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National Comprehensive Cancer Network

About NCCN

NCCN Flash Updates: NCCN Guidelines®, NCCN Compendium®, NCCN Radiation Therapy Compendium™, and NCCN Templates® Updated for Cervical Cancer

NCCN has published updates to the following NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) with NCCN Evidence Blocks™:

  • Basal Cell Skin Cancer, Version 1.2020
  • Merkel Cell Carcinoma, Version 1.2020
  • Squamous Cell Skin Cancer, Version 1.2020

NCCN has published updates to the NCCN Guidelines®, the NCCN Radiation Therapy Compendium™, and the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Cervical Cancer. These NCCN Guidelines are currently available as Version 1.2020.

  • Clinical Stage (CERV-1)
    • Revised to Incidental finding of invasive cancer at simple (extrafascial) hysterectomy. (Also for CERV-9)
  • Primary Treatment
    • Non-Fertility Sparing
      • Stage IB1, IB2 and Stage IIA1: Revised, Pelvic EBRT + brachytherapy (total point A dose: 80–85 Gy) ± concurrent platinum-containing chemotherapy. (CERV-4)
      • Stage IB3 and Stage IIA2: Revised, "Definitive pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy (total point A dose ≥85 Gy) category 1 for primary chemoradiation) (CERV-4)
      • Footnote q regarding systemic therapy revised: Concurrent platinum-containing chemotherapy with EBRT utilizes cisplatin as a single agent (or carboplatin if cisplatin intolerant) or cisplatin plus 5-fluorouracil. (CERV-4) (Also for CERV-5, CERV-6, CERV-7, CERV-8, CERV-9, and CERV-11)
      • Positive adenopathy by CT, MRI, and/or PET (FIGO 2018 Stage IIICr)
        • Distant metastases with biopsy confirmation as clinically indicated: Footnote w is new: Consider ablative therapy for 1–5 metastatic lesions (category 2B) if the primary has been controlled. (Palma D, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet 2019;393:2051-2058.) (CERV-7) (Also for CERV-8) 
  • Adjuvant Treatment (CERV-5)
    • Surgical Findings; Positive pelvic nodes and/or Positive surgical margin and/or Positive parametrium: "Imaging workup for metastatic disease" was added prior to adjuvant treatment.
  • Incidental finding of invasive cancer after simple (extrafascial) hysterectomy (CERV-9)
    • Treatment for positive margins, gross residual disease, positive imaging, or primary tumor characteristics meeting Sedlis criteria: The bifurcation of "Imaging negative for nodal disease" and "Imaging positive for nodal disease" was removed. Patients with positive nodes by imaging are now redirected to page CERV-7 (Positive adenopathy by CT, MRI, and/or PET [FIGO Stage IIICr]) 
  • Surveillance (CERV-10)
    • Second bullet revised: "Cervical/vaginal cytology screening annually as indicated..."
    • Third bullet revised: "Imaging as indicated based on symptoms or examination findings suspicious for recurrence Stage-dependent imaging for follow-up"
    • Footnote aa revised: "Regular cytology can be considered for detection of lower genital tract dysplasia and for immunocompromised patients, although its value in detection of recurrent cervical cancer is limited. The likelihood of picking up asymptomatic recurrences by cytology alone is low. 
  • Principles of Pathology (CERV-A)
    • Pathologic assessment for carcinoma
      • Sub-bullet revised: Consider MMR/MSI, or PD-L1, and/or NTRK gene fusion testing for patients with recurrent, progressive, or metastatic disease
      • The following footnotes are new:
        • According to the 2018 International Endocervical Adenocarcinoma Criteria and Classification (IECC), morphologic features (luminal mitotic figures and apoptosis) can be used to distinguish between human papillomavirus (HPV)-associated endocervical adenocarcinomas and non-HPV–associated adenocarcinomas. Tumors can be further subtyped based on morphologic features.
        • Evaluation of histologic pattern of invasion for endocervical adenocarcinomas is an emerging concept. Three clinically significant histologic patterns of invasion for endocervical adenocarcinoma have been described. Tumors with so-called pattern A invasion (defined by well-demarcated glands with round contours, an absence of single cells, an absence of desmoplastic stromal response, and no lymphatic vascular invasion) have excellent survival and do not have lymph node metastases or recurrences. (Diaz De Vivar A, Roma AA, Park KJ, et al. Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study. Int J Gynecol Pathol 2013;32:592-601.)
        • Footnote d revised: Ultrastaging commonly entails serial sectioning of the SLN and review of multiple H&E stained sections and with or without cytokeratin immunohistochemistry for all blocks of the SLN. There is not a standard protocol for lymph node ultrastaging.  
  • Principles of Imaging (CERV-B)
    • Initial Workup
      • Stage I 
        • Non-Fertility Sparing
          • Sub-bullet revised: Whole-body PET/CT (preferred) or chest/abdomen/pelvic CT or PET/MRI in FIGO stage IB3 ≥IB1.
          • Sub-bullet removed: Consider whole body PET/CT or chest/abdomen/pelvic CT in FIGO stage IB1–IB2. Recommendations were incorporated into another bullet.
        • Fertility Sparing
          • Sub-bullet revised: Consider Whole-body PET/CT (preferred) or chest/abdomen/pelvic CT in FIGO stage IB1–IB2.
      •  Revised staging: Stage II–IVA  
    • Follow-up/Surveillance: Imaging recommendations were added for Stage IVB or recurrence.
  • Principles of Evaluation and Surgical Staging (CERV-C)
    • Types of Resection and Appropriateness for Treatment of Cervical Cancer
