Urothelial cancer: Evidence and new outcomes awaited for better decision-making

Developments in diagnostic technology, medical and surgical therapies for urothelial cancer have occurred in recent years but crucial evidence-based results are needed for bladder cancer experts to reach better treatment strategies, particularly with regards elderly patients and those with recurrent high-risk disease.

Prof. Badrinath Konety (US) gave the Societe Internationale d’Uologie (SIU) lecture which focused on non-urothelial bladder cancer such as squamous cell carcinoma and adenocarcinomas which belong to the most common types. He discussed the management of non-urothelial tumours which require a different approach since they have atypical biologic behavior and respond differently to known treatment regimens.

“Non-urothelial tumours are uncommon but when they do occur these patients often have worse prognosis,” said Konety. “The main form of therapy is radical cystectomy.”

Except in small cell carcinoma, he said it is crucial to remember that chemotherapy is the first-line of action. Among his concluding messages are that non-muscle invasive bladder cancer may respond to BCG and that some micropapillary tumours also respond to BCG, although doctors must be ready for the option of early radical cystectomy.

The value of optical enhancements for Trans-Urethral Resection of a Bladder Tumor (TURBT) was a contentious issue in the Point-counterpoint Session, with Dr. Kay Thomas (GB) taking the “No” position and Prof. Paolo Gontero (IT) arguing for the benefits of tools such as Narrow-Band Imaging (NBI) and Photodynamic diagnosis (PDD).

Thomas provided a succinct overview saying that studies often cited to show the benefits of these imaging tools are often mixed up with new and recurrent cases. “Moreover, there are multiple reporting of very positive studies,” she added.

She noted that PDD for TURBT improves diagnostic yield but the procedure is expensive, doesn’t improve outcomes and in the case of NMIBC there is no change in recurrence. Thomas said NBI is cheaper than PDD but the limitations are the same as PDD, with the same story that although NIBI improves diagnostic yield there are no improvements in the outcomes.

“What is the most important diagnostic tool in TURBT? It’s us, the surgeon. Surgical experience is an independent predictor of TURBT quality. Is TURBT with optical enhancements worth the trouble? No,” said Thomas in her closing arguments.

Meanwhile, Gontero argued the evidence is strong and the limitations of these tools are not relevant, although he prefaced his talk by conceding that TURBT remains the mainstay procedure for diagnosis and staging of bladder cancer.

In his summary message, Gontero said the cure rate of bladder cancer is highly dependent on correct diagnosis (high-risk NMIC, MIBC) and the completeness of resection (NMIBC).

“Standard while light TURBT performance remains sub-optimal at several levels,” he said. “Optimal enhancement tools have clearly shown an improved detection rate particularly at the level of lesions that are poorly viewed with white light (CIS and small papillary tumours).”

Continuing the discussion on how to better diagnose bladder tumours, Prof. Eva Comperat (FR) discussed new genetic and histological classification to direct treatment. Comperat noted that in MIBC, cisplatin-based combination of chemotherapy and surgery remains the standard and up to now there is no widely recognized second-line therapy. She then described several genomic alterations which makes personalized treatments of bladder cancer much more complex or elusive compared to other cancers.

“Classical pathology will still be the gold standard because it’s quick, cheap and precise,” she said.

In another Point-counterpoint session, Prof. Richard Sylvester presented his arguments in favor of single instillation of chemotherapy post-TURBT, which he said is statistically and clinically significant.

“The new 2016 EAU Guidelines recommend a single immediate instillation of chemotherapy be given in patients presumed to be low risk (expected EORTC Recurrence Score= 0) and to intermediate risk patients with expected EORTC Score of 4 or less than 4,” he said. He noted that the instillation should not be given to patients with an expected EORTC Recurrence Risk Score of 5 or more than 5, and to those with a prior recurrence rate of more than one recurrence per year.

Prof. Levant Turkeri (TR) took the contrary position and said post-operative single instillation (PSI) is effective only in low-risk patients where recurrence (if any) will be small (median 3 mm) papillary tumours which can be managed effectively by active surveillance.

“There are  logistic and practical difficulties to give instillations at the early post-operative period such as drug availability and patient tolerance,” Turkeri said.