TY - JOUR
T1 - Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab
AU - Katayama, Satoshi
AU - Iwata, Takehiro
AU - Kawada, Tasushi
AU - Okamoto, Yusuke
AU - Sano, Yuho
AU - Kawago, Yuya
AU - Miyake, Shuji
AU - Moriwake, Takatoshi
AU - Kuinose, Aya
AU - Horikawa, Yuhei
AU - Tsuboi, Kazuma
AU - Tsuboi, Ichiro
AU - Sakaeda, Kazuma
AU - Nakatsuka, Hirokazu
AU - Takamoto, Atsushi
AU - Hirata, Takeshi
AU - Shirasaki, Yoshinori
AU - Yamasaki, Taku
AU - Morinaka, Hirofumi
AU - Nagasaki, Naoya
AU - Hara, Takafumi
AU - Ochi, Akinori
AU - Okumura, Misa
AU - Watanabe, Tomofumi
AU - Sekito, Takanori
AU - Kawano, Kaoru
AU - Horii, Satoshi
AU - Yamanoi, Tomoaki
AU - Nagao, Kentaro
AU - Yoshinaga, Kasumi
AU - Maruyama, Yuki
AU - Tominaga, Yusuke
AU - Sadahira, Takuya
AU - Nishimura, Shingo
AU - Edamura, Kohei
AU - Kobayashi, Tomoko
AU - Kusumi, Norihiro
AU - Kurose, Kyohei
AU - Yamamoto, Yasuo
AU - Sugimoto, Morito
AU - Nakada, Tetsuya
AU - Sasaki, Katsumi
AU - Takenaka, Tadasu
AU - Ebara, Shin
AU - Miyaji, Yoshiyuki
AU - Wada, Koichiro
AU - Kobayashi, Yasuyuki
AU - Araki, Motoo
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/3
Y1 - 2024/3
N2 - Purpose: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. Methods: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. Results: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. Conclusion: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.
AB - Purpose: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. Methods: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. Results: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. Conclusion: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.
KW - Immune checkpoint inhibitor
KW - Pembrolizumab
KW - Survival
KW - Tumor burden
KW - Tumor size
KW - Urothelial carcinoma
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U2 - 10.1016/j.urolonc.2023.11.009
DO - 10.1016/j.urolonc.2023.11.009
M3 - Article
C2 - 38129282
AN - SCOPUS:85180605267
SN - 1078-1439
VL - 42
SP - 70.e11-70.e18
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 3
ER -
