Abstract：
Although upper tract urothelial carcinoma (UTUC) is more common in the elderly, outcomes of neoadjuvant chemotherapy (NAC) in this population have never been explored. The objective of the study was to assess the impact of NAC on pathologic response and oncological outcomes stratified by age.
This multicenter study included 164 patients treated with NAC and radical nephroureterectomy (RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based chemotherapies. Pathologic responses were defined as pathologic objective response (pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable logistic and Cox regression analyses were performed to identify predictors for pathologic response and survival outcomes.
The cohorts\' median age was 68 years with the elderly group (> 68 years) comprising 74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%) (P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively, MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific survival, whereas a lower rate was seen in overall survival for the elderly.
Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible patients undergoing non-cisplatin-based NAC appeared to have lower response rates and should be considered for immediate RNU.
This multicenter study included 164 patients treated with NAC and radical nephroureterectomy (RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based chemotherapies. Pathologic responses were defined as pathologic objective response (pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable logistic and Cox regression analyses were performed to identify predictors for pathologic response and survival outcomes.
The cohorts\' median age was 68 years with the elderly group (> 68 years) comprising 74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%) (P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively, MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific survival, whereas a lower rate was seen in overall survival for the elderly.
Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible patients undergoing non-cisplatin-based NAC appeared to have lower response rates and should be considered for immediate RNU.
摘要：
尽管上尿路尿路上皮癌（UTUC）在老年人中更常见，新辅助化疗(NAC)在该人群中的结局从未被研究过.该研究的目的是评估NAC对按年龄分层的病理反应和肿瘤结局的影响。
这项多中心研究包括164例接受NAC和根治性肾输尿管切除术（RNU）治疗的临床非转移性患者，高风险UTUC。根据中位年龄将队列分为两组。患者接受基于顺铂或非顺铂的化疗。病理反应定义为病理客观反应(pOR;≤ypT1N0)和病理完全反应(pCR;ypT0N0)。进行单变量和多变量logistic和Cox回归分析，以确定病理反应和生存结果的预测因子。
队列的中位年龄为68岁，老年组（>68岁）包括74名患者。新辅助化疗包括甲氨蝶呤-长春碱-多柔比星-顺铂（MVAC）66（40％），吉西他滨顺铂（GC）66例（40％），非顺铂化疗32例（20％）。年轻患者接受MVAC的频率更高(50%vs.28%)，而老年人接受更多GC(34%vs.47%）或非顺铂化疗（16%vs.24%）（P=.02）。总的来说,不同年龄段的pOR和pCR相似(52%vs.47%；P=0.5和10%vs.8%；P=.7）。虽然GC和非顺铂化疗显示较低的pCR为5％和3％，分别,MVAC显示pCR为17％（P=0.03），并且与较高的pCR独立相关（OR4.31；P=0.03）。Kaplan-Meier分析显示无复发生存率和癌症特异性生存率无差异。而老年人的总生存率较低。
患有高风险UTUC的老年患者在RNU之前有资格接受基于顺铂的NAC治疗，可能与年轻患者一样受益于这种多模式治疗。顺铂不合格的患者接受非顺铂为基础的NAC似乎有较低的反应率，应考虑立即RNU。
这项多中心研究包括164例接受NAC和根治性肾输尿管切除术（RNU）治疗的临床非转移性患者，高风险UTUC。根据中位年龄将队列分为两组。患者接受基于顺铂或非顺铂的化疗。病理反应定义为病理客观反应(pOR;≤ypT1N0)和病理完全反应(pCR;ypT0N0)。进行单变量和多变量logistic和Cox回归分析，以确定病理反应和生存结果的预测因子。
队列的中位年龄为68岁，老年组（>68岁）包括74名患者。新辅助化疗包括甲氨蝶呤-长春碱-多柔比星-顺铂（MVAC）66（40％），吉西他滨顺铂（GC）66例（40％），非顺铂化疗32例（20％）。年轻患者接受MVAC的频率更高(50%vs.28%)，而老年人接受更多GC(34%vs.47%）或非顺铂化疗（16%vs.24%）（P=.02）。总的来说,不同年龄段的pOR和pCR相似(52%vs.47%；P=0.5和10%vs.8%；P=.7）。虽然GC和非顺铂化疗显示较低的pCR为5％和3％，分别,MVAC显示pCR为17％（P=0.03），并且与较高的pCR独立相关（OR4.31；P=0.03）。Kaplan-Meier分析显示无复发生存率和癌症特异性生存率无差异。而老年人的总生存率较低。
患有高风险UTUC的老年患者在RNU之前有资格接受基于顺铂的NAC治疗，可能与年轻患者一样受益于这种多模式治疗。顺铂不合格的患者接受非顺铂为基础的NAC似乎有较低的反应率，应考虑立即RNU。
