Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder

• Published in: Urologic oncology 2019-07, Vol.37 (7), p.478-484
• Main Authors: Owyong, Michael, Lotan, Yair, Kapur, Payal, Panwar, Vandana, McKenzie, Tiffani, Lee, Thomas K., Zi, Xiaolin, Martin, Jeremy W., Mosbah, Ahmed, Abol-Enein, Hassan, Ghoneim, Mohamed, Youssef, Ramy F.
• Format: Article
• Language: English
• Subjects: biomarker; bladder cancer; cystectomy; programmed cell death 1 ligand 1 protein; squamous cell carcinoma
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2019.02.017

Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. Median patient age was 52 years (range: 36–74 years) and median length of follow up was 63 months (range: 1–100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06–3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22–6.82, P = 0.02). Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.