Yonover Paul M, Ward Ceressa T, Mazzarella Brian C, Phillips Kevin G, Jensen Brad W, Bicocca Vincent T, Duffy Kathleen, Yonover Jaden, Cherry Ava, Levin Trevor G
UroPartners/SolarisHealth Partners, Chicago, IL, United States.
Convergent Genomics, South San Francisco, CA, United States.
Front Urol. 2023 Aug 9;3:1229709. doi: 10.3389/fruro.2023.1229709. eCollection 2023.
Metachronous upper tract urothelial carcinoma (UTUC) is a rare yet aggressive malignancy that is often multifocal and invasive at the time of diagnosis. Unfortunately, the rarity of metachronous UTUC results in a paucity of targeted data, as current literature and clinical management of this tumor is largely extrapolated from that of bladder cancer. Urinary comprehensive genomic profiling with the UroAmp assay identifies six general classes of tumor-mutations present in the urine and thus, may aid in detecting UTUC when the limitations of current tools impede definitive diagnosis. We describe the utility of urinary comprehensive genomic profiling in confirming the provider's suspicion for metachronous UTUC and recommending radical nephroureterectomy.
A 68-year-old male with a history of recurrent carcinoma (CIS) of the bladder presented to the urology clinic in 2022 for continued surveillance. Abnormal soft tissue thickening surrounding the proximal right ureter, revealed on computerized tomography urography, prompted further evaluation. Selective right upper tract cytology was indeterminate, and urinary comprehensive genomic profiling was ordered to adjudicate. No tumor was visualized on ureteroscopy however the cytologic brush biopsy of the renal pelvis and proximal ureter were positive for urothelial carcinoma (UC) and/or CIS. UroAmp testing identified genomic features associated with high-grade UC, risk of invasion, and a high genomic disease burden.
The patient underwent a right kidney and ureter nephroureterectomy in September 2022. Surgical pathology confirmed non-invasive multifocal urothelial CIS. A postoperative urinary comprehensive genomic profiling in February and May of 2023 detected no evidence of residual disease, consistent with complete resection of the tumor. The provider will continue intensive urinary comprehensive genomic profile monitoring coupled with conventional surveillance.
Urinary measurement of mutated UC genes correlate with disease burden, pathologic grade, and invasion risk and provide clinical utility when reliance on visual confirmation and cytology were not definitive or feasible.
异时性上尿路尿路上皮癌（UTUC）是一种罕见但侵袭性强的恶性肿瘤，在诊断时通常为多灶性且具有侵袭性。不幸的是，异时性UTUC的罕见性导致针对性数据匮乏，因为目前关于该肿瘤的文献和临床管理很大程度上是从膀胱癌的文献和管理中推断而来的。使用UroAmp检测进行尿液综合基因组分析可识别尿液中存在的六种常见肿瘤突变类型，因此，当现有工具的局限性妨碍明确诊断时，可能有助于检测UTUC。我们描述了尿液综合基因组分析在确认医生对异时性UTUC的怀疑以及推荐根治性肾输尿管切除术方面的作用。
一名68岁男性，有膀胱原位癌（CIS）复发史，于2022年前往泌尿外科诊所进行持续监测。计算机断层扫描尿路造影显示右输尿管近端周围软组织异常增厚，促使进一步评估。选择性右上尿路细胞学检查结果不明确，于是进行尿液综合基因组分析以做出判断。输尿管镜检查未发现肿瘤，但肾盂和近端输尿管的细胞学刷检显示尿路上皮癌（UC）和/或CIS呈阳性。UroAmp检测确定了与高级别UC、侵袭风险和高基因组疾病负担相关的基因组特征。
该患者于2022年9月接受了右肾和输尿管根治性切除术。手术病理证实为非侵袭性多灶性尿路上皮CIS。2023年2月和5月的术后尿液综合基因组分析未发现残留疾病的证据，这与肿瘤的完全切除一致。医生将继续进行强化尿液综合基因组分析监测，并结合传统监测方法。
尿液中UC基因突变的检测与疾病负担、病理分级和侵袭风险相关，在依靠视觉确认和细胞学检查无法明确诊断或不可行时具有临床应用价值。
