Discussion on issues related to cervical cancer surgery

  Cervical cancer has become the most important disease factor that threatens women’s life and health. The incidence rate of cervical cancer is second only to breast cancer and ranks second among female malignant tumors, with about 470,000 cases and 230,000 deaths per year worldwide, of which 80% are in developing countries. There are about 120,000 new cases and 60,000 deaths in China every year. With the development of cervical cancer prevention, the diagnosis rate of early cervical cancer is gradually increasing, and the incidence tends to be younger. Surgical treatment of cervical cancer is not only to improve the survival rate but also to improve the quality of survival. Surgery is mainly used as radical treatment for early-stage cervical cancer, surgical staging for advanced patients, and palliative treatment for recurrent patients. Throughout the history of surgical treatment of cervical cancer for more than 110 years, it has experienced the challenge and choice of whether surgery or radiotherapy is the main treatment and the reform and innovation from extended radical treatment to uterine function preservation, open surgery to minimally invasive surgery. The sword of surgery, as the most complete means to remove the primary foci and lymphatic drainage area of cervical cancer, conforms to the law of cervical cancer disease course development and is still the first choice for early stage cervical cancer treatment. However, in clinical practice, there are still some controversies in the surgical treatment of cervical cancer, which often confuse clinicians. Therefore, the following issues related to cervical cancer surgery are discussed.  According to the clinical staging method of the International Federation of Gynecology and Obstetrics (FIGO), all patients with stage I-IIA cervical cancer are indicated for surgery, while stage IIB or above are selected for radical radiotherapy, which has reached international consensus and is promoted as a guideline of the National Cancer Network (NCCN). The choice of surgery is based on clinical staging, which has subjective factors. Therefore, the FIGO clinical staging principles stipulate that when two clinical stages are available for the same patient, the earlier stage is chosen as the clinical stage. For example, when the same patient is clinically determined as IIA and IIB by two doctors, stage IIA should be selected as the clinical diagnosis. Current advances in imaging can compensate for the lack of clinical examination. preoperative MRI can determine the presence of parametrial infiltration and guide the choice of treatment modality. PET/CT has a sensitivity of 86% for lymph node metastasis, which is also valuable for treatment selection. Patients with ⅠB2 or ⅡA2, with a poor prognosis due to tumor diameter greater than 100px, can undergo direct radical surgery and decide whether to perform simultaneous radiotherapy after surgery according to risk factors.  For these patients with larger size, neoadjuvant chemotherapy is often used followed by surgery and postoperative adjuvant radiotherapy is available in domestic clinic. A prospective randomized clinical study at the Cancer Hospital of Fudan University showed that neoadjuvant radiotherapy, arterial interventional chemotherapy and intravenous chemotherapy resulted in tumor volume reduction, but no survival benefit was seen[1] . There is no high-level evidence that neoadjuvant chemotherapy can improve patient survival, and based on the principle of avoiding triple therapy as much as possible in the treatment of cervical cancer, most international oncology centers either operate directly or choose radical radiotherapy for patients with stage IB2 and IIA2.  II. Surgical scope for patients with different cervical cancer stages Since Weitherm performed the first extensive hysterectomy for cervical cancer in 1898, various surgical styles have emerged until 1974, when Piver et al. classified radical hysterectomy into 5 types to standardize the surgical scope and its indications. However, there are many drawbacks of Piver’s surgical classification, such as the excisional scope is too large, especially the vaginal resection is too long, and it cannot be applied to laparoscopic and nerve-preserving surgery.  International gynecologic oncologists have met several times to discuss new surgical staging for cervical cancer, and in 2008 Querleu et al [2] introduced a new surgical staging method based on three-dimensional anatomy, using radical hysterectomy with three-dimensional anatomy and the size of the lateral parametrial resection range as the only criterion for surgical staging, which was divided into the following four types: ① Type A: transection of parametrial tissue in the medial ureter, cervical The uterosacral ligament and uterine bladder ligament are removed in the proximal uterine segment; vaginal resection is usually within 25px without removing the parametrial tissue; the ureter is not freed, and its position and course are determined by direct vision or palpation. (ii) Type B: vertical ureteral tunnel excision of parametrial tissue; partial excision of the uterosacral ligament and uterine bladder ligament; excision of the vaginal cut edge at least 25px from the tumor; incision of the anterior sheath of the ureteral tunnel, exposure of the ureter, and lateral retraction. Type C: excision of parametrial tissue to the lateral ureter; pararectal dissection of the uterosacral ligament; parametrial dissection of the uterine bladder ligament; excision of the vaginal and parametrial tissues 1.5-2 cm from the tumor; complete freeing of the ureter. Type D: excision of parametrial tissue near the pelvic wall; complete excision of the uterosacral ligament and uterine bladder ligament; excision of the vagina according to the involvement of the lesion in the vagina, ensuring negative margins; and complete freeing of the ureter.  