Not a definitive trial
While the results of the LACC trial are concerning, it is not a definitive trial to end the practice of minimally invasive radical hysterectomy in all patients. The DFS and OS differences seen in the LACC trial were secondary endpoints and should be considered exploratory. Just as the US Food and Drug Administration requires two RCTs with a clearly defined primary endpoint for drug approval, we should hold surgical trials to similar standards, thus the LACC trial should prompt a call for another trial to be conducted in the United States or other countries with similar practice patterns with careful attention to oncologic principles and standardized postoperative therapy. Prior to the LACC trial, patient preference for MIS precluded adequate accrual, but the LACC data should rekindle an interest and make such a trial feasible.
An over-reaction to the available data
Moving completely away from minimally invasive radical hysterectomy without a definitive trial is an over-reaction to the available data. The current situation with MIS in cervical cancer is very similar to that in rectal cancer where two non-inferiority trials have been reported with inconclusive results.8,9 One of these trials was similar to the LACC trial in that the confidence interval for the primary endpoint did not include parity.9 However, as previously stated about this trial, “Failure to show non-inferiority cannot be used to imply inferiority.”10 It seems to be an over-reaction to use data from a single inconclusive trial as a basis for abandoning a procedure that has clear benefits. An unintended consequence of a move away from MIS is that it may decrease the availability of surgery for young patients with cervical cancer. Despite the advantages of surgery, only 9% of women with cervical cancer in the National Inpatient Sample Database from 2008 through 2015 were treated with radical hysterectomy.1 This likely reflects careful selection of patients for this surgery and suggests that the selection criteria for radical hysterectomy in the United States are particularly stringent, thus the patients treated with surgery here may not be similar to those in the LACC trial. In addition, it has been reported that patients having MIS have a higher body mass index and minimally invasive radical hysterectomy might be offered to patients who might not be candidates for an open radical hysterectomy due to technical challenges of open surgery in women who weigh > 100 Kg.
The LACC trial should be a call for caution and careful patient selection along with informed consent. This is a reasonable approach until we have more information. While we should inform our patients about the results of this trial when discussing surgery for cervical cancer, it is still reasonable to offer minimally invasive radical hysterectomy, especially to patients with tumors < 2 cm or who have tumors that can be removed prior to surgery.
The author reports no potential conflicts of interest with regard to this articl
- Piedimonte S, Czuzoj-Shulman N, Gotlieb W, Abenhaim Ha. Robotic radical hysterectomy for cervical cancer; a population-based study of adoption and immediate postoperative outcomes in the US. J Minim Invasive Gynecol. 2019; Mar-Apr;26(3):551-557.
- Monk BJ, Berman ML, Montz FJ. Adhesions after extensive gynecologic surgery: clinical significance, etiology, and prevention. Am J Obstet Gynecol. 1994;170:1396-403.
- Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med. 2018;379:1895-1904.
- Acuna SA, Dossa F, Baxter NN. Frequency of misinterpretation of inconclusive noninferiority trials: the case of the laparoscopic vs open resection for rectal cancer trials. JAMA Surg. 2019 Jan 1;154(1):90-92.
- Ong M. Conversation with The Cancer Letter. Ramirez: We no longer offer minimally invasive radical hysterectomy at MD Anderson. In: The Cancer Letter. Washington, DC; 2018.
- Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol. 1999;73: 177-183.
- Wang YZ, Deng L, Xu HC, Zhang Y, Liang ZQ. Laparoscopy versus laparotomy for the management of early stage cervical cancer. BMC Cancer. 2015;15:928.
- Fleshman J, Branda M, Sargent DJ, Boller AM, George V, Abbas M, et al. Effect of laparoscopic-assisted resection vs open resection of stage ii or iii rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial. JAMA. 2015;314:1346-1355.
- Stevenson AR, Solomon MJ, Lumley JW, Hewett P, Clouston AD, Gebski VJ, et al. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: The ALaCaRT randomized clinical trial. JAMA. 2015;314:1356-1363.
- Stevenson AR. The future for laparoscopic rectal cancer surgery. Br J Surg. 2017;104: 643-645.