Editorial Comment on: “Robotic vs Laparoscopic Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multicenter Propensity-Score Matched Pair “tetrafecta” Analysis (ROBUUST Collaborative Group)” by Veccia et al.

Recommended surgical management of high-risk upper tract urothelial carcinoma (UTUC) has conventionally been approached through an open technique with radical nephrectomy, ureterectomy, complete excision of bladder cuff, template-based lymph node dissection, and instillation of perioperative chemotherapy. Five-years overall survival can vary from <20% to 75%, with increasing age being a negative prognostic factor. ¹ The approach to radical nephroureterectomy (RNU) is varied and includes open, pure laparoscopic, hand-assisted, and robot-assisted techniques.

With a rise in minimally invasive alternatives to genitourinary pathologies, the management of UTUC transformed after the initial description of the laparoscopic approach in 1991 by Clayman et al. ² With the advantages of decreased blood loss, shorter length of stay, fewer surgical complications, and less postoperative pain, laparoscopic RNU became popularized. ^3,4 Despite these advantages, controversy exists as to the oncologic efficacy of the pure laparoscopic approach. A systematic review evaluating the laparoscopic to the open approach found inferior oncologic outcomes in patients wherein the bladder cuff was managed laparoscopically. ⁵

The evolution of robot-assisted RNU from port placement strategies ⁶ to the feasibility of single docking without repositioning ⁷ across multiple robotic platforms ^8,9 has transformed the landscape by preserving the inherent advantages of the laparoscopic approach and by facilitating the dissection to the distal ureter and bladder cuff. ^10,11 In fact, adoption of robot-assisted RNU has increased substantially coupled with a decline in the open approach. ^12,13 Outcomes of robot-assisted RNU are excellent with decreasing operative times, lower blood loss, and minimal complications, while maintaining oncologic efficacy. ^14,15

In this multicenter retrospective case series, the authors adapted a popular term in the uro-oncologic literature known as “tetrafecta” to describe occurrence of bladder cuff excision, lymph node dissection, postoperative complications, and negative surgical margins. The authors found that the laparoscopic approach was associated with inferior rates of achieving “tetrafecta.” ¹⁶ The data garnered from this multicenter international cohort of expert surgeons are impressive to say the least, amassing 668 robotic RNUs and 173 laparoscopic RNUs. The authors provide granular data in terms of rates of bladder cuff excision, lymph node dissection, complications, and surgical margins.

The article should be viewed in context of its limitations, however. First, there was significant heterogeneity between the two populations with more adverse features noted in the laparoscopic cohort (higher stage, rates of cigarette smoking, CKD >3, hydronephrosis, history of bladder cancer, and clinical nodal staging). To compensate for these differences, the authors employed propensity matching that still revealed insignificant, but substantial, differences favoring the robotic group. Moreover, the laparoscopic RNU cohort may have been clinically understaged given the lower rates of preoperative biopsy (54.6% vs 49.4%, p = 0.02, after matching).

Although the aim of the article was not to compare oncologic outcomes between the two approaches, this is key in deciphering superiority. If oncologic outcomes are consistently inferior in the robotic group, the value of achieving “tetrafecta” outcomes diminishes substantially. The rates of bladder cuff excision were higher in the robotic RNU cohort (81.9% vs 63.7%), but occurrence and adequacy are two separate entities. At the 3-month follow-up cystoscopy, did the authors note any portion of the intramural ureter or presence of a ureteral stump?

Fate of a residual ureteral stump can lead to inferior overall survival, cancer-specific survival, local recurrence-free survival, distant recurrence-free survival, and bladder recurrence-free survival. ¹⁷ Performing lymph node dissection is more common when utilizing the robotic approach ¹⁸ and likely more facile. In this series, no specific template-based lymph node dissection was employed likely secondary to the multicenter multisurgeon study design. We feel a template based on tumor location is important and have previously published our Wake Forest experience in video format. ¹¹

We feel perioperative instillation of chemotherapy should be added to the “tetrafecta” to make it a “pentafecta.” In this series, low rates of adjuvant bladder instillation were found (20% in robotic RNU vs 26.4% in laparoscopic RNU) likely owing to the retrospective nature, practice patterns, and delays in implementation of guideline-changing data. Future studies on more contemporaneous data will likely have greater rates of perioperative instillation of chemotherapy. Currently, at Wake Forest we have an ongoing multicenter prospective trial evaluating gemcitabine instilled perioperatively (NCT04398368).

In summary, this group of expert surgeons should be commended on achieving “tetrafecta” outcomes in both the laparoscopic and robotic cohorts. The study highlights the inherent advantages of the robotic approach—cuff excision, no intraoperative repositioning, single docking, ease of cystotomy closure, and lymph node dissection. With rise in robotic RNU, it may be difficult for future studies to adequately compare these two techniques owing to the decline in laparoscopic RNU.