Gynecologic Oncologist, Assistant Professor, Department of OB/GYN, Oregon Health & Science University, Portland

Dr. Moffitt reports no financial relationships relevant to this field of study.

SYNOPSIS: This paper is an epidemiologic validation of recent changes in cervical cancer staging.

SOURCE: Matsuo K, Machida H, Mandelbaum RS, et al. Validation of the 2018 FIGO cervical cancer staging system. Gynecol Oncol 2019;152:87-93.

The International Federation of Gynecology and Obstetrics (FIGO) recently revised the staging system for cervical cancer.¹ Matsuo et al validated the new staging system using the Surveillance, Epidemiology, and End Results (SEER) database.² Using Kaplan-Meier curves, they showed that cancer-specific survival for the new Stage IB subgroups were distinct from one another: Patients with Stage IB2 (tumor size 2-4 cm) were twice as likely to die of their disease as those with Stage IB1 (tumors < 2 cm with at least 5 mm depth of invasion). The new subgroups also had differences in clinical and histologic features. In addition, the authors showed that the cancer-specific survival outcomes for the new Stage IIIC1, which includes patients with pelvic lymph node metastasis, are more closely related to characteristics of the primary tumor than to the lymph node metastasis. For instance, Stage IIIC1 patients whose primary tumors were confined to the cervix had improved outcomes over the Stage IIIC1 patients whose tumors involved the parametria, vagina, or pelvic sidewall.

COMMENTARY

Until the recent update to the FIGO cervical cancer staging system, cervical cancer was staged based on clinical exam and a few allowable imaging studies that were easily accessible in low-resource settings. This was reasonable, as the vast majority of cervical cancer cases are located in developing countries. The staging did not account for pelvic or aortic lymph node metastasis since this was not identifiable clinically. Nonetheless, pelvic and aortic lymph node metastases have been known to be important prognostic factors.³ Thus, in developed countries, where CT scans, PET CTs, and surgical or radiology-guided biopsies are common, it is standard practice to assign a cancer stage using the 2014 FIGO clinical stage but annotate it with findings from imaging or pathology.

The 2018 FIGO cervical cancer staging system keeps the backbone of staging clinical, while incorporating results from imaging and pathology. The new staging adds Stage IIIC1 for pelvic lymph node metastasis and IIIC2 for aortic lymph node metastasis, similar to the FIGO staging of lymph nodes in endometrial cancer. The use of imaging, such as a PET CT, or pathology from a biopsy are necessary to assign either Stage IIIC1 or IIIC2. When imaging is used to identify pelvic or aortic lymph node metastasis, the patients are assigned as Stage IIIC1r or IIIC2r, respectively, with the “r” referring to radiology. Similarly, when a CT-guided biopsy or pathology from a lymphadenectomy is used to identify patients with pelvic or aortic lymph node metastasis, those patients are assigned Stage IIIC1p or IIIC2p, respectively, with the “p” indicating a pathology result.

Using retrospective data, Matsuo et al used the SEER database to show expected outcomes for each new stage. They highlighted the importance of splitting Stage IB from two subgroups to three subgroups, reflecting the improved outcomes for patients with tumors localized to the cervix with smaller (< 2 cm) tumors over those patients with larger (> 2 cm) tumors. The new 2018 FIGO staging also differentiates tumors < 2 cm in other important ways. For instance, fertility-sparing radical trachelectomy is best suited for patients with cervical tumors < 2 cm, per the National Comprehensive Cancer Network guidelines. Also, there is interest in allowing less radical surgery for patients with tumors < 2 cm with other low-risk tumor characteristics such as stromal invasion < 10 mm, no lympho-vascular space invasion, and squamous, adeno- or adenosquamous histology.⁴ This idea of offering less radical surgery to select early-stage cervical cancer patients is part of the impetus driving the development of the Querleu-Morrow classification for radical hysterectomy.⁵ This radical hysterectomy classification system describes a less-radical modified radical hysterectomy where the parametria are transected halfway between the cervix and the ureter.

In addition to the new FIGO staging system and its validation, surgical treatment of early-stage cervical cancer has changed substantially. Two recently published large studies showed poorer oncologic outcomes for patients with early-stage cervical cancer when treated with laparoscopy (with or without robotic assistance) compared with laparotomy.^6,7 Combining the randomized prospective data from Ramirez et al⁶ with the Melamed et al⁷ cohort study using the SEER database revealing essentially the same worsened outcomes for early-stage, potentially curable, cervical cancer patients, most gynecologic oncologists have moved back to a laparotomy. Even those with microscopic cervical malignancy now are counseled on the recent studies and are considered for a vaginal or laparotomy approach. Although it is unknown at this time exactly what aspects of laparoscopy and robotic surgery lead to increased recurrence and cervical cancer deaths in early-stage patients, some theories have evolved: use of the uterine manipulator disrupting the tumor and stimulating metastasis, and CO2 insufflation causing dispersion of tumor cells or influencing inflammation in a way that encourages metastasis.

Given the recent changes in cervical cancer staging and treatment, it is more important than ever when discussing cervical cancer with patients to be specific and detailed regarding findings on exam, radiology, and pathology and recommendations for treatment. I suggest stating the actual tumor size or the staging system used when discussing early cervical cancers. In addition, when surgical treatment for the patient is appropriate, clarity regarding surgical approach and extent of radicality are crucial. In particular, for the general gynecologist who occasionally performs a simple hysterectomy for patients with Stage IA1 cervical cancer, knowing the new FIGO 2018 staging system and counseling the patient on a nonlaparoscopic approach are prudent.

REFERENCES

1. Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynaecol Obstet 2018;143(Suppl 2):22-36.
2. Matsuo K, Machida H, Mandelbaum RS, et al. Validation of the 2018 FIGO cervical cancer staging system. Gynecol Oncol 2019;152:87-93.
3. Wagner AE, Pappas L, Ghia AJ, Gaffney DK. Impact of tumor size on survival in cancer of the cervix and validation of stage IIA1 and IIA2 subdivisions. Gynecol Oncol 2013;129:517-521.
4. Tseng JH, Aloisi A, Sonoda Y, et al. Less versus more radical surgery in stage IB1 cervical cancer: A population-based study of long-term survival. Gynecol Oncol 2018;150:44-49.
5. Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol 2008;9:297-303.
6. 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.
7. 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.