Impact of Performance Status on Oncologic Outcomes in Patients with Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitor: A Systematic Review and Meta-analysis

TY - JOUR

T1 - Impact of Performance Status on Oncologic Outcomes in Patients with Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitor: A Systematic Review and Meta-analysis

AU - Kawada, Tatsushi

AU - Yanagisawa, Takafumi

AU - Mostafaei, Hadi

AU - Sari Motlagh, Reza

AU - Quhal, Fahad

AU - Rajwa, Pawel

AU - Laukhtina, Ekaterina

AU - von Deimling, Markus

AU - Bianchi, Alberto

AU - Majdoub, Muhammad

AU - Pallauf, Maximilian

AU - Pradere, Benjamin

AU - Teoh, Jeremy Yuen-Chun

AU - Karakiewicz, Pierre I

AU - Araki, Motoo

AU - Shariat, Shahrokh F

PY - 2023/3

Y1 - 2023/3

N2 - ContextImmune checkpoint inhibitors (ICIs) are widely used in the management of patients with advanced urothelial carcinoma (aUC). However, its performance in aUC patients with poor performance status (PS) remains unknown.ObjectiveWe aimed to assess the impact of patients’ performance status on the oncologic outcomes in patients with aUC treated with ICIs.Evidence acquisitionWe searched PubMed, Web of Science, and Scopus from inception until July 2022 to identify studies assessing the association between the Eastern Cooperative Oncology Group (ECOG) PS and the oncologic outcomes in patients with aUC treated with ICIs in randomised (RCTs) and nonrandomised (NRCTs) control studies according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The outcomes of our interests were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rate (ORR).Evidence synthesisOverall, six RCTs comprising 5428 patients and 32 NRCTs comprising 6069 patients were included. The meta-analysis of the RCTs revealed that patients with ECOG PS = 0 and PS ≥1 had a trend towards better OS with ICIs compared with those treated with chemotherapy (pooled hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.71–1.04, and HR: 0.74, 95% CI: 0.53–1.03, respectively). There was no significant difference in terms of response to ICIs between patients with poor and good PS (I2 = 0%, p = 0.46). The meta-analysis of the NRCTs revealed that patients with PS ≥2 had significantly worse OS than those with PS <2 (pooled HR: 2.52, 95% CI: 2.00–3.17), as well as worse CSS (pooled HR: 3.35, 95% CI: 1.90–5.91), PFS (pooled HR: 2.89, 95% CI: 1.67–5.01), and ORR (pooled odds ratio: 0.47, 95% CI: 0.27–0.82). Similarly, patients with PS ≥1 had significantly worse oncologic outcomes than those with PS = 0.ConclusionsIn the NRCTs, poor PS was correlated with worse oncologic outcomes in aUC patients treated with ICIs. In the RCTs, ICIs performed better than chemotherapy across all PS categories. These findings should be interpreted with caution due to the high heterogeneity across the studies and patient populations. More RCTs including poor PS are needed to assess the impact of PS on ICI therapy outcomes.Patient summaryImmune therapy for patients with urothelial carcinoma should not be restricted on the grounds of performance status. However, patients with poor performance status should be considered for other factors such as life expectancy and comorbidities.

AB - ContextImmune checkpoint inhibitors (ICIs) are widely used in the management of patients with advanced urothelial carcinoma (aUC). However, its performance in aUC patients with poor performance status (PS) remains unknown.ObjectiveWe aimed to assess the impact of patients’ performance status on the oncologic outcomes in patients with aUC treated with ICIs.Evidence acquisitionWe searched PubMed, Web of Science, and Scopus from inception until July 2022 to identify studies assessing the association between the Eastern Cooperative Oncology Group (ECOG) PS and the oncologic outcomes in patients with aUC treated with ICIs in randomised (RCTs) and nonrandomised (NRCTs) control studies according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The outcomes of our interests were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rate (ORR).Evidence synthesisOverall, six RCTs comprising 5428 patients and 32 NRCTs comprising 6069 patients were included. The meta-analysis of the RCTs revealed that patients with ECOG PS = 0 and PS ≥1 had a trend towards better OS with ICIs compared with those treated with chemotherapy (pooled hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.71–1.04, and HR: 0.74, 95% CI: 0.53–1.03, respectively). There was no significant difference in terms of response to ICIs between patients with poor and good PS (I2 = 0%, p = 0.46). The meta-analysis of the NRCTs revealed that patients with PS ≥2 had significantly worse OS than those with PS <2 (pooled HR: 2.52, 95% CI: 2.00–3.17), as well as worse CSS (pooled HR: 3.35, 95% CI: 1.90–5.91), PFS (pooled HR: 2.89, 95% CI: 1.67–5.01), and ORR (pooled odds ratio: 0.47, 95% CI: 0.27–0.82). Similarly, patients with PS ≥1 had significantly worse oncologic outcomes than those with PS = 0.ConclusionsIn the NRCTs, poor PS was correlated with worse oncologic outcomes in aUC patients treated with ICIs. In the RCTs, ICIs performed better than chemotherapy across all PS categories. These findings should be interpreted with caution due to the high heterogeneity across the studies and patient populations. More RCTs including poor PS are needed to assess the impact of PS on ICI therapy outcomes.Patient summaryImmune therapy for patients with urothelial carcinoma should not be restricted on the grounds of performance status. However, patients with poor performance status should be considered for other factors such as life expectancy and comorbidities.

U2 - 10.1016/j.euf.2023.01.019

DO - 10.1016/j.euf.2023.01.019

M3 - SCORING: Review article

C2 - 36774273

VL - 9

SP - 264

EP - 274

JO - EUR UROL FOCUS

JF - EUR UROL FOCUS

SN - 2405-4569

IS - 2

ER -