Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: a nationwide study of 5417 patients

Abstract

Purpose Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). Methods Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995–December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017–October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with <(y)pT2N0 vs. <(y)pT2N+ disease was estimated by the Kaplan–Meier method. Results In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to <(y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of <(y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with <(y)pT2N+ and <(y)pT2N0, median OS was 3.5 years (95% CI 2.5–8.9) versus 12.9 years (95% CI 11.7–14.0), respectively. Conclusion Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.

A case of neoadjuvant chemotherapy‐resistant muscle‐invasive bladder cancer that markedly responded to pembrolizumab before conversion radical cystectomy

“…Another study reported that 5‐year overall survival of patients with residual cancer (ypT2‐4 or ypN+) after NAC was 21%, whereas that of cases with pCR was 82% 12 . Occult LNM after RC also showed a poor prognosis 13,14 . In the PURE‐01 study of neoadjuvant pembrolizumab, all MIBC patients enrolled in the study underwent RC, and 42% of patients achieved pCR 9 .…”

“… 12 Occult LNM after RC also showed a poor prognosis. 13 , 14 In the PURE‐01 study of neoadjuvant pembrolizumab, all MIBC patients enrolled in the study underwent RC, and 42% of patients achieved pCR. 9 Considering the poor prognosis of ypN+ cases after NAC and RC, systemic immunotherapy with a view to converting RC may increase the possibility of cure.…”

Outcomes and Prognostic Factors of Patients with Urothelial Carcinoma Undergoing Radical Cystectomy and pT0 in the Final Histology Without Neoadjuvant Chemotherapy

“…21,22 The rate of occult lymph node metastases is high (4%) and important to consider when counselling patients, because it directly impacts the survival of patients. 23 Apart from initial tumor stage other local individual patient findings may offer insights on potential outcomes of pT0. We present a comprehensive and contemporary analysis of those findings.…”

The role of surgery for locally advanced urothelial cancers

“…Currently, there is an ongoing randomized control trial comparing a standard pelvic lymphadenectomy to an extended one at the time of radical cystectomy that will help clarify this [11]. However, despite the use of pelvic lymphadenectomy at the time of radical cystectomy, patients with nodal metastases have characteristically diminished overall survival even within the setting of no residual muscle invasive disease on final pathology at the time of radical cystectomy [6 ▪ ,12]. One study showed a median survival of 3.5 years in patients without residual primary tumor but residual nodal involvement at the time of cystectomy compared with 14.1 years in T0N0 bladder cancer [12].…”

“…However, despite the use of pelvic lymphadenectomy at the time of radical cystectomy, patients with nodal metastases have characteristically diminished overall survival even within the setting of no residual muscle invasive disease on final pathology at the time of radical cystectomy [6 ▪ ,12]. One study showed a median survival of 3.5 years in patients without residual primary tumor but residual nodal involvement at the time of cystectomy compared with 14.1 years in T0N0 bladder cancer [12]. Similarly, a study investigating survival outcomes in patients with clinically bulky nodal involvement showed reduced recurrence-free survival in node-positive patients.…”