ESUP Symposium: a multidisciplinary look at the future of bladder cancer treatment

08 November 2018

A multidisciplinary team of speakers discussed bladder cancer at the ESUP Symposium on Thursday. The Symposium was jointly organized by the EAU Section of Urological Research (ESUR)  and the European Society of Pathology Uropathology Working Group (ESUP). It took place in Amsterdam, concurrently with the 7th meeting of the EAU Section of Urological Imaging (ESUI18) and a variety of uro-oncology-related ESU Courses.

Speakers included urologists, pathologists, medical oncologists and a urological researcher, each giving the audience of around 50 different insights on bladder cancer treatment from their respective specialities. Urologist Prof. Hein Van Poppel (Leuven, BE) and pathologist Prof. Montironi (Ancona, IT) chaired the session, although the latter was briefly replaced by Prof. Antonio Lopez-Beltran (Lisbon, PT) (also a pathologist) in his absence.

Update on BCa Treatments

The symposium started with a broad and up-to-the-minute update on BCa treatment by medical oncologist Prof. Susanne Osanto (Leiden, NL). Prof. Osanto first gave an overview of the current treatment options for bladder cancer, listing some recent developments and their implications for treatment. She then highlighted some trends that point to the future of the field: the increasing importance of the molecular pathologist.

“Molecular profiling will become increasingly relevant for choosing the right treatment for our patients,” Osanto said. “They already offer prognostic or predictive markers. In future, mutations will be actionable. In 2014, Nature published a so-called ‘genomic landscape of bladder cancer’, featuring many subsets and profiles. It is not yet known if the data are strong enough, and validation will be required. This will be an expensive process.”

Looking ahead, Prof. Osanto pointed to an increased use of checkpoint inhibitors (metastatic 2L and 1L, neo and adjuvant space and even in non-muscle invasive bladder cancer). Combinations of chemo- and immunotherapy and in future systemic therapy will be used in metastatic and high-risk non-muscle invasive and invasive or metastatic bladder cancer.

“All these strategies in muscle and non-muscle invasive bladder cancer should also be tested in upper urinary tract cancers,” Prof. Osanto emphasised.

Pathology

A significant part of the Symposium was then dedicated to the pathologist’s perspective, as Dr. Maurizio Colecchia (Milan, IT) explained their methods and standards. The International Collaboration on Cancer Reporting (ICCR) has established international standards for evaluation and reporting.

“Our goals are to provide accurate macroscopic and microscopic evaluation of features with diagnostic, prognostic and therapeutic value. We then offer personalised pathology reports based on the latest international standards (ICCR). Additional tissue studies including molecular investigations for personalized therapies are strongly recommended.”

Prof. Van Poppel then raised the surgeon’s perspective, eliciting clear and practical advice from Dr. Colecchia and the other pathologists. Prof. Lopez-Beltran explained the necessity for both the ‘freshness’ of the tissue sample and its shape. “Urologists need to realise how to best deliver the specimen. I ask the clinicians in my centre to give a cut, transversal or otherwise. This allows the formalin to fully penetrate the sample, which should not be too big or surrounded by layers of fat.”

Prof. Lopez-Beltran proceeded to give an overview of changes in the bladder resulting from treatment for non-muscle invasive bladder cancer, including BCG, mitomycin-C, and also ketamine, which might have been taken in a recreative setting. Prof. Montironi then did the same for muscle-invasive.

Potential of immuno-oncology

Medical oncologist Prof. Andrea Necchi (Milan, IT) gave a talk on the role of checkpoint inhibition in bladder cancer, introduced as a particularly hot topic by Prof. Van Poppel.

Necchi gave a wide-ranging overview of the latest developments in the field of immuno-oncology (IO), citing the latest studies as presented at ESMO 2018 in Munich only days before. The first data regarding neoadjuvant use of pembrolizumab and chemotherapy for locally advanced urothelial cancer (C. Holmes et al) were briefly summarised by Necchi, who gave the personal recommendation. “In selected patients, we should really be brave and continue immunotherapy instead of complicating the process with chemotherapy. Patients are also often happy to not receive chemotherapy.”

Speaking generally and looking to the near future, Necchi pointed out that pathologic response rates observed in single-agent IO studies are promising: “but we need to confirm the association with long-term improved outcomes.”

“Chemotherapy plus IO combinations are now even more attractive in neoadjuvant setting. IO, on its own or combined, is poised to make a significant impact in the management of localised muscle-invasive disease. This requires the right trial design.”

Prof. Van Poppel latched onto Prof. Necchi’s point about recommending single rather than combined immunotherapy. Necchi conceded that there was also a commercial dimension at play between the academic perspective and the perspective of the companies. “The bigger trials are initiated by companies that have an interest in offering chemotherapy options and these trials are currently pushing developments in that direction.”