Clinical Review

2019 Update on gynecologic cancer

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Gynecologic malignancies continue to be among the most deadly cancers for women. In this article: HIPEC, PARP, and minimally invasive hysterectomy.



Of the major developments in 2018 that changed practice in gynecologic oncology, we highlight 3 here.

First, a trial on the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with ovarian cancer after neoadjuvant chemotherapy demonstrated an overall survival benefit of 12 months for patients treated with HIPEC. Second, a trial on polyadenosine diphosphate-ribose polymerase (PARP) inhibitors as maintenance therapy after adjuvant chemotherapy showed that women with a BRCA mutation had a progression-free survival benefit of nearly 3 years. Third, the Laparoscopic Approach to Cervical Cancer trial revealed a significant decrease in survival in women with early-stage cervical cancer who underwent minimally invasive radical hysterectomy compared with those who had the traditional open approach. In addition, a retrospective study that analyzed information from large cancer databases showed that national survival rates decreased for patients with cervical cancer as the use of laparoscopic radical hysterectomy rose.

In this Update, we summarize the major findings of these trials, provide background on treatment strategies, and discuss how our practice as cancer specialists has changed in light of these studies' findings.

HIPEC improves overall survival in advanced ovarian cancer—by a lot

Van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378:230-240.

In the United States, women with advanced-stage ovarian cancer typically are treated with primary cytoreductive (debulking) surgery followed by platinum- and taxane-based chemotherapy. The goal of cytoreductive surgery is the resection of all grossly visible tumor. While associated with favorable oncologic outcomes, cytoreductive surgery also is accompanied by significant morbidity, and surgery is not always feasible.

Neoadjuvant chemotherapy (NACT) has emerged as an alternative treatment strategy to primary cytoreductive surgery. Women treated with NACT typically undergo 3 to 4 cycles of platinum- and taxane-based chemotherapy, receive interval cytoreduction, and then are treated with an additional 3 to 4 cycles of chemotherapy postoperatively. Several large, randomized controlled trials have demonstrated that survival is similar for women with advanced-stage ovarian cancer treated with either primary cytoreduction or NACT.1,2 Importantly, perioperative morbidity is substantially lower with NACT and the rate of complete tumor resection is improved. Use of NACT for ovarian cancer has increased substantially in recent years.3

Rationale for intraperitoneal chemotherapy

Intraperitoneal (IP) chemotherapy has long been utilized in the treatment of ovarian cancer.4 Given that the abdomen is the most common site of metastatic spread for ovarian cancer, there is a strong rationale for direct infusion of chemotherapy into the abdominal cavity. Several early trials showed that adjuvant IP chemotherapy improves survival compared with intravenous chemotherapy alone.5,6 Yet complete adoption of IP chemotherapy has been limited by evidence of moderately increased toxicities, such as pain, infections, and bowel obstructions, as well as IP catheter complications.5,7

Heated IP chemotherapy for recurrent ovarian cancer

More recently, interest has focused on HIPEC. In this approach, chemotherapy is heated to 42°C and administered into the abdominal cavity immediately after cytoreductive surgery; a temperature of 40°C to 41°C is maintained for total perfusion over a 90-minute period. The increased temperature induces apoptosis and protein degeneration, leading to greater penetration by the chemotherapy along peritoneal surfaces.8

For ovarian cancer, HIPEC has been explored in a number of small studies, predominately for women with recurrent disease.9 These studies demonstrated that HIPEC increased toxicities with gastrointestinal and renal complications but improved overall and disease-free survival.

HIPEC for primary treatment

Van Driel and colleagues explored the safety and efficacy of HIPEC for the primary treatment of ovarian cancer.10 In their multicenter trial, the authors sought to determine if there was a survival benefit with HIPEC in patients with stage III ovarian, fallopian tube, or peritoneal cancer treated with NACT. Eligible participants initially were treated with 3 cycles of chemotherapy with carboplatin and paclitaxel. Two-hundred forty-five patients who had a response or stable disease were then randomly assigned to undergo either interval cytoreductive surgery alone or surgery with HIPEC using cisplatin. Both groups received 3 additional cycles of carboplatin and paclitaxel after surgery.

Results. Treatment with HIPEC was associated with a 3.5-month improvement in recurrence-free survival compared with surgery alone (14.2 vs 10.7 months) and a 12-month improvement in overall survival (45.7 vs 33.9 months). After a median follow-up of 4.7 years, 62% of patients in the surgery group and 50% of the patients in the HIPEC group had died.

Adverse events. Rates of grade 3 and 4 adverse events were similar for both treatment arms (25% in the surgery group vs 27% in the HIPEC plus surgery group), and there was no significant difference in hospital length of stay (8 vs 10 days, which included a mandatory 1-night stay in the intensive care unit for HIPEC-treated patients).

For carefully selected women with advanced ovarian cancer treated with neoadjuvant chemotherapy, HIPEC at the time of interval cytoreductive surgery may improve survival by a year.

Continue to: PARP inhibitors extend survival in ovarian cancer...

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