Upper tract urothelial carcinoma comprises 5–10% of all urothelial carcinoma cases. This disease tends to have a more aggressive course than its lower urinary tract counterpart, with 60% of patients presenting with invasive disease and 30% of patients presenting with metastatic disease at diagnosis. The diagnostic workup of UTUC involves imaging with CT urogram, urine cytology, and direct visualization and biopsy of suspected lesions via ureteroscopy. Standard treatment of high-grade UTUC involves radical nephroureterectomy (RNU) and excision of the ipsilateral bladder cuff. Both the NCCN and EAU Guidelines include neoadjuvant chemotherapy as a treatment option for select patients with UTUC; however, there are no strict guidelines. Much of the rationale for neoadjuvant chemotherapy is based on extrapolation from data from muscle-invasive bladder cancer, which has demonstrated a 5-year OS benefit of 5–8%. Retrospective studies evaluating the use of NACT in urothelial carcinoma have yielded pathologic objective response rates of 48% in UTUC cohorts. The randomized Phase III POUT study noted a DFS advantage with adjuvant platinum-based chemotherapy, compared with surveillance in UTUC, of 70% vs. 51% at 2 years. Though not the standard of care, multiple studies have explored the use of perioperative immunotherapy or chemoimmunotherapy in the management of invasive urothelial carcinoma. The PURE-02 study explored the use of neoadjuvant pembrolizumab in patients with high-risk UTUC. A small study of 10 patients, it showed no significant signals of activity with neoadjuvant pembrolizumab. Another Phase II study of neoadjuvant ipilimumab and nivolumab in cisplatin-ineligible UTUC yielded more promising findings, with 3/9 patients attaining a pathologic CR and the remaining six pathologically downstaged. The ABACUS trial found a 31% pathologic complete response rate amongst cisplatin-ineligible MIBC patients treated with neoadjuvant atezolizumab. The use of adjuvant immunotherapy has been explored over three phase III trials. The CheckMate-274 trial found a DFS benefit with the addition of one year of adjuvant nivolumab in patients with high-risk urothelial carcinoma. The IMvigor-010 study of adjuvant atezolizumab was a negative study. The AMBASSADOR trial of adjuvant pembrolizumab is pending results. With the FDA approval of erdafitinib in metastatic urothelial carcinoma, similar targets have been explored for use in perioperative use in invasive urothelial carcinoma, as with adjuvant infigratinib in the PROOF-302 trial. As the treatment paradigm for urothelial carcinoma evolves, further prospective studies are needed to expand the perioperative treatment landscape of UTUC.
上尿路尿路上皮癌占所有尿路上皮癌病例的5-10%。相较于下尿路尿路上皮癌，该疾病往往具有更强的侵袭性，60%的患者在诊断时已出现浸润性疾病，30%的患者已发生转移。上尿路尿路上皮癌的诊断检查包括CT尿路造影、尿液细胞学检查，以及通过输尿管镜对可疑病变进行直接可视化和活检。高级别上尿路尿路上皮癌的标准治疗是根治性肾输尿管切除术及同侧膀胱袖状切除。美国国家综合癌症网络和欧洲泌尿外科协会指南均将新辅助化疗作为部分上尿路尿路上皮癌患者的治疗选择之一，但尚无严格指南。新辅助化疗的许多理论依据是基于对肌层浸润性膀胱癌数据的推断，该数据显示其可带来5-8%的5年总生存获益。评估新辅助化疗在尿路上皮癌中应用的回顾性研究显示，上尿路尿路上皮癌队列的病理客观缓解率为48%。随机III期POUT研究指出，与监测相比，上尿路尿路上皮癌患者使用基于铂类的辅助化疗在2年时具有无病生存优势（70%对51%）。尽管并非标准治疗，多项研究已探索在浸润性尿路上皮癌治疗中应用围手术期免疫治疗或化疗免疫联合治疗。PURE-02研究探索了在高危上尿路尿路上皮癌患者中使用新辅助帕博利珠单抗。这项仅纳入10名患者的小型研究显示，新辅助帕博利珠单抗未产生显著活性信号。另一项在不适合顺铂治疗的上尿路尿路上皮癌患者中评估新辅助伊匹木单抗联合纳武利尤单抗的II期研究取得了更有希望的结果：9名患者中有3名达到病理完全缓解，其余6名患者病理分期降低。ABACUS试验发现，在不适合顺铂治疗的肌层浸润性膀胱癌患者中，使用新辅助阿替利珠单抗治疗的病理完全缓解率为31%。辅助免疫治疗的应用已在三项III期试验中得到探索。CheckMate-274试验发现，在高危尿路上皮癌患者中加用一年辅助纳武利尤单抗可带来无病生存获益。评估辅助阿替利珠单抗的IMvigor-010研究结果为阴性。评估辅助帕博利珠单抗的AMBASSADOR试验结果尚未公布。随着厄达替尼获得美国食品药品监督管理局批准用于转移性尿路上皮癌，类似靶点药物在浸润性尿路上皮癌围手术期的应用也得到探索，例如PROOF-302试验中评估的辅助英菲格拉替尼。随着尿路上皮癌治疗模式的演变，需要进一步的前瞻性研究来拓展上尿路尿路上皮癌的围手术期治疗格局。
Overview, Diagnosis, and Perioperative Systemic Therapy of Upper Tract Urothelial Carcinoma
肿瘤(癌症)患者之家