RAZOR

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Parekh DJ, et al. "Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial". The Lancet. 2018. 391(10139):2525-2536.
PubMedFull text

Clinical Question

In patients with bladder cancer treated with cystectomy, is progression free survival inferior when comparing robotic and open surgery?

Bottom Line

Among adults with bladder cancer, robotic cystectomy appears to be non-inferior to open cystectomy in terms of progression free survival

Major Points

Radical cystectomy is surgical standard for invasive bladder cancer. This paper presents a randomised, open-label, non-inferiority trial, phase 3, multicenter in USA. The 2-year progression-free survival was 72.3% in robotic cystectomy group and 71.6% in the open cystectomy group. Estimated blood loss was significantly lower in robotic when compared to open cystectomy. Post-operative blood transfusion rates were significantly lower in the robotic cystectomy group, as was length of stay. Shorter operating timewas observed in the open cystectomy group. There were no significant differences in complication rates. The investigators were unable to assess cost differences between the two procedures.

Guidelines

The current (as at September 2018) European Association of Urology guidelines state that: "Radical cystectomy is considered a reasonable option in patients with non muscle invasive bladder cancer (NMIBC), though the decision making should give consideration to the considerable morbidity." [1].

The guidelines relating to muscle invasive bladder cancer (MIBC) state that cystectomy is the recommended approach for treatment. In regards to open vs robotic, there are a number of recommendations made including the need to have an informed discussion about open vs robotic surgery; and the principle of selecting experienced centres rather than specific techniques.

Design

  • Phase III open label, randomised, non-inferiority
  • N=350
    • Robotic surgery (n=176)
    • Open surgery (n=174)
  • Setting: 15 centers in the United States
  • Enrollment: July 1 2011 to November 18 2014
  • Mean follow-up: not reported (minimum followup of 2 years)
  • Analysis: Per Protocol, with sensitivity analysis of Intention-to-treat
  • Primary outcome: non-inferiority progression free survival

Population

Inclusion Criteria

  • Patients were eligible if they were aged 18 years or older (<99); and
  • had biopsy-proven clinical stage T1–T4, N0–N1 (AJCC 7th edition) ,
  • M0 bladder cancer or refractory carcinoma in situ.
  • Written informed consent was obtained from all patients


Exclusion Criteria

  • Patients who had previously had open abdominal or pelvic surgery or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded.
  • Pregnant women were also excluded.

Baseline Characteristics

No baseline characteristics are highlighted as being statistically different between treatment groups. Data below for the Robotic group

  • Men (84%)
  • BMI median 27.8
  • ECOG 0 78%
  • Stage <=T2 87%
  • Perioperative chemotherapy 41%
  • Neoadjuvant chemotherapy 27%
  • Baseline haemoglobin mean 13.05

Interventions

  • Patients centrally randomly assigned (1:1) via a web-based system, to receive open cystectomy or robotic cystectomy.
  • Each institution was considered a block, stratification occured by:
    • type of urinary diversion (incontinent or continent),
    • clinical T stage (carcinoma in situ, T1–T2, or T3–T4),
    • and Eastern Cooperative Oncology Group (ECOG) performance status (0–1, or ≥2).
  • On accrual a hierarchical decision-rule was applied, and the allocation was deterministic if certain predefined limits were exceeded, and random otherwise.

Outcomes

Primary Outcomes

Progression free survival at 2 years
Robotic 72.3% (95% CI 64.3-78.8), open: 71.6% (95% CI 63.6-78.2) in the open group.
Non inferiority p value: 0.001, log rank test p=0.90.

Secondary Outcomes

Robotic vs open surgery

Blood loss
300mL vs 700mL (p<0.0001
Perioperative transfusion
24% vs 45%, p=0.0002
Intraoperative transfusion
13% vs 34%, p<0.0001
Postoperative transfusion
25% vs 40%, p=0.0089
Hospital stay ≤5 days
29% vs 18%, p=0.0407
Length of stay, days
6 vs 7 days, p=0.0216
Operating time
428 min vs 361 min, p=0.0005
Surgical complications with 90 days, histopathological classification, T Stage, N Stage, Pathological stage, Lymph node discection, positive surgical margin.
all reported as p>0.05.
FACT-VCI domains for quality of life
all p>0.05 when comparing between groups.

Subgroup Analysis

Adverse Events

In total, adverse events were reported in 67% of robotic and 69% of open surgery participants.

Criticisms

  • The authours acknowledge that there was no central pathology review. There is also description of the site investigators being able to 'correct' the pathology, which sounds unusual.
  • 70% of the study population had organ confined disease. This may represent positive case selection
  • The authours acknowledge that there was no costing data. A key argument against robotic surgery is the excessive cost, so this is a limitation in interpreting the non-inferior outcome.
  • The selected margin of 15% for non-inferiority is open to interpretation.
  • The ascertainment statistics at each centre are not reported.
  • Measurements such as time to discharge may be subject to bias given that this is likley specified by the non-blinded surgeon.
  • Blinded – only pathology was blinded (so potentially bias in other measures e.g. time to discharge)
  • Competing risks may influence the survival measures

Funding

NIH-NCI

Further Reading

  • A systematic review of trials in this area can be found at [2]