Cite this as
Ismail MS, Ismail F, Ismail J, AlKhalifa M, Ismael R, et al. (2022) Development of a management guide wheel for cervical cancer. Ann Cytol Pathol 7(1): 014-028. DOI: 10.17352/acp.000025Copyright License
© 2022 Ismail MS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.We designed and developed a management guide wheel for cervical cancer to facilitate a standard approach and improve the quality of care in managing patients diagnosed with different stages of cervical cancer. Each step of the wheel considers the patient’s current medical condition, FIGO stage, and the possible treatment modalities for cervical cancer in her case. We reviewed existing international guidelines on the management of cervical cancer and compared their respective recommendations. This guide wheel is based on recommendations by the following organizations: the National Comprehensive Cancer Network (NCCN), the Society of Gynecologic Oncology (SGO), the European Society of Gynaecological Oncology (ESGO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), the British Gynaecological Cancer Society (BGCS) and the International Federation of Gynecology and Obstetrics (FIGO).
ASCO: American Society of Clinical Oncology; BGCS: British Gynaecological Cancer Society; CC: cervical cancer; CT: Computed Tomography; EBRT: External Beam Radiotherapy; ESGO: European Society of Gynaecological Oncology; ESMO: European Society for Medical Oncology; FIGO: International Federation of Gynecology and Obstetrics; IORT: Intra-Operative Radiotherapy; LN: Lymph Node; LND: Lymph Node Dissection; LVSI: Lymphovascular Space Invasion; MRI: Magnetic Resonance Imaging; NCCN: National Comprehensive Cancer Network; PET: Positron Emission Tomography; RH: Radical Hysterectomy; SGO: Society of Gynecologic Oncology; TNM: Tumors, Nodes, and Metastases.
Cervical Cancer (CC) is the fourth most common cancer in women worldwide and the second most common cancer in developing countries [1-7]. The mainstay of treating CC involves surgery, radiotherapy, chemotherapy, or a combination of those [6-9]. Early-stage CC is usually asymptomatic and patients present with symptoms in advanced stages [4,5,10]. CC can be preventable with effective screening and vaccination programs [4,5,11,12]. Early detection of pre-malignant states before they develop into cancer leads to earlier treatment and hence, a better outcome [12]. In fact, early-stage CC has a cure rate of 80-95% [8]. 30% of CC in developed countries are Stage IB or higher compared to 60% in developing countries due to the unavailability of well-established screening programs in the latter [2,12].
Various health organizations globally have developed sets of guidelines on the management of CC. We compared recommendations by the National Comprehensive Cancer Network (NCCN), the Society of Gynecology (SGO), the European Society of Gynaecological Oncology (ESGO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), the British Gynaecological Cancer Society (BGCS) and the International Federation of Gynecology and Obstetrics (FIGO) [4-6,9,10,13,14]. The NCCN guidelines for managing cancer cervix is one of the most frequently updated and comprehensive guidelines available [4].
We developed a management guide wheel for CC based on the recommendations of the compared guidelines but mainly reflecting the most recently updated guidelines by NCCN. This guide wheel aims to serve healthcare professionals in finding a quick and comprehensive display of the recommended steps and alternatives to manage patients diagnosed with CC when counseling patients. We are also comparing the guidelines covered here in another research article to highlight the similarities and differences in their respective recommendations. We developed a similar guide wheel for the management of uterine neoplasms [15]. We also developed a guide wheel describing the management of abnormal pap smear results and a comparison of the recommendations of international organizations [12,16].
This guide wheel includes recommendations and algorithms for managing patients with CC as per the guidelines compared during this study (Figure 1). It consists of a base (Figure 2) and an inner wheel (Figure 3). There is more information on how to use the guide wheel on the back of the base (Figure 4).
There are thirteen possible modalities of treatment with the different options under those modalities mentioned on the inner wheel as follows:
The guide wheel aligns the treatment modalities on the inner wheel with the particular stage of cervical cancer diagnosed, on the outer wheel, following clinical, radiological, and histopathological investigations. The viewing slot displays the steps recommended to follow in chronological order to manage the patient under consideration (Figure 1).
The base of the guide wheel displays color-coded treatment modalities in order. The numbers signify the steps and alternative options as follows:
1 → This marks the first option for Primary Therapy. It is a clearly defined recommendation.
1 → This is a second option for Primary Therapy. It might require greater clinical judgment and careful follow-up. If the clinical judgment is limited, either option 1 or 1 could be used.
2 → This marks the first option for Adjuvant Therapy.
3 → This is considered as a second option for Adjuvant Therapy and further treatment.
4 → This is usually reserved for surveillance.
5 → This is usually reserved for Relapse or Recurrence.
Abbreviations used on the wheel include the following:
The stages of cervical cancer shown on the outer wheel are as follows:
The back of the wheel displays the FIGO staging system for cervical cancer, most recently updated in 2018, as followed by the international guidelines. The table below exhibits the stages of cervical cancer and their definitions [1, 4, 6, 7, 9, 10].
