Comparison of the new American Joint Committee on Cancer substratification in node‐negative pT2 urothelial carcinoma of the bladder: analysis of patient outcomes in a contemporary series
Authors: Gakis Georgios , Schilling David , Renninger Markus , Seibold Joerg , Sievert Karl‐Dietrich , Stenzl Arnulf 
Published: September 2010

Study Type – Prognosis (case series) Level of Evidence 4

What’s known on the subject? and What does the study add?

The prognostic value of pathological substratification in lymph node‐negative pT2 urothelial carcinoma of the bladder based on tumour depth has been controversially discussed in recent studies. In 1997, the AJCC and UICC modified the TNM staging system in bladder cancer providing a new substratification in pT2 bladder cancer based on a previous study of Jewett in 1952 reporting a worse prognosis for patients with deep muscle invasion compared to those with superficial muscle invasion. Recently, this prognostic significance has been considered of minor importance compared to significance of lymph node tumor involvement. Thus, many of these studies concluded that future revisions of the TNM staging system should consolidate both substages. However, these studies were hampered by the inclusion of patients with non‐urothelial carcinoma components, unknown number of retrieved lymph nodes, unknown extent of pelvic lymphadenectomy, and inclusion of patients undergoing neoadjuvant chemotherapy.

This study addresses specifically the prognostic significance of pT2 substaging in urothelial cancer in a contemporary, consecutive series of patients treated with radical cystectomy. All patients had pure urothelial cell carcinoma, and underwent an extended lymphadenectomy approach. The number of retrieved lymph nodes was recorded. There was a significant difference in survival in patients with lymph‐node negative pT2a vs. pT2b disease. Therefore, this study supports the prognostic value of the current substratification in pT2 urothelial carcinoma of the bladder.

OBJECTIVE

• To determine whether there is a difference in survival in patients with node‐negative pT2a vs pT2b urothelial carcinoma of the bladder (UBC), as recent studies suggest that the new American Joint Committee on Cancer substratification may not have prognostic significance.

PATIENTS AND METHODS

• Of 252 patients undergoing radical cystectomy (RC) and extended bilateral pelvic lymphadenectomy (ePLND) between 1999 and 2009, 72 (28.6%), with a mean (range) age of 66 (44–83) years (50 men, 22 women), had pathologically confirmed pT2 UCB.

• Fisher’s exact test and Cox regression analysis were used for uni‐ and multivariate analysis of risk factors of recurrence at a median (range) follow‐up of 28 (2.2–115.7) months.

• Kaplan–Meier plots were used to estimate the impact of pT2 substratification in lymph node (LN)‐negative disease on recurrence‐free (RFS) and cancer‐specific (CSS) survival using log‐rank test.

RESULTS

• Of the 72 patients, 39 had pT2a (54.2%) and 33 pT2b UCB (45.8%) on definitive histological examination. The median (range) number of LNs removed was 19 (6–38) in pT2a and 22 (4–36) in pT2b (P = 0.31) UCB.

• At RC, there was LN‐positive disease in one patient with pT2a UCB, whereas seven patients with pT2b UCB had LN‐positive disease (P = 0.02).

• The median (range) number of LNs removed in LN‐positive disease was 18 (11–30) and in LN‐negative disease was 20 (4–38) (P = 0.52).

• In LN‐negative disease, actuarial 5‐year RFS was 85.9% in patients with pT2a UCB vs 37.5% in those with pT2b UCB (P < 0.001). Actuarial 5‐year CSS was 84.8% in patients with LN‐negative pT2a UCB vs 59.6% in patients with LN‐negative pT2b UCB (P = 0.01).

• In Cox regression analysis, pT2 substratification was the only independent risk factor of recurrence and cancer‐specific death (P < 0.001 and P = 0.008).

CONCLUSIONS

• In this contemporary series of patients undergoing RC with ePLND, there was a significant difference in RFS and CSS between LN‐negative pT2a and pT2b UCB, and pT2 substratification was the only risk factor of recurrence and cancer‐specific death.

• These data are supportive of the current concept of substratification in LN‐negative pT2 UCB.