Clinical Review

2019 Update on gynecologic cancer

OBG Manag. 2019 March;31(3):21, 22, 24-25, 26, 28

References

Vergote I, Trope CG, Amant F, et al; European Organization for Research and Treatment of Cancer–Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:943-953.
Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015;386:249-257.
Melamed A, Hinchcliff EM, Clemmer JT, et al. Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the United States. Gynecol Oncol. 2016;143:236-240.
Markman M. Intraperitoneal antineoplastic drug delivery: rationale and results. Lancet Oncol. 2003;4:277-283.
Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19:1001-1007.
Armstrong DK, Bundy B, Wenzel L, et al; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43.
Alberts DS, Liu PY, Hannigan EV, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335:1950-1955.
van de Vaart PJ, van der Vange N, Zoetmulder FA, et al. Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. Eur J Cancer. 1998;34:148-154.
Bakrin N, Cotte E, Golfier F, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients. Ann Surg Oncol. 2012;19:4052-4058.
van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018;378:230-240.
Burger RA, Brady MF, Bookman MA, et al; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473-2483.
Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917-921.
Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-2505.
Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30:695-700.
Clinical Outcomes of Surgical Therapy Study Group, Nelson H, Sargent DJ, et al. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med. 2004;350:2050-2059.
Lee EJ, Kang H, Kim DH. A comparative study of laparoscopic radical hysterectomy with radical abdominal hysterectomy for early-stage cervical cancer: a long-term follow-up study. Eur J Obstet Gynecol Reprod Biol. 2011;156:83-86.
Malzoni M, Tinelli R, Cosentino F, et al. Total laparoscopic radical hysterectomy versus abdominal radical hysterectomy with lymphadenectomy in patients with early cervical cancer: our experience. Ann Surg Oncol. 2009;16:1316-1323.
Nam JH, Park JY, Kim DY, et al. Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study. Ann Oncol. 2012;23:903-911.
Obermair A, Gebski V, Frumovitz M, et al. A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer. J Minim Invasive Gynecol. 2008;15:584-588.
Mendivil AA, Rettenmaier MA, Abaid LN, et al. Survival rate comparisons amongst cervical cancer patients treated with an open, robotic-assisted or laparoscopic radical hysterectomy: a five year experience. Surg Oncol. 2016;25:66-71.
National Comprehensive Care Network. NCCN clinical practice guidelines in oncology: cervical cancer, version 1.2018. http://oncolife.com.ua/doc/nccn/Cervical_Cancer.pdf. Accessed February 11, 2019.
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.

Is MIS radical hysterectomy (vs open) for cervical cancer safe?

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.

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.

For various procedures, minimally invasive surgery (MIS) is associated with decreased blood loss, shorter postoperative stay, and decreased postoperative complications and readmission rates. In oncology, MIS has demonstrated equivalent outcomes compared with open procedures for colorectal and endometrial cancers.^14,15

Increasing use of MIS in cervical cancer

For patients with cervical cancer, minimally invasive radical hysterectomy has more favorable perioperative outcomes, less morbidity, and decreased costs than open radical hysterectomy.^16-20 However, many of the studies used to justify these benefits were small, lacked adequate follow-up, and were not adequately powered to detect a true survival difference. Some trials compared contemporary MIS enrollees to historical open surgery controls, who may have had more advanced-stage disease and may have been treated with different adjuvant chemoradiation.

Despite these major limitations, minimally invasive radical hysterectomy became an acceptable—and often preferable—alternative to open radical hysterectomy for early-stage cervical cancer. This acceptance was written into National Comprehensive Cancer Network guidelines,²¹ and minimally invasive radical hysterectomy rapidly gained popularity, increasing from 1.8% in 2006 to 31% in 2010.²²

Randomized trial revealed surprising findings

Ramirez and colleagues recently published the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial, a randomized controlled trial that compared open with minimally invasive radical hysterectomy in women with stage IA1-IB1 cervical cancer.²³ The study was designed as a noninferiority trial in which researchers set a threshold of -7.2% for how much worse the survival of MIS patients could be compared with open surgery before MIS could be declared an inferior treatment. A total of 631 patients were enrolled at 33 centers worldwide. After an interim analysis demonstrated a safety signal in the MIS radical hysterectomy cohort, the study was closed before completion of enrollment.

Overall, 91% of patients randomly assigned to treatment had stage IB1 tumors. At the time of analysis, nearly 60% of enrollees had survival data at 4.5 years to provide adequate power for full analysis.