Recommendations on managing patients with cervical cancer using the guide wheel
Sector 1: Fertility-Sparing Options for Stages IA1, IA2, IB1, and select IB2 Based on Cone Biopsy Results (Figure 5)
For patients with stage IA1 cervical cancer with negative margins and negative LVSI:
For patients with stage IA1 cervical cancer with positive margins and negative LVSI:
For patients with stage IA1 cervical cancer with positive LVSI and stage IA2 with negative margins:
For patients with stage IA2 cervical cancer with positive margins and stage IB1 with tumor measuring ≤ 2 cm:
For patients with stage IB1 with a tumor measuring > 2 cm and select cases of stage IB2 ≤ 2 cm:
Sector 2: Non-Fertility Sparing Options for Stages IA1, IA2, IB1, IB2, IB3, IIA1 and IIA2 Based on Cone Biopsy Results (Figure 6)
For patients with an inoperable stage IA1 cervical cancer with negative margins and negative LVSI:
For patients with an operable stage IA1 cervical cancer with negative margins and negative LVSI:
For patients with stage IA1 cervical cancer with margins positive for dysplasia or carcinoma but negative LVSI:
For patients with stage IA1 cervical cancer with positive LVSI and Stage IA2:
For patients with cervical cancer stages IB1, IB2, and IIA1:
For patients with cervical cancer stages IB3 and IIA2:
Sector 3: Primary Therapy for Stages IB3, IIA2, IIB, III, and IV Based on Imaging or Surgical Staging (Figure 7)
For patients with cervical cancer stages IB3, IIA2, IIB, III, and IV and negative adenopathy:
For patients with cervical cancer stages IB3, IIA2, IIB, III, and IV and positive adenopathy:
For patients with cervical cancer stages IB3, IIA2, IIB, III, and IV and negative surgical staging:
For patients with cervical cancer stages IB3, IIA2, IIB, III, and IV and positive surgical staging:
Sector 4: Adjuvant Therapy Based on Surgical Findings (Figure 8)
For patients with cervical cancer and negative nodes, margins, and parametrium, the adjuvant therapy is:
For patients with cervical cancer and positive pelvic nodes, margins, or parametrium, the adjuvant therapy involves:
For patients with cervical cancer and positive para-aortic nodes and negative distant metastasis, the adjuvant therapy involves:
For patients with cervical cancer and positive para-aortic nodes and positive distant metastasis, the adjuvant therapy involves:
Sector 5: Primary Therapy Based on Imaging Results Demonstrating Positive Adenopathy (Figure 9)
For patients with cervical cancer and positive pelvic LN but negative para-aortic LN based on imaging:
For patients with cervical cancer and positive pelvic LN and para-aortic LN based on imaging:
For patients with cervical cancer and positive adenopathy and distant metastases based on imaging:
Sector 6:Primary Therapy Based on Surgical Lymph Node Status (Stage IIICp) (Figure 10) For patients with stage IIIC1p cervical cancer with positive pelvic LN but negative para-aortic LN based on surgical LN status:
For patients with stage IIIC2p cervical cancer with positive para-aortic LN and negative distant metastasis based on surgical LN status:
For patients with cervical cancer with positive para-aortic LN and positive distant metastasis on imaging but not by biopsy:
For patients with Stage IIIC2p cervical cancer with positive para-aortic LN and positive distant metastasis on imaging and biopsy:
Sector 7: Incidental Surgical Finding of Cervical Cancer Post-Hysterectomy (Figure 11) For patients with an incidental finding of Stage IA1 cervical cancer with negative LVSI post-hysterectomy:
For patients with an incidental finding of stage IA1, IA2, or IB cervical cancer with positive LVSI but negative margins and negative imaging post-hysterectomy:
For patients with an incidental finding of Stage IA1, IA2, or IB cervical cancer with positive LVSI, margins, and imaging post-hysterectomy:
Sector 8: Stage IVB or Distant Metastases (Figure 12) For patients with stage IVB cervical cancer or distant metastases amenable to local treatment:
For patients with stage IVB cervical cancer or distant metastases not amenable to local treatment:
Sector 9: Surveillance of Persistent or Recurrent Disease (Figure 13) Surveillance of persistent or recurrent disease involves:
Sector 10: Therapy for Relapse (Figure 14) For patients with local/regional recurrence of cervical cancer with no prior RT:
For patients with central-local/regional recurrence of cervical cancer with prior RT:
For patients with non-central local/regional recurrence of cervical cancer and prior RT:
1b: Primary therapy is surgical treatment (1) with pelvic exenteration (f, g).
For patients with re-recurrence of cervical cancer:
A good staging system allows comparing outcomes of patients with similar characteristics within one center or across multiple centers [6]. Most guidelines including ASCO, BGCS, and NCCN use the FIGO 2018 classification for cervical cancer [1, 4, 6, 7, 9, 10, 17]. Before 2018, FIGO staged cervical cancer mainly based on clinical findings; however, in the recently updated staging system, pathological and imaging findings are taken into consideration [1,6,7]. Guidelines updated before 2018, such as ESGO and ESMO, rely on the Tumors, Nodes, and Metastases (TNM) staging due to this reason [5,13].
