In this rapid-fire debate, the focus is on the management of retroperitoneal lymphadenopathy that has a partial response to platinum-based chemotherapy. Dr. Seth Lerner argues for surgical consolidation, while Dr. Thomas Powles argues for systemic therapy.
This is a 52 woman who presented with hematuria, she has no significant previous medical history. She has a bladder tumor of cystoscopy. TURBT demonstrates a high-grade urothelial cancer with muscle invasion. CT scan demonstrates cT3N3M1a (enlarged nodes up to renal vein). PET scan demonstrates no distant metastases.
Starts accelerated ddMVAC. CT scan after 3 cycles shows a reduction in tumor size and lymph nodes. Continues treatment to 6 cycles.
Wants to “do everything available” to survive the disease.
Dr. Lerner discusses the role of consolidated surgery. First, he notes that the PET/CT only has modest diagnostic improvement compared to CT alone and that metabolic complete response (CR) in nodes or overall disease is not associated with cancer-specific survival (CSS) benefit.
In his practice, the partial response in the nodes would warrant a 2nd line systemic therapy prior to surgery – consider a checkpoint inhibitor. If there is a stable disease burden, he would then consider surgery.
Ultimately he indicated that you need to assess both the response in the bladder as well as the response and the lymph nodes.
- 25-50% of patients with cN+ disease will have a complete pathologic nodal response to chemotherapy
- Bladder and node response is not concordant
Patients with pathologic CR in nodes have better disease-free survival (DFS) compared to patients with residual disease – but 5-year DFS is still 18-24%.
He then looked at the extent of nodal disease. Patients with N2-3 disease had survival outcomes similar to that of M1 patients.
Patients will do best if they have a good response in both the nodes and in the bladder, rather than node by itself.
Even in a high volume center and experienced hands, outcomes for retroperitoneal lymph node dissection (RPLND) for post-chemotherapy residual nodes in mUC is not great – median 14 months progression-free survival (PFS) and 21 months DFS.1 Only 1 in 7 patients was alive at 2 years.
However, in a well-counseled patient, he indicated his approach:
1. TURBT – if no residual disease after 6 cycles, radiation may be an alternative to cystectomy for local control
- Can consider RPLND/PLND alone. If negative, manage bladder without RC or radiotherapy (XRT)
- If residual disease in bladder, then need RC for consolidation
2. RPLND following the template of pre-chemotherapy adenopathy
- Para-aortic, interaortocaval, retrocaval
- Frozen sections – if negative, proceed distally
- Common iliac, pelvis also with frozen sections
- If negative, proceed with cystectomy (or XRT if prior TURBT negative)
- If any frozen section positive, do not proceed
He strongly recommended this paper by Bernie Bochner as a must-read.2
Dr. Powles had the slightly easier job of arguing for additional systemic therapy.
First, he referred to the JAVELIN Bladder 100 study (he is the senior author)3 as level 1 evidence for switch IO therapy for persistent disease / mUC following cisplatin-based chemotherapy. There is a clear OS benefit (~7 months) to the addition of avelumab to best supportive care. This benefit was seen regardless of response to first-line chemotherapy.
He did comment on the potential prognostic impact of ctDNA if it was available. Ct DNA in this patient, if positive, may have suggested persistent active disease and favored systemic therapy as well – as these patients have a poorer prognosis than ctDNA negative patients.
Overall, I think the general consensus is that there is strong data for continued systemic therapy. The surgical approach should be in a multidisciplinary setting and in highly selected well-counseled patients.
Michiel S. Van Der Heijden, PhD, Medical Oncologist and Research Group Leader, at the Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
Seth Lerner, MD, FACS, Professor Urology at Baylor College of Medicine Houston, TX
Thomas Powles, MD, MBBS, MRCP, Professor of Genitourinary Oncology, Director, Barts Cancer Centre, Lead for Solid Tumour Research London, UK
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
1. Liu NW, Murray KS, Donat SM, Herr HW, Bochner BH, Dalbagni G. The Outcome of Post-Chemotherapy Retroperitoneal Lymph Node Dissection in Patients with Metastatic Bladder Cancer in the Retroperitoneum. Bladder Cancer. 2019 Jan 31;5(1):13-19. doi: 10.3233/BLC-180186. PMID: 30854412; PMCID: PMC6401561.
2. Bochner BH. Lymph Node Dissection for Advanced Bladder Cancer: Is There a Role? Eur Urol Focus. 2020 Jul 15;6(4):615-616. doi: 10.1016/j.euf.2019.09.008. Epub 2019 Sep 21. PMID: 31551141.
3. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18. PMID: 32945632.