Macchi Alberto, Bruniera Martina, Nazzani Sebastiano, Ceccato Tommaso, Colbacchini Claudia, Taverna Alessandra, Aiello Giuseppe, Bernasconi Valentina, Catanzaro Mario, Torelli Tullio, Biasoni Davide, Stagni Silvia, Tesone Antonio, Silvani Carlo, Claps Melanie, Giannatempo Patrizia, Zimatore Matteo, Bonini Chiara, Morelli Daniele, Nicolai Nicola
Urologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Urologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Clin Genitourin Cancer. 2025 Jun;23(3):102333. doi: 10.1016/j.clgc.2025.102333. Epub 2025 Mar 19.
Non-muscle-invasive bladder cancer (NMIBC) patients need a strict follow-up with cystoscopy (UCS) and voided urinary cytology (vUC) due to high rate of recurrence and progression. To reduce invasiveness and costs, a new diagnostic biomarker, namely Xpert Monitor BC-detecting 5 mRNAs in voided urine-, has been proposed. We test Xpert Monitor BC ability to detect tumor recurrence at an early point during follow-up of high risk (HR) or very high risk (VHR) NMIBC patients, aiming at evaluating reliability of this test as a single procedure.
Between September 2022 and July 2023 included, 80 HR or VHR NMIBC patients were prospectively enrolled. Both naïve and previously treated patients (including Bacillus Calmette-Guérin-BCG-and/or systemic immunotherapy) were admitted. Patients with known upper urinary tract urothelial carcinoma (UTUC) were excluded. Xpert Monitor BC test was carried out on precystoscopy voided urine samples. In case of suspicious urethra-cystoscopy (UCS), a transurethral resection (TURB) or a biopsy was indicated. vUC was usually prescribed to be performed prior to UCS. Negative predictive value (NVP), positive predictive value (PPV), sensitivity (SE) and specificity (SP) of Xpert Monitor BC and vUC, were assessed and compared with UCS and secondarily with histology at TURB/bladder biopsy. Patients who proceeded with follow-up underwent a second evaluation with Xpert Monitor BC test.
Seventy-six patients were evaluable. Median age was 70 years (interquartile range [IQR] 65-78) and 62 (81.6%) patients were male. VHR patients were 14 (18.4%), 47 (61.8%) had a history of carcinoma in situ (CIS) and 37 (49.3%) had multifocal disease while 51 patients (67.1%) had recurrent bladder cancer (BC). BC recurred in 15 patients (19.7%): in 3 of them as a muscle-invasive bladder cancer (MIBC). Xpert Monitor BC showed a NPV, PPV, SE, SP of 95.3% (41/43), 57.6% (19/33), 90.5% (19/21) and 74.5% (41/55) respectively. When available, vUC displayed a NPV of 78.9% (30/38), a PPV of 75% (3/4), a SE of 27.3% (3/11) and a SP of 96.7% (30/31). Twenty patients underwent a subsequent Xpert Monitor BC test and UCS during their follow-up, and 3 had a bladder cancer recurrence. Of note Xpert Monitor BC was positive in all those 3 patients who previously tested positive despite a negative UC.
High NPV and SE of Xpert Monitor BC are confirmed in our HR and VHR NMIBC series. Apparent false positive tests may be regarded as suspicious for persistent/recurrent disease. Implementation of Xpert Monitor BC aiming at improving cancer detection is supported by these findings, and a single test based follow-up may be explored.
非肌层浸润性膀胱癌（NMIBC）患者由于复发和进展率高，需要通过膀胱镜检查（UCS）和尿脱落细胞学检查（vUC）进行严格随访。为了减少侵入性和成本，一种新的诊断生物标志物，即Xpert Monitor BC（可检测晨尿中的5种mRNA）已被提出。我们测试了Xpert Monitor BC在高危（HR）或极高危（VHR）NMIBC患者随访早期检测肿瘤复发的能力，旨在评估该检测作为单一程序的可靠性。
在2022年9月至2023年7月期间，前瞻性纳入了80例HR或VHR NMIBC患者。初治患者和既往接受过治疗的患者（包括卡介苗[BCG]和/或全身免疫治疗）均纳入研究。排除已知上尿路尿路上皮癌（UTUC）的患者。在膀胱镜检查前的晨尿样本上进行Xpert Monitor BC检测。如果尿道膀胱镜检查（UCS）可疑，则进行经尿道切除术（TURB）或活检。vUC通常在UCS之前进行。评估Xpert Monitor BC和vUC的阴性预测值（NVP）、阳性预测值（PPV）、敏感性（SE）和特异性（SP），并与UCS进行比较，其次与TURB/膀胱活检的组织学结果进行比较。进行随访的患者接受了第二次Xpert Monitor BC检测评估。
76例患者可评估。中位年龄为70岁（四分位间距[IQR]65 - 78），62例（81.6%）为男性。VHR患者14例（18.4%），47例（61.8%）有原位癌（CIS）病史，37例（49.3%）有多灶性病变，51例（67.1%）有复发性膀胱癌（BC）。15例患者（19.7%）出现BC复发：其中3例为肌层浸润性膀胱癌（MIBC）。Xpert Monitor BC的NVP、PPV、SE、SP分别为95.3%（41/43）、57.6%（19/33）、90.5%（19/21）和74.5%（41/55）。在可行的情况下，vUC的NVP为78.9%（30/38），PPV为75%（3/4），SE为27.3%（3/11），SP为96.7%（30/31）。20例患者在随访期间接受了后续的Xpert Monitor BC检测和UCS，3例出现膀胱癌复发。值得注意的是，在这3例患者中，尽管UC为阴性，但之前检测为阳性的所有患者Xpert Monitor BC均为阳性。
在我们的HR和VHR NMIBC系列中，Xpert Monitor BC的高NVP和SE得到证实。明显的假阳性检测结果可能被视为持续性/复发性疾病的可疑情况。这些发现支持实施Xpert Monitor BC以改善癌症检测，并且可以探索基于单一检测的随访方案。