Patients with CC must be assessed with a thorough history and examination in addition to laboratory investigations and imaging studies [4,9,10,17,18]. Laboratory investigations include a complete blood count, liver and renal function tests [4,10,18]. Imaging includes chest x-ray, computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography/CT (PET/CT) [4,6,9,10,17-19]. MRI is superior to CT in detecting nodal disease but PET/CT is most sensitive [10,19-21]. Pre-operative PET/CT can help detect up to 54.8% of distant metastasis in CC [3].
Surgery is an option for early-stage CC. One option is conization and it aims to achieve negative margins [10,18,20,21]. Another option is hysterectomy, and there are three options: simple, modified radical, and radical [4,7]. Treating early-stage CC with RH and pelvic LND does not preserve fertility [17]. Fertility-sparing treatment is reserved for women with early-stage CC and good prognostic factors with no nodal disease [13,22]. It is not recommended for women with stage IB2 or IIA1 [10,18-20]. LVSI must be ruled out and the tumor has to measure 2 cm or less [10,18]. The presence of LVSI does not affect the staging of CC but it does affect treatment and the subsequent outcome [10]. Radical trachelectomy entails the resection of the cervix, part of the upper vagina, and the proximal parametria. It is ideally performed in the absence of LVSI, negative margins, and absent nodal disease [22]. Patients need to be counseled on the available treatment modalities and alternatives suitable for their individual case and their risks and benefits [10]. Neoadjuvant chemotherapy can help reduce the size of the tumor prior to surgery and can convert a non-fertility-sparing procedure into a more conservative approach [9,10,18,21].
Sentinel lymph node (SLN) biopsy involves removing the first-draining LNs. SLN biopsy has a high sensitivity in detecting metastasis in tumors measuring 2cm or less. It can be more reliable than LND to determine the nodal status [10]. Adjuvant therapy after surgery is indicated for patients with microscopic margins, nodal disease, and larger tumors [9,10]. It aims to reduce the risk of recurrence and increase the chance of cure [10]. Sedlis criteria can help determine those advised to receive adjuvant therapy as those with high risks including large tumor size, deep stromal invasion, and the presence of LVSI [4,5,7,10,13].
A total dose of radiotherapy administered should be 45-50 Gy [4,10,18,20,21]. Brachytherapy is a key component of RT, especially in patients with Stage IB1 or higher [2,19,20]. Treating women with advanced CC involves RT, including EBRT and BT, and platinum-based chemotherapy [10,20]. Recommended chemotherapy regimens usually include cisplatin with or without paclitaxel with or without bevacizumab [4,5,9,10,17,21]. Adding bevacizumab to the chemotherapy regimen is associated with improved overall survival, with more patients with a complete response without significantly reducing the quality of life [23].
Recurrence can either occur locally or distant and even both [7]. The most common site of recurrence is the pelvis [7,24]. The most common sites for distant metastasis include the lung, para-aortic LNs, and the abdominal cavity [8]. Treatment for recurrence depends on the primary therapy and the location of recurrence [9,10,14,18]. Unlike distant metastases, pelvic recurrences can be potentially cured with pelvic exenteration or radiation [5,8-10,19,21,24]. More than 90% of patients with distant metastasis will die within 5 years. Early-stage CC tends to metastasize locoregionally but can still metastasize to distant sites. Predictors of recurrence include tumor diameter, depth of stromal invasion, and the presence or absence of LVSI. If there is a high risk of recurrence after surgery, then post-operative adjuvant EBRT of the pelvis with or without chemotherapy with or without BT [8].
The aim of surveillance is to detect recurrent disease early when it can be effectively managed [8,13,14]. In a study by Gee et al., 13.7% of patients with locally advanced CC had “unsuspected distant metastases” [3]. The majority of recurrence occurs within 2-3 years after completing treatment and up to 95% of patients are symptomatic on presentation [10,14,18,24]. Follow-up is recommended every 3-4 months for the first two years after completing treatment and every 6-12 months for three more years and then annually or as deemed appropriate based on the patient’s individual risk of recurrence [4,5,9,10,13,14,19-21].
Managing patients with CC requires a multi-disciplinary team, which consists of a gynecologist, gynecologic oncologist, histopathologist, and radiologist, among others [10,13]. It is important to consider that not all patients have access to such services, especially in isolated settings and developing countries. We designed the guide wheel to reflect the recommendations for a highly resourced setting. This wheel is intended to facilitate the referral to established recommendations on managing patients with CC. It is not meant, in any way, to replace algorithms set by the guidelines mentioned. Although this guide wheel was designed during the COVID-19 pandemic, it does not offer any recommendations on changes in practice during this time.
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