
There were some limitations in our study. Firstly, all included studies were retrospective observational studies with selection biases. Secondly, insufficient data which lacked details on presence of carcinoma in situ and employment of whether re-TURBT or intravesical treatment, limited further analyses. Thirdly, we did not distinguish between low grade and high grade cancers, which might also influence disease recurrence and progression.