背景:目前,非肌层浸润性膀胱癌(NMIBC)的临床诊断策略,如膀胱镜检查和细胞学检查是侵入性的和/或准确性有限.泌尿,尿中突变和甲基化生物标志物的检测,在检测血尿的上尿路癌(UTUC)患者中显示出很高的准确性。这项研究的目的是评估尿液在NMIBC患者诊断中的表现。
方法:在这项多中心前瞻性研究中,共纳入203名患者,包括60例血尿患者和143例接受复发监测的NMIBC患者。在膀胱镜检查之前收集尿液样本以进行尿液测试。在血尿队列和复发监测队列中,将尿液表现与临床标准方法进行比较,分别。此外,对NMIBC患者进行随访,中位时间为20.5个月(范围为0.03至24.03个月),以评估在复发监测期间尿液的预测价值。
结果:对于膀胱癌诊断,OncoUrine检测了47个样本,其敏感性/特异性/阳性预测值(PPV)/阴性预测值(NPV)为80%(95%CI44.2-96.5)/91.9%(95%CI77.0-97.9)/72.7%(95%CI39.3-92.7)/94.4%(95%CI80.0-99.0)(kappa值69.4%,95%CI44.4-94.3),表明72.3%不必要的膀胱镜检查。对于复发诊断,尿液测试了93个样本,敏感性/特异性/PPV/NPV为100%(95%CI59.8-100.0)/68.2%(95%CI57.1-77.7)/22.9%(95%CI11.0-40.6)/100%(95%CI92.3-100.0)(卡伯值27.0%,95%CI11.1-42.8),表明62.4%的保留膀胱镜检查。更重要的是,在12/25(48%)的患者中,Oncouine正确预测了80%(20/25)的最终复发,但膀胱镜检查阴性随访期间复发。结果与NMIBC患者的无复发生存率(RFS)显著相关(中位数34.4个月vs未达到;HR6.0,95%CI2.7-13.5,P<0.0001)。
结论:尿癌显示出降低膀胱癌患者不必要的膀胱镜检查频率和医疗费用的潜在价值。测试结果阳性的患者代表复发风险高的人群,因此应进行频繁的监测以确保及时发现任何潜在的复发。这项研究已在ClinicalTrials.gov上注册,编号NCT04994197于2021年8月发布。
Currently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as
cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection of upper tract urinary carcinoma (UTUC) patients with hematuria. The aim of this study is to evaluate the performance of OncoUrine in diagnosis of NMIBC patients.
In this multicenter prospective study, a total of 203 patients were enrolled, including 60 patients present with hematuria and 143 NMIBC patients under recurrence surveillance. Urine samples were collected before
cystoscopy to undergo OncoUrine test. OncoUrine performance was calculated compared to clinical standard methods in hematuria cohort and recurrence surveillance cohort, respectively. Furthermore, NMIBC patients were followed up with a median time of 20.5 months (range 0.03 to 24.03 months) to assess the predictive value of OncoUrine during recurrence monitoring.
For bladder cancer diagnosis, OncoUrine tested 47 samples and achieved a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 80% (95% CI 44.2-96.5)/91.9% (95% CI 77.0-97.9)/72.7% (95% CI 39.3-92.7)/94.4% (95% CI 80.0-99.0) (kappa value 69.4%, 95% CI 44.4-94.3), indicating 72.3% of unnecessary
cystoscopy. For recurrence diagnosis, OncoUrine tested 93 samples, and the sensitivity/specificity/PPV/NPV was 100% (95% CI 59.8-100.0)/68.2% (95% CI 57.1-77.7)/22.9% (95% CI 11.0-40.6)/100% (95% CI 92.3-100.0) (kappa value 27.0%, 95% CI 11.1-42.8), indicating 62.4% of spared cystoscopy. What is more, OncoUrine correctly predicted 80% (20/25) of final recurrence with 12/25 (48%) patients who were OncoUrine positive, but
cystoscopy negative was followed with recurrence during follow-up. The test result of OncoUrine was also found significantly correlated with recurrence free survival (RFS) of NMIBC patients (median 34.4-month vs unreached; HR 6.0, 95% CI 2.7-13.5, P < 0.0001).
OncoUrine showed potential value to reduce the frequency of unnecessary
cystoscopy and the healthcare cost of bladder cancer patients. Patients with positive test results represented a population who were at high risk of recurrence and thus should be subject to frequent surveillance to ensure timely detection of any potential recurrence. This study has been registered in ClinicalTrials.gov with the number NCT04994197 posted on August 2021.