Data offer persuasive evidence to abandon minimally invasive surgery in management of early-stage cervical cancer
Melamed A, Margul DJ, Chen L, et al. Survival after minimally invasive radical hysterectomy for early-stage cervical cancer. N Engl J Med. 2018;379:1905-1914.
Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med. 2018;379:1895-1904.
Over the past decade, gynecologic cancer surgery has shifted from what routinely were open procedures to the adoption of minimally invasive techniques. Recently, a large, well-designed prospective study and a large retrospective study both demonstrated worse outcomes with minimally invasive radical hysterectomy (MIRH) as compared with traditional open radical abdominal hysterectomy (RAH). These 2 landmark studies, initially presented at the Society of Gynecologic Oncology's 2018 annual meeting and later published in the New England Journal of Medicine, have really affected the gynecologic oncology community.
Shorter overall survival in women who had MIRH
Melamed and colleagues conducted a large, retrospective US-based study to evaluate all-cause mortality in women with cervical cancer who underwent MIRH compared with those who had RAH.6 The authors also sought to evaluate national trends in 4-year relative survival rates after minimally invasive surgery was adopted.
The study included 2,461 women who met the inclusion criteria; 49.8% (1,225) underwent MIRH procedures and, of those, 79.8% (978) had robot-assisted laparoscopy. Most women had stage IB1 tumors (88%), and most carcinomas were squamous cell (61%); 40.6% of tumors were less than 2 cm in size. There were no differences between the 2 groups with respect to rates of positive parametria, surgical margins, and lymph node involvement. Administration of adjuvant therapy, in those who qualified, was also similar between groups.
Results. At a median follow-up of 45 months, 94 deaths occurred in the minimally invasive group and 70 in the open surgery group. The risk of death at 4 years was 9.1% in the minimally invasive group versus 5.3% in the open surgery group, with a 65% higher risk of death from any cause, which was highly statistically significant.
Prospective trial showed MIRH was associated with lower survival rates
From 2008 to 2017, Ramirez and colleagues conducted a phase 3, multicenter, randomized controlled trial to prospectively establish the noninferiority of MIRH compared with RAH.7 The study included 631 women from 33 centers. The prespecified expected disease-free survival rate was 90% at 4.5 years.
To be included as a site, centers were required to submit details from 10 minimally invasive cases as well as 2 unedited videos for review by the trial management committee. In contrast to Melamed and colleagues' retrospective study, of the 319 procedures that were classified as minimally invasive, only 15.6% were robotically assisted. Similarly, most women had stage IB1 tumors (91.9%), and most were squamous cell carcinomas (67%). There were also no differences in the postoperative pathology findings or the need for adjuvant therapy administered between groups. The median follow-up was 2.5 years.
Results. At that time there were 27 recurrences in the MIRH group and 7 in the RAH group; there were also 19 deaths after MIRH and 3 after RAH. Disease-free survival at 4.5 years was 86% with MIRH versus 96.5% with RAH. Reported 3-year disease-free survival and overall survival were also significantily lower in the minimally invasive subgroup (91.2% vs 97.1%, 93.8% vs 99.0%, respectively).
Study limitations. Criticisms of this trial are that noninferiority could not be declared; in addition, the investigators were unable to complete enrollment secondary to early enrollment termination after the data and safety monitoring board raised survival concerns.
Many argue that subgroup analyses suggest a lower risk of poor outcomes in patients with smaller tumors (<2 cm); however, it is critical to note that this study was not powered to detect these differences.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
The evidence is compelling and demonstrates potentially worse disease-related outcomes using MIRH when compared to traditional RAH with respect to cervical cancer recurrence, rates of death, and disease-free and overall survival. Several hypotheses have been proposed, and future research is needed to elucidate the differences in variables responsible for the outcomes demonstrated in these studies. Although there has been no ban on robot-assisted surgical devices or traditional minimally invasive techniques, the National Comprehensive Cancer Network has updated its recommendations to include careful counseling of patients who require a surgical approach for the management of early-stage cervical cancer.
The evidence is compelling and demonstrates potentially worse disease-related outcomes using MIRH when compared to traditional RAH with respect to cervical cancer recurrence, rates of death, and disease-free and overall survival. Several hypotheses have been proposed, and future research is needed to elucidate the differences in variables responsible for the outcomes demonstrated in these studies. Although there has been no ban on robot-assisted surgical devices or traditional minimally invasive techniques, the National Comprehensive Cancer Network has updated its recommendations to include careful counseling of patients who require a surgical approach for the management of early-stage cervical cancer.
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