Results. Disease-free survival (the time from randomization to recurrence or death from cervical cancer) was 86.0% in the MIS group and 96.5% in the open hysterectomy group. At 4.5 years, 27 MIS patients had recurrent disease, compared with 7 patients who underwent abdominal radical hysterectomy. There were 14 cancer-related deaths in the MIS group, compared with 2 in the open group.

Three-year disease-free survival was 91.2% in the MIS group versus 97.1% in the abdominal radical hysterectomy group (hazard ratio, 3.74; 95% confidence interval, 1.63-8.58) The overall 3-year survival was 93.8% in the MIS group, compared with 99.0% in the open group.²³

Retrospective cohort study had similar results

Concurrent with publication of the LACC trial results, Melamed and colleagues published an observational study on the safety of MIS radical hysterectomy for early-stage cervical cancer.²² They used data from the National Cancer Database to examine 2,461 women with stage IA2-IB1 cervical cancer who underwent radical hysterectomy from 2010 to 2013. Approximately half of the women (49.8%) underwent minimally invasive radical hysterectomy.

Results. After a median follow-up of 45 months, the 4-year mortality rate was 9.1% among women who underwent MIS radical hysterectomy, compared with 5.3% for those who had an abdominal radical hysterectomy.

Using the complimentary Surveillance, Epidemiology, and End Results (SEER) registry dataset, the authors examined population-level trends in use of MIS radical hysterectomy and survival. From 2000 to 2006, when MIS radical hysterectomy was rarely utilized, 4-year survival for cervical cancer was relatively stable. After adoption of MIS radical hysterectomy in 2006, 4-year relative survival declined by 0.8% annually for cervical cancer (FIGURE).²²

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Both a randomized controlled trial and a large observational study demonstrated decreased survival for women with early-stage cervical cancer who underwent minimally invasive radical hysterectomy. Use of minimally invasive radical hysterectomy should be used with caution in women with early-stage cervical cancer.

References

Vergote I, Trope CG, Amant F, et al; European Organization for Research and Treatment of Cancer–Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:943-953.
Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015;386:249-257.
Melamed A, Hinchcliff EM, Clemmer JT, et al. Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the United States. Gynecol Oncol. 2016;143:236-240.
Markman M. Intraperitoneal antineoplastic drug delivery: rationale and results. Lancet Oncol. 2003;4:277-283.
Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19:1001-1007.
Armstrong DK, Bundy B, Wenzel L, et al; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43.
Alberts DS, Liu PY, Hannigan EV, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335:1950-1955.
van de Vaart PJ, van der Vange N, Zoetmulder FA, et al. Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. Eur J Cancer. 1998;34:148-154.
Bakrin N, Cotte E, Golfier F, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients. Ann Surg Oncol. 2012;19:4052-4058.
van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018;378:230-240.
Burger RA, Brady MF, Bookman MA, et al; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473-2483.
Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917-921.
Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-2505.
Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30:695-700.
Clinical Outcomes of Surgical Therapy Study Group, Nelson H, Sargent DJ, et al. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med. 2004;350:2050-2059.
Lee EJ, Kang H, Kim DH. A comparative study of laparoscopic radical hysterectomy with radical abdominal hysterectomy for early-stage cervical cancer: a long-term follow-up study. Eur J Obstet Gynecol Reprod Biol. 2011;156:83-86.
Malzoni M, Tinelli R, Cosentino F, et al. Total laparoscopic radical hysterectomy versus abdominal radical hysterectomy with lymphadenectomy in patients with early cervical cancer: our experience. Ann Surg Oncol. 2009;16:1316-1323.
Nam JH, Park JY, Kim DY, et al. Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study. Ann Oncol. 2012;23:903-911.
Obermair A, Gebski V, Frumovitz M, et al. A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer. J Minim Invasive Gynecol. 2008;15:584-588.
Mendivil AA, Rettenmaier MA, Abaid LN, et al. Survival rate comparisons amongst cervical cancer patients treated with an open, robotic-assisted or laparoscopic radical hysterectomy: a five year experience. Surg Oncol. 2016;25:66-71.
National Comprehensive Care Network. NCCN clinical practice guidelines in oncology: cervical cancer, version 1.2018. http://oncolife.com.ua/doc/nccn/Cervical_Cancer.pdf. Accessed February 11, 2019.
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.

2019 Update on gynecologic cancer

References

Is MIS radical hysterectomy (vs open) for cervical cancer safe?

Increasing use of MIS in cervical cancer

Randomized trial revealed surprising findings

Retrospective cohort study had similar results

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