High sensitivity urine biomarkers to detect bladder cancer

29 November 2016

An investigational, follow-up study by Greek researchers on three urine biomarkers to detect bladder cancer (BCa) has won the first prize for the best unmoderated poster at the recently concluded 8th European Multidisciplinary Meeting on Urological Cancers (EMUC16) held in Milan over the weekend.

Lead author Charalampos Fragkoulis of the G. Gennimatas Hospital, Dept. of Urology, in Athens, Greece took the honour and presented his study,  titled “Multiple reaction monitoring study for bladder cancer diagnosis using novel urine biomarkers,” during the closing plenary session of EMUC16.

“We have previously identified three proteins, SPARC, SLIT-2 and profilin-1 as potential biomarker candidates for BCa diagnosis by proteomic analysis. In this study we investigated further the diagnostic performance of these proteins by analyzing them through Multiple Reaction Monitoring (MRM),” said Fragkoulis.

There is a lack of a specific biomarker of invasive bladder cancer, considered as the seventh most commonly diagnosed cancer among men, worldwide. Fragkoulis said that in most cases patients have non-muscle invasive disease, although 25% of patients are initially diagnosed with a muscle invasive status.  Following initial treatment, BCa patients with a non-muscle invasive are monitored by cystoscopy and urinary cytology tests.

In their study, a total of 65 urine samples from BCa patients and 32 urine samples from control patients were collected. BCa stage was Ta in 23 patients, T1 in 18 and T2+ in 24 patients. The investigators developed a multiplex assay and specificity was confirmed by using synthetic isotope labeled peptides as internal standards.

The results showed that in all cases the levels of all three potential biomarkers (SPARC, SLIT-2, profiling-1) increased with tumor stage. The MRM assay showed high reproducibility and accuracy and was also not affected by concomitant proteinuria.

“By combining the measurements of the 3 biomarkers a classifier was created and it discriminated high stage (T2+) BCa patients by all other groups with high specificity and sensitivity,” the researchers wrote.

“The combination of the three novel urine biomarkers (SPARC, SLIT-2, profiling-1) assessed by Multiple Reaction Monitoring (MRM) presents high sensitivity as well as specificity in the diagnosis of high stage BCa (stage T2+),” said Fragkoulis.

Second prize (Abstract P157) went to a study by Carlo Buonerba and colleagues which looked into the prognostic classification of patients with advanced penile squamous cell carcinoma (PSCC) receiving salvage systemic treatment.  Buonerba, of the University Federico II of Naples, Dept. of Clinical Medicine, Naples, Italy, said their study is the first prognostic classification proposed for patients receiving salvage systemic therapy for advanced penile squamous cell carcinoma (PSCC).

“The presence of VM and Hb ≤10 gm/dl was associated with poor OS and PFS. Cetuximab appeared to be associated with better RR. This prognostic model may assist in salvage therapy drug development for this orphan disease by improving interpretation of outcomes seen in non-randomized data,” the researchers said.

A multi-institutional study conducted by radiation oncologists led by Sang Jun Byun (Abstract P126) from Seoul, South Korea won the third prize which investigated bladder-preserving therapy for stage Ⅱ to Ⅳ bladder cancer.

In their study, Byun said 69 patients (45.4%) showed complete response to radiotherapy and 46 (30.3%) did partial response. Five-year overall survival rate (OS) was 45.8% and 5-year disease specific survival rate (DSS) was 48.9%.

“We thought our survival rates were comparable to those of other studies. Bladder cancer detection before getting older may influence the better survival outcomes. It is suggested that further randomized studies are needed to be elucidate the impact of radiotherapy in bladder cancer,” the researchers wrote.