Extended lymph node dissection (LND) during radical cystectomy (RC) for bladder cancer offers no advantage over standard LND with respect to time to progression (TTP) and overall survival, but is significantly associated with decreased cancer-specific mortality, according to study findings presented at the 38th Annual Congress of the European Association of Urology (EAU23) in Milan, Italy.

The findings emerged from longer follow-up of patients in a randomized phase 3 trial conducted at 16 high-volume RC centers in Germany. The trial included 401 patients with locally resectable T1G3 or muscle-invasive urothelial BCa (T2-T4aM0).

“Despite a much longer follow-up there is still no significant advantage in the primary endpoint TTP nor the secondary endpoint OS in these patients,” said study co-author Arnulf Stenzl, MD, of the University of Tuebingen, Germany. “There is a better CSS, but does that mean a better quality of life or it is only a protraction of the actual visibility of tumor progression?”

Standard LND involved the obturator and internal and external iliac nodes. Extended LND also included the deep obturator and common iliac, presacral, paracaval, interaortocaval, and para-aortal nodes up to the inferior mesenteric artery. Patients in the standard and extended LND arms had a median 19 and 31 dissected nodes. The median follow-up duration of patients remaining alive without disease recurrence was 58.4 months.

The study revealed no significant difference between extended and standard LND with respect to 5-year TTP (68% vs 60%) and 5-year OS (57% vs 51%). The 5-year CSS, however, was significantly higher with in extended group (76% vs 65%). Compared with standard LND, extended LND was significantly associated with a 35% decreased risk of cancer-specific mortality.

The investigators identified tumor recurrence in 123 patients (30%): 68 in the standard arm versus 55 patients in the extended LND group. A total of 195 patients died (49%) — 105 (52%) in the standard arm and 90 (45%) in the extended group — including 100 patients (25%) who died from bladder cancer (60 in the standard arm and 40 in the extended group).

Study findings are robust enough to affect clinical practice, Dr Stenzl said. “If you consider that this is an onco-surgical study, with all the problems with these studies in general, 401 patients is a number sufficient to answer the questions raised,” he said.

The number of suitable interventions and difficulties in documentation as well as variability in patient preferences for institutions and surgeons, patient-level information, and quality of surgeons and their teams make these types of studies difficult to conduct, he explained.

Mark Garzotto, MD, a professor of urology and radiation medicine at Oregon Health & Science University in Portland, said trials such as this one are important because in clinical practice there is so much variation that it is often impossible to know how much patients are being helped by different surgical approaches.

“Having high-quality trial data for surgical interventions is the best path forward to uniformly improve clinical care,” said Dr Garzotto, chief of the urology section at the Portland VA Medical Center. “Second, in surgical oncology, historical precedent has been that the more radical the surgery is, the better the outcome. However, numerous contemporary trials have failed to show a benefit to more extensive surgery in a number of tumor types.”

Because this trial failed to meet its primary endpoint of TTP, he said, extended dissection should not be considered for replacement of a standard LND. “Although there was a slight improvement in CSS, the overall survival was not improved, which begs the question as to whether extended dissection was in some way harmful and negated any benefit of reduced cancer recurrence,” Dr Garzotto said. “I think as imaging techniques continue to improve, metastases-directed therapy will become the new standard of care and replace extended LND for most if not all tumor types.”

“We have operated under the belief that extended lymph node dissection in patients undergoing radical cystectomy imputes a survival benefit, but the exact extent of this dissection has been debated,” said Yale Cancer Center urologist Joseph Brito, MD, an assistant professor of urology at Yale School of Medicine in New Haven, Connecticut. “In this study, the extended node group involved quite an aggressive template, including the para-aortic, interaortocaval and paracaval nodes, areas where there is generally a low likelihood for cancer spread in most patients who are candidates for radical cystectomy. The lack of improvement in overall survival in these patients may reflect morbidity associated with such an extensive dissection, validating a more conservative approach to the pelvic nodes.”

References

Heck M, Lehmann J, Amiel T, et al. Long-term results from the randomized trial LEA: Extended Versus Standard Lymph Node Dissection in Bladder Cancer Patients Undergoing Radical Cystectomy. Presented at: EAU23, Milan, Italy, March 10-13, 2023. Abstract LB07.

Gschwend JE, Heck MM, Lehmann J, et al. Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: Survival results from a prospective, randomized trial. Eur Urol. 2019;75:604-611. doi:10.1016/j.eururo.2018.09.047