      • Fourth bullet revised: "The standard and historical recommended approach for radical hysterectomy is with an open abdominal approach (category 1). Previous iterations of the guidelines indicated that radical hysterectomy could be performed via open laparotomy or minimally invasive surgery (MIS) laparoscopic approaches, using either conventional or robotic techniques. However, several key contemporary reports have questioned the presumed therapeutic equivalency of open vs. MIS approaches. A prospective randomized trial demonstrated..." 
    • Footnote c is new: In the phase III randomized FILM trial, indocyanine green (ICG) was shown to be non-inferior to isosulfan blue dye. (Frumovitz M, Plante M, Lee PS et al. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial. Lancet Oncol 2018;19:1394-1403).
    • Footnote g is new: There is no standard protocol for ultrastaging. Ultrastaging typically includes serial sectioning of the gross lymph node with review of H&E with or without cytokeratin IHC staining. See Principles of Pathology (CERV-A).
    • Table 1: Resection of Cervical Cancer as Primary Therapy
      • Surgical approach recommendations were revised as follows:
        • Comparison of Hysterectomy Types
          • Extrafascial Hysterectomy (Type A): Vaginal or laparotomy or minimally invasive
          • Modified Radical Hysterectomy (Type B): Laparotomy or minimally invasive
          • Radical Hysterectomy (Type C1): Laparotomy or minimally invasive
        • Comparison of Fertility-Sparing Trachelectomy Types
          • Radical Trachelectomy: Vaginal or laparotomy or minimally invasive (category 2B for MIS)
      • Footnote m is new: There is a lack of data on oncologic outcomes for minimally invasive surgical approaches to trachelectomy.
  • Principles of Radiation (CERV-D)
    • General Principles: Third bullet revised, Brachytherapy is a critical component of definitive therapy for all patients with primary cervical cancer who are not candidates for surgery. This is performed using an intracavitary ± and/or an interstitial approach.
    • Dosing Prescription Regimen - External Beam:
      • Bullet revised: "Coverage of microscopic nodal disease requires an EBRT dose of approximately 40–45 Gy (in conventional..."
    • Definitive Radiation Therapy for an Intact Cervix
      • Bullet revised: "...The primary cervical tumor is then boosted, using brachytherapy, with an additional 30 to 40 Gy using either image guidance (preferred) or to point A (in low dose-rate [LDR] equivalent dose), for a total point A dose (as recommended in the guidelines) of 80 Gy for small-volume cervical tumors or ≥85 Gy for larger-volume cervical tumors. For very small tumors (medically inoperable IA1 or IA2 EQD2 D90 doses of 75–80 Gy may be considered). Grossly involved unresected nodes may be evaluated for boosting with an additional 10 to 15 Gy of highly conformal (and reduced-volume) EBRT. With higher doses, especially of EBRT, When using image guidance for EBRT, care must be taken to exclude or severely limit the volume of normal tissue..."
    • Post-hysterectomy Adjuvant Radiation Therapy
      • Bullet revised: "...At a minimum, the following should be covered: upper 3 to 4 cm of the vaginal cuff, the parametria, and immediately adjacent nodal basins (such as the external and internal iliacs, obturator and presacral nodes). For documented nodal metastasis, the superior border of the radiation field should be appropriately increased (as previously described). A dose of 45 to 50 Gy in standard fractionation with IMRT is generally recommended..."
    • Dosing Prescription Regimen - Brachytherapy
      • Second bullet revised: "...The goals of care would include an equivalent dose at 2 Gy (EQD2) to the high-risk CTV (HR-CTV) with a D90 of ≥80 80–85 Gy; however, with large disease or poor response dose goals should be HR-CTV D90 ≥87 Gy..."
      • Third bullet revised: "...Clinicians using high dose-rate (HDR) brachytherapy would depend on the linear-quadratic model equation to convert nominal HDR dose to point A to a biologically equivalent LDR dose to point A (http://www.americanbrachytherapy.org/guidelines/). Multiple brachytherapy schemes have been used when combined with EBRT. However, one of the more common HDR approaches is 5 insertions with tandem and colpostats, each delivering 6 Gy nominal dose to point A. This scheme results in a nominal HDR point A dose of 30 Gy in 5 fractions..."
  • Systemic Therapy Regimens for Cervical Cancer
    • "Strongly consider clinical trial" was removed from the page title. This recommendation is listed in the guideline footer.
    • Chemoradiation
      • Other Recommended Regimens: Cisplatin/fluorouracil was removed as an option.
    • Recurrent or Metastatic Disease
      • First-line combination therapy
        • The following agents were moved from the list of Preferred Regimens and added to the list of Other Recommended Regimens:
          • Cisplatin/paclitaxel (category 1)
          • Carboplatin/paclitaxel (category 1 for patients who have received prior cisplatin therapy)
          • Topotecan/paclitaxel/bevacizumab (category 1)
          • Topotecan/paclitaxel 
      • Second-line therapy
        • Larotrectinib or entrectinib for NTRK gene fusion-positive tumors (category 2B) was listed as an option. It was preference stratified as "Useful in certain circumstances."
    • Footnote g is new: See NCCN Guidelines for the Management of Immunotherapy-Related Toxicities.

NCCN has published updates to the NCCN Templates® for Cervical Cancer to reflect the NCCN Guidelines for Cervical Cancer, Version 1.2020.

The following NCCN Template has been removed:

  • CRV18: CISplatin/Fluorouracil with Concurrent Radiation