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. 2021 Nov;206(5):1258-1267.
doi: 10.1097/JU.0000000000001943. Epub 2021 Jun 29.

Progression of Disease after Bacillus Calmette-Guérin Therapy: Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy

Patrick J Hensley  1 , Kelly K Bree  1 , Matthew T Campbell  2 , Omar Alhalabi  2 , Andrea Kokorovic  1 , Tanner Miest  1 , Graciela M Nogueras-Gonzalez  3 , Jianjun Gao  2 , Arlene O Siefker-Radtke  2 , Charles C Guo  4 , Neema Navai  1 , Colin P Dinney  1 , Ashish M Kamat  1
Affiliations

Progression of Disease after Bacillus Calmette-Guérin Therapy: Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy

Patrick J Hensley et al. J Urol. 2021 Nov.

Abstract

Purpose: Data from the pre-neoadjuvant chemotherapy (NAC) era suggests patients who progress on bacillus Calmette-Guérin (BCG) to muscle-invasive bladder cancer (P-MIBC) exhibit worse outcomes compared to de novo MIBC (D-MIBC). Herein, we investigate whether P-MIBC is an independent poor risk factor in the setting of contemporary NAC use.

Materials and methods: A review of patients who underwent radical cystectomy (RC) for cT2-3 MIBC from 2005 to 2018 was performed. Patients were stratified into high risk (lymphovascular invasion, variant histology, hydronephrosis, cT3b) vs low risk (no risk factors) and P-MIBC (≤pT1 treated with at least induction BCG who progressed to ≥cT2) vs D-MIBC.

Results: Among 801 patients who underwent RC 20.3% had P-MIBC and 79.7% had D-MIBC. In low-risk patients treated without NAC, P-MIBC was associated with pathological upstaging (64.9% vs 42.7%, p=0.004) and worse overall (OS, p=0.006) and cancer-specific survival (CSS, p=0.001) compared to D-MIBC. P-MIBC status conferred uniformly poor survival outcomes to patients who did not receive NAC compared to D-MIBC without NAC (median OS 51.5 months [95% CI 40.0-81.0] vs 85.1 months [95% CI 62.8-96.0], p=0.040; median CSS not reached, p=0.014). However, P-MIBC status did not remain a negative prognostic factor in the setting of NAC (median OS 90.5 months [95% CI 34.0-not estimable] vs 87.8 months [95% CI 68.7-not estimable], p=0.606; median CSS not reached, p=0.448).

Conclusions: P-MIBC confers a poor prognosis when managed with RC alone. Treatment with NAC results in equivalent pathological response and survival outcomes compared to D-MIBC. P-MIBC should be included in risk-stratified approaches to NAC selection.

Keywords: cystectomy; mycobacterium bovis; neoadjuvant therapy; urinary bladder neoplasms.

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Figures

Figure 1:
Figure 1:
Pathologic response stratified by MDACC risk criteria and P-MIBC vs. D-MIBC. Risk factors include LVI, variant histology, hydronephrosis, palpable tumors or cT3 disease. (A) Final pathologic outcomes for low-risk (LR; no risk factors) P-MIBC and D-MIBC patients. (B-D) Final pathologic outcomes for high-risk (HR; any risk-factor[s]) stratified by receipt of NAC.
Figure 2.
Figure 2.
Kaplan-Meier survival analysis for (A) overall survival, (B) bladder cancer-specific survival, and (C) recurrence or metastasis-free survival.
Figure 2.
Figure 2.
Kaplan-Meier survival analysis for (A) overall survival, (B) bladder cancer-specific survival, and (C) recurrence or metastasis-free survival.
See this image and copyright information in PMC

Comment in

  • Editorial Comment.
    Barlow LJ, Steinberg GD. Barlow LJ, et al. J Urol. 2021 Nov;206(5):1266-1267. doi: 10.1097/JU.0000000000001943.01. Epub 2021 Aug 10. J Urol. 2021. PMID: 34372684 No abstract available.

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