- Molecular characterization – it matters!
Yet, his main take-home point is that there is growing clinical and genomic information that UTUC and lower tract bladder cancer are not the same disease process, but rather distinct entities with some shared features. The slide below highlights some of the differences between the two:
Indeed, as noted above, the fact that UTUC is part of the HNPCC (Lynch syndrome) and bladder cancer is not, indicates a slightly different development pathway. More recent work in this area has demonstrated that patients with microsatellite instability (MSI+) have higher grade tumors, inverted growth, deep pushing borders, and lymphocytic infiltrate. Work by Seth Lerner and Surena Matin (Moss et al. EU 2017) represents the first comprehensive genomic characterization of UTUC distinct from bladder cancer. This, amongst other work, will enable a better understanding of UTUC.
- Perioperative systemic therapy – chemotherapy and immunotherapy.
He briefly noted that he still feels that neoadjuvant therapy would be better than adjuvant therapy, as these relatively elderly patients would likely tolerate therapy and kidney injury better prior to nephrectomy rather than after. However, due to the lack of definitive pathology, grade and staging, he understands the rationale for the POUT authors to start with adjuvant therapy.
He does note some neoadjuvant studies in the process of starting – including the completed phase II ECOG-AGRIN EA 8141 study demonstrating 14% pCR response to NAC and 62% downstaging to <= pT1. He also acknowledged the URANUS study by the EUOG, which is estimated to accrue by Oct 2020.
While immune-checkpoints have not specifically been assessed in UTUC, he points out that many of the ICI studies for metastatic urothelial cancer studies had 14-27% of UTUC patients included. There were higher objective response rates in patients with bladder cancer than in UTUC, but patients with bladder cancer had higher tumor mutational burden, higher PD-L1 expression and increased the frequency of genomically unstable tumors. Hence, no conclusions can be drawn. POUT 2 may shed some more light on this.
- Avoid undertreatment – offer kidney-sparing treatment to appropriate patients.
- A single postoperative dose of intravesical chemotherapy after flexible URS
Presented by: Morgan Roupret, MD, Ph.D, Faculty of Medicine, Pierre and Marie Curie University, Faculté de médecine Pierre et Marie Curie, Paris, France
Written by: Thenappan Chandrasekar, MD. Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @TjuUrology, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
1. Marchioni et al. (2017) Impact of diagnostic ureteroscopy on intravesical recurrence in patients undergoing radical nephroureterectomy for upper tract urothelial cancer: a systematic review and meta‐analysis. BJU, 120 (3), 313-319.