T1G3 high-risk NMIBC (non-muscle invasive bladder cancer): conservative treatment versus immediate cystectomy

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.