Cervical cancer

➡️Diagnostic and Staging Work up

·  Diagnostic and staging work up should include history and physical examination, complete blood count, as well as liver function and renal function studies.

➡️Good practice statement

· We recommend cervical cytology or Papanicolaou (Pap) smears and cervical biopsies for diagnosis.

➡️Strong recommendation, high grade evidence, (4).

· We recommend cone biopsy (i.e., conization) if the cervical biopsy is inadequate to define invasiveness or if accurate assessment of microinvasive disease is required.

➡️Strong recommendation, high grade evidence, (5).

· Recommended radiologic imaging includes pelvic MRI, and FDG-PET/CT

➡️Strong recommendation, high grade evidence, (6,7).

· Consider examination under anesthesia (EUA) cystoscopy/proctoscopy for cases having ≥ stage IB.

➡️Good practice statement

·  Consider options for fertility sparing

➡️ Conditional recommendation, high grade evidence, (8).

➡️Staging and risk assessment

· Tumor risk assessment should include tumor size, stage, depth of tumor invasion, lymph node status, LVSI and histological subtype.

➡️Strong recommendation, high grade evidence, (Table 4, appendix).

➡️Management of local/locoregional disease

➡️Surgery

·  Surgical therapy in cervical cancer should be adapted to the stage of disease according to FIGO and TNM classification (Appendix).

➡️Good practice statement

· Surgery should only be considered in patients with earlier stages of cervical cancer (up to FIGO IIA) without risk factors necessitating adjuvant therapy, which results in a multimodal therapy without improvement of survival but increased toxicity.

➡️Strong recommendation, high grade evidence (9).

· Microinvasive cervical cancer (stage IA1) without LVSI should be managed with conisation or simple trachelectomy to preserve fertility, and simple hysterectomy is recommended if the patient does not wish to preserve fertility.

➡️Strong recommendations, high grade evidence (8).

· In stage IA1 with LVSI, surgical assessment of pelvic lymph nodes is recommende

➡️Strong recommendation, moderate grade evidence (10).

· In patients with FIGO stage IA2, IB and IIA, radical hysterectomy with bilateral lymph node dissection (with or without SLN) is standard treatment, if the patient does not wish to preserve fertility.

➡️ Strong recommendation, high grade evidence, (9,11).

Adjuvant/neoadjuvant treatment

·  Consider NACT with surgery as this may reduce the need for adjuvant RT.

➡️Conditional recommendation, high grade evidence, (12,13).

· Intermediate-risk surgicopathologic findings, frequently referred to as Sedlis criteria, are defined by a combination of lymphovascular space involvement, depth of stromal invasion, and tumor size (Table 5, appendix), and they should be treated by whole pelvic RT delivered to a total dose of 4500 to 5040 cGy, in 180 Gy per fraction or 4000 to 4400 Gy in 200 Gy per fraction.

 ➡️Strong recommendation, strong grade evidence, (14-16).

·  Adjuvant CRT is recommended in high-risk patients (one or more negative prognostic factors such as positive or close surgical margins, positive lymph nodes or microscopic parametrial involvement). For these patients, whole pelvic RT should be delivered to a total dose of 4500 to 5040 cGy, in   180 cGy fractions, with concurrent weekly cisplatin (40mg/m2).

➡️ Strong recommendation, high grade evidence, (14,17).

Chemoradiotherapy in locally advanced cervical cancer

· We recommend CRT  for patients with bulky IB2–IVA disease, and the most commonly used regimen is weekly cisplatin 40 mg/m2;

➡️ Strong recommendation, high grade evidence, (18-23).

· Patients not eligible to cisplatin may receive carboplatin or gemcitabine.

 ➡️Strong recommendation, very low grade evidence (24,25).

· Brachytherapy is needed to obtain a sufficiently high dose to ensure a high rate of local control in advanced cases.

➡️Good practice statement

Management of advanced/metastatic disease

· Palliative chemotherapy with the aim of relieving symptoms and improving quality of life is recommended if the patient has a PS< 2 and no formal contraindications.

➡️Strong recommendation, high grade evidence, (26,27).

· Cisplatin-based doublets with paclitaxel or topotecan have demonstrated superiority to cisplatin monotherapy and should be used.

➡️Strong recommendation, high grade evidence (26,27).

·  Paclitaxel and cisplatin combined with bevacizumab is recommended as the preferred first-line regimen in metastatic or recurrent cervical cancer based on the balance between efficacy and toxicity profile.

➡️ Strong recommendation, high grade evidence, (28-30).

· The combination of paclitaxel and carboplatin is recommended as an alternative for patients that are not candidates for cisplatin.

➡️Strong recommendation, moderate grade evidence, (31).

 ➡️Strong recommendation, moderate grade evidence, (32).

· Some patients develop small lung metastases only, which do not rapidly progress and can be managed with stereotactic RT and/or a watchful waiting policy, frequently delaying systemic chemotherapy for a significant period of time.

➡️Conditional recommendation, low grade evidence, (33).

Local recurrence of cervical cancer following radical surger

· Higher doses of RT can be delivered with brachytherapy and increase the likelihood of local control for patients with small volume central recurrences.

➡️Strong recommendation, high grade evidence (34).

➡️Clinical indicators

· Follow-up visits with a complete physical examination including a pelvic–rectal exam and a patient history should be conducted by a physician experienced in the surveillance of cancer patients.

➡️Good practice statement

· CT or PET/CT scan should be carried out as clinically indicated. A reasonable follow-up schedule involves follow-up visits every 3–6 months in the first 2 years and every 6–12 months in years 3–5.

➡️Good practice statement

· Patients should return to annual population-based general physical and pelvic examinations after 5 years of recurrence-free follow-up.

➡️Good practice statement