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Nephron Sparing Treatment (NEST) for small renal masses: A feasibility cohort-embedded randomised controlled trial comparing percutaneous cryoablation and robot-assisted partial nephrectomy

  • Joana B. Neves,
  • Hannah Warren,
  • Joseph Santiapillai,
  • Nicola Rode,
  • David Cullen,
  • Menelaos Pavlou,
  • Miles Walkden,
  • Prasad Patki,
  • Ravi Barod,
  • Faiz Mumtaz,
  • Michael Aitchison,
  • Steven Bandula,
  • Elena Pizzo,
  • Veronica Ranieri,
  • Norman Williams,
  • William Wildgoose,
  • Kurinchi Gurusamy,
  • Mark Emberton,
  • Axel Bex,
  • Maxine G.B. Tran

https://www.europeanurology.com/article/S0302-2838(23)03012-9/fulltext


There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the CRA intervention arm, 84% consented (95% confidence interval [CI] 64–95%) and 76% (95% CI 55–91%) received CRA; 100% (95% CI 86–100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79–96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1–2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was −5.0 ml/min/1.73 m2 after CRA and −5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management.

Commentary by Dr. Riccardo Bertolo

The authors of “nephron sparing treatment (NEST) for small renal masses: A feasibility cohort-embedded randomised controlled trial comparing percutaneous cryoablation and robot-assisted partial nephrectomy” [1] introduced their research highlighting the existing scarcity of high-level evidence on small renal masses (SRMs) management due to previous randomised controlled trials (RCT) failing to meet accrual targets [2, 3].

Neves et al. described a study to evaluate the feasibility of recruiting participants for a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN) in the management of SRMs.

What is a cohort-embedded RCT? It is an evolution of post-randomisation consent RCTs, that overcome ethical concerns by asking cohort participants to consent to be the ‘‘control’’ arm and receive the standard of care in embedded trials [4]. It is a type of clinical trial design that combines elements of both an RCT and a cohort study. In a traditional RCT, the participants are randomly assigned to different interventions, and outcomes are then compared between the groups, while in cohort studies, participants are followed over time to observe the development of outcomes based on their exposure to certain factors.

In a cohort-embedded RCT, researchers embed a randomised controlled trial within a larger cohort study. The cohort provides participants already being observed for a particular outcome or condition. Within this cohort, a subgroup is selected to participate in a randomised controlled trial. In summary, such study design is considered valuable when researchers want to capitalise on an existing cohort study but also wish to investigate the causal effects of specific interventions. Indeed, the cohort-embedded RCT allows for collecting both observational and experimental data within the same study framework, providing a more comprehensive understanding of the research question.

The present study successfully recruited 200 participants to the cohort, with 50 individuals enrolled in the RCT. The authors underlined high participation rates in the CRA intervention arm, with 84% of patients consenting and 76% undergoing cryoablation. In the control arm, 100% of participants underwent RPN. The retention rate at 6 months was reported to be 90%.

The study’s results also provide us with insights into the procedures and outcomes. In the RPN group, 8% were converted intraoperatively to radical nephrectomy, and postoperative complications (Clavien-Dindo grade 1–2) occurred in 12% of the CRA group and 29% of the RPN group. The median duration of hospitalisation was shorter for CRA compared to RPN (1 vs. 2 days). Additionally, at 6 months, both interventions showed a decrease in renal function, with CRA resulting in a mean change of -5.0 ml/min/1.73 m² versus -5.8 ml/min/1.73 m² s/p RPN.

Conclusion

The authors of the study suggest the feasibility of a cohort-embedded RCT comparing  a less popular ablative therapy, CRA (cryoablation robotic partial nephrectomy), versus the so-called “standard of care” RPN. The data collected in this study are positioned to inform future multicentre trials on the management of SRMs.

Future efforts will have to ensure there is equipoise in selecting treatment with CRA or RPN for all patients. Moreover, multicentric collaboration could better help in targeting the sample size needed to observe significant differences between the management strategies.

References

[1] Neves JB, Warren H, Santiapillai J, et al. Nephron sparing treatment (NEST) for small renal masses: A feasibility cohort-embedded randomised controlled trial comparing percutaneous cryoablation and robot-assisted partial nephrectomy. Eur Urol. 2023 Sep 6:S0302-2838(23)03012-9. doi: 10.1016/j.eururo.2023.07.012. Epub ahead of print. PMID: 37684178.

[2] https://www.isrctn.com/ISRCTN31161700

[3] https://classic.clinicaltrials.gov/ct2/show/NCT01608165

[4] Zelen M. A new design for randomised clinical trials. N Engl J Med 1979;300:1242–5.