Prognostic Significance of the Albumin-to-globulin Ratio for Advanced Urothelial Carcinoma Treated with Pembrolizumab: A Multicenter Retrospective Study

Abstract

Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.

Comparison of full-dose gemcitabine/cisplatin, dose-reduced gemcitabine/cisplatin, and gemcitabine/carboplatin in real-world patients with advanced urothelial carcinoma

“…Regarding the prognostic factors, poor performance status (ECOG PS ≥ 1) and liver metastasis were shown to be independent predictors of shorter CSS and OS (Tables 3, 4), in this study. These two factors have been reported as critical prognostic factors for patients with aUC [16][17][18], even in the era of immune checkpoint inhibitors [18]. Our results were similar to findings in the previous literature.…”

Improved survival in real‐world patients with advanced urothelial carcinoma: A multicenter propensity score‐matched cohort study comparing a period before the introduction of pembrolizumab (2003–2011) and a more recent period (2016–2020)

“…These two factors have been recognized as strong prognostic markers for aUC, and their utility has been maintained in the pembrolizumab era (note: liver metastasis was previously included in visceral metastasis along with lung and bone metastases, but it has been handled separately in recent years). [1][2][3][4][5][6][7][8][9][10][11][14][15][16][17][18][19][20] Conversely, resection of the primary site was associated with survival in analyses of the entire cohort (Table 2; Table S2) and a subgroup analysis of patients who did not receive pembrolizumab (Table S6), whereas it had no correlation with survival in a subgroup analysis of patients who used pembrolizumab (Table S4). This might be attributable to the functional mechanism of immune checkpoint inhibitors such as pembrolizumab, the responders to which could benefit irrespective of the residual tumor burden, thus negating the cytoreductive effect of resection of the primary site.…”

“…Notably, CSS (25 months) and OS (24 months) among patients in the recent era cohort who received pembrolizumab were more than 2-fold longer than in patients in the earlier era cohort (CSS and OS: 11 months, Figure 3). Since pembrolizumab was launched as a second-line therapy for aUC in 2017, several studies have reported its outcomes in the real-world setting, [14][15][16][17][18][19][20] and all but one study conducted survival analyses from the start of pembrolizumab therapy. [15][16][17][18][19][20] The remaining study, by Narita et al, performed survival analyses from the start of first-line chemotherapy to compare outcomes between pembrolizumab and conventional chemotherapy as later-line therapies for aUC.…”

“…Since pembrolizumab was launched as a second-line therapy for aUC in 2017, several studies have reported its outcomes in the real-world setting, [14][15][16][17][18][19][20] and all but one study conducted survival analyses from the start of pembrolizumab therapy. [15][16][17][18][19][20] The remaining study, by Narita et al, performed survival analyses from the start of first-line chemotherapy to compare outcomes between pembrolizumab and conventional chemotherapy as later-line therapies for aUC. 14 After excluding patients who received first-line chemotherapy alone (n = 69), the researchers compared OS between patients who probability of treatment weighting method.…”

“…The former cohort was collected from seven institutions, and it included 176 patients treated with pembrolizumab between 2018 and 2020 who were reported in our previous articles. 15,16 The latter cohort was collected from five institutions, and it was identical to a cohort analyzed in another previous article by our group. 7 Therefore, we have obtained permission to reuse the previously published material from the publisher (Springer Nature, license number: 5226721033736).…”