Treatment of Gynecological (Female-Specific) Cancers—Advances in 2017 and 2018

Gynecological (female reproductive tract) cancers are the fourth most common cancer group among women, but increasing cancer screening has reduced mortality risk. Looking at recent treatment advances:

1. Chemotherapy with Radiotherapy Is Sufficient for Locally Advanced Cervical Cancer (February 2018)

Surgery is the most appropriate treatment for early cervical cancer, considered suitable when confined to the cervix and smaller than 4 cm. For inoperable locally advanced cervical cancer, chemotherapy with radiotherapy is effective.

• Cervical Cancer Symptoms and Treatment by Stage (Detailed)

A study of surgery's role in locally advanced disease enrolled 635 cervical cancer patients. One group received chemotherapy and radiation, the other chemotherapy followed by surgery. After 5 years, disease-free survival was better with chemotherapy and radiotherapy alone, while overall survival was similar (1).

This confirmed our approach that concurrent chemotherapy and radiotherapy is the most appropriate treatment for locally advanced cervical cancer.

2. Heated Intraperitoneal Chemotherapy (HİPEK) Is Effective for Initially Inoperable Ovarian Cancer (January 2018)

Good surgery is the most important treatment for ovarian, fallopian tube and peritoneal cancers, common cancers of gynecological organs (ovaries, fallopian tubes, uterus, cervix and vagina). With widespread abdominal disease, initial chemotherapy followed by surgery is an option. The additional benefit of heated chemotherapy during surgery (Hyperthermic Intraperitoneal Chemotherapy, HIPEC) was investigated. More than 200 stage 3 ovarian cancer patients were enrolled. After 3 initial chemotherapy cycles and surgery, those receiving HIPEC during surgery had a 5-year disease-related mortality rate %10 lower and better disease-free survival (2).

Despite positive results, the major problem is the very small number of centers combining an experienced specialist HIPEC team with technical support.

• HİPEK Study Details

3. Fertility Preservation Is Possible in Selected Early-Stage Uterine Cancer Patients (December 2017)

Early detection and surgery produce high success rates in uterine (endometrial) cancer, but fertility loss from uterine removal is a major problem for young patients. The uterus has progesterone receptors . Studies have shown progesterone treatment to be effective. Comparing early uterine cancer patients receiving progestin with those undergoing surgery showed similar survival in stage 1A uterine cancer.

For young patients with stage 1A, low-grade uterine cancer, progesterone may be preferred over surgery to preserve fertility. We believe careful selection and close follow-up are essential.

• Uterine Cancer Stages and Treatment (Detailed)

4. Immunotherapy Drug Pembrolizumab (Ketyruda) Also Shows Efficacy in Pregnancy-Associated Gestational Trophoblastic Cancer (December 2017)

Gestational trophoblastic diseases are a rare group associated with pregnancy. Usually chemotherapy-sensitive, they very rarely develop resistance (%0.5 of patients). In this cancer, a protein important for immunotherapies , PD-L1, is present at over %90. Studies based on this showed that pembrolizumab, which releases immune-system brakes, is effective in chemotherapy-resistant gestational trophoblastic cancer.

5. Pembrolizumab Shows Efficacy in Recurrent or Metastatic Cervical Cancer (November 2017)

In recurrent or metastatic cervical cancer, options are limited. Adding targeted antiangiogenic (blood-vessel-inhibiting) bevacizumab to initial chemotherapy is a good option, but treatment for recurrence afterward is inadequate. A study of pembrolizumab (brand name Keytruda), which removes immune suppression, in this group evaluated patients with PD-L1, a biomarker , finding a benefit rate of %17 with pembrolizumab.

Pembrolizumab has entered clinical use in many cancers, including lung, malignant melanoma, renal cell, stomach and bowel cancer. As gynecological cancer studies increase, it appears likely to enter use there too.

6. Targeted Drug Bevacizumab with Chemotherapy Is Also Effective in Cervical Cancer (November 2017)

Improved screening allows early cervical cancer diagnosis. Vaccination developed against its cause, HPV infection , has made incidence very low in many European countries. In the vaccine's country of discovery, Australia, cervical cancer is close to complete elimination.

Approximately %15 of cervical cancers are metastatic at diagnosis, and chemotherapy options are limited. A study investigating bevacizumab (brand name Altuzan), a targeted drug reducing tumor blood supply, showed that adding it to chemotherapy provided an additional 4 months of overall survival.

Bevacizumab is now used with chemotherapy for cervical cancer that has spread throughout the body or recurred.

7. Olaparib Receives FDA Approval for Stage Four or Recurrent Ovarian Cancer Treatment (August 2017)

On 17 August 2017, the United States Food and Drug Administration, FDA, approved, for patients previously responding to platinum -containing chemotherapy completely or partially, olaparib (brand name Lynparza) tablets for maintenance treatment of recurrent ovarian, fallopian tube or peritoneal cancer. The BRCA gene is associated with DNA repair.

BRCA mutationresults in insufficient DNA repair, ultimately paving the way for cancer development. Hereditary BRCA mutations in ovarian cancer were the indication for olaparib's clinical introduction in 2014. In this new study, among ovarian cancer patients whose tumors did not contain these BRCA genetic changes, olaparib maintenance after chemotherapy prolonged time to recurrence 2-fold. Based on the study, the FDA approved olaparib maintenance for ovarian cancer.

8. Two Studies Affecting Postoperative Preventive Treatment Decisions in Uterine Cancer (June 2017)

The uterus has two layers: the inner layer is called the endometrium , while the outer muscle layer is the myometrium . Cancer arising from cells of the endometrial layer produces endometrial cancer , the most common female reproductive organ cancer. Uterine cancer usually refers to endometrial cancer.

Surgery is the initial treatment in early-diagnosed patients. For postoperative planning, a disease risk group is determined: low, intermediate or high.

High-risk patients: Serous or clear-cell type, extension to the cervix or vagina (birth canal), or spread beyond the uterus defines high-risk disease. No single preventive approach exists. Two studies in high-risk endometrial cancer patients sought to determine adjuvant (preventive) treatment:

The first assessed 660 postoperative high-risk endometrial cancer patients with no visible disease, asking whether both postoperative recurrence-reducing chemotherapy and radiotherapy were needed. Preventive radiotherapy alone was given to 330 patients and combined radiotherapy and chemotherapy to 330. Mean follow-up was 60 months. Five-year survival and time to recurrence did not differ, showing no added benefit from chemotherapy. Reassessment by stage showed the greatest benefit from combination treatment in stage III patients (an additional %11). In high-risk early-stage endometrial cancer, adding chemotherapy to radiotherapy offered no benefit.

The second investigated adding radiotherapy to chemotherapy for locally advanced endometrial cancer involving nearby lymph nodes but no distant organ metastases. Survival and time to recurrence did not differ between chemotherapy alone and concurrent chemotherapy-radiotherapy followed by chemotherapy. Distant recurrence was more frequent in the combination group, suggesting inadequate chemotherapy delivery in irradiated patients.

According to these two studies, when cancer remains confined to the uterus without extension or spread to neighboring organs, tumor characteristics permitting, radiotherapy alone may be given. When the tumor spreads within the abdomen, postoperative chemotherapy may be more effective, with no benefit from adding radiotherapy in this group.

• 10 Cancer Symptoms Women Should Know