This new surgical staging has also been recognized by our colleagues[3] . It reflects the principle of individualized management according to the lesion. The staging based on anatomical structures can also be accurately described in laparoscopic or robotic surgery, and the new staging method covers new surgical concepts such as radical hysterectomy with preservation of the pelvic nerves. Reasonably narrowing the scope of surgery and preserving the function of the instrumental uterus are important tools to improve the quality of life of patients.  C. Radical hysterectomy with preservation of fertility function Cervical cytology screening is becoming increasingly popular, and its has greatly reduced the incidence of cervical cancer, but it has also led to an increase in the proportion of early-stage cervical cancer diagnosis. On the other hand, with the younger age of cervical cancer incidence and the delayed age of childbearing in modern society, the proportion of patients with incomplete childbearing in invasive cervical cancer is increasing year by year. While the traditional treatment is surgical removal of the uterus and regional lymph nodes, or radiation to kill the tumor in the primary site and lymphatic drainage area, surgery or radiation therapy will result in the loss of reproductive function of the patient while treating the tumor. This makes the preservation of reproductive function increasingly important in the treatment of cervical cancer. Radical tra-chelectomy (RT) was first performed by French surgeon Daniel in 1987. The scope of this procedure is almost similar to that of the classical radical hysterectomy in that only the diseased cervix is removed and the isthmus is anastomosed to the superior vagina, allowing the patient to cure the tumor while preserving fertility. Currently, the main types of radical hysterectomy are vaginal radical trachelectomy (VRT) and abdominal radical trachelecto-my (ART). ART is similar to open radical hysterectomy and is familiar to gynecologic oncologists and does not require special training; VRT, which is a femoral radical hysterectomy with laparoscopic pelvic lymph node dissection, requires a femoral hysterectomy technique and lumpectomy instruments. Current published data demonstrate that the oncologic safety of fertility-preserving RT is the same as that of radical hysterectomy, with a recurrence rate of 2% to 4% and a cumulative pregnancy rate of 50% to 60%. The main difference between the two standard procedures for selecting patients for RT is the tumor size, VRT is equivalent to B-type surgery, so the maximum tumor diameter is limited to 2 cm, while ART is equivalent to C-type surgery, which is relaxed to 100 px, and the rest of indications are similar.  Indications for ART at Fudan University Cancer Hospital: ①invasive cervical squamous carcinoma, adenocarcinoma and adenosquamous carcinoma; ②maximum tumor diameter less than 100px; ③FIGO stage IA2 to IB1, stage IA1 with vascular space involvement (LVSI); ④fertility desire; ⑤no clinical basis for infertility; ⑥no metastatic manifestation on chest X-ray; ⑦tumor located in the cervix without evidence of lymph node metastasis on MRI; ⑧age less than 45 years old; ⑧age less than 45 years old; ⑧tumor located in the cervix without evidence of lymph node metastasis on MRI. (8) age less than 45 years; (9) certain patients who are not amenable to negative surgery, such as adolescent cervical rhabdomyosarcoma [4]. The selection of the procedure is mainly based on the size of the patient’s tumor and the surgeon’s own technical conditions.  Whether patients with cervical cancer need lymph node dissection Lymph node metastasis is the main mode of metastasis in early cervical cancer. The site, number and extent of lymph node metastasis, clinical stage, pathological type and differentiation degree, surgery and adjuvant treatment are all important factors affecting the prognosis. The rate of pelvic lymph node metastasis in stage I Al patients is only 0.1% to 0.5%. If the patient is not accompanied by vascular infiltration, lymph node dissection is not required [5-6]; patients with stage I A2 or above require pelvic lymph node dissection or external pelvic lymph node irradiation; if lymph node biopsy confirms pelvic lymph node metastasis, simultaneous radiotherapy and chemotherapy to the pelvis should be given after surgery; among them, two or more pelvic lymph node metastasis, metastasis to the common iliac lymph nodes, or large pelvic lymph node metastasis should be given to the abdominal aorta extended field radiotherapy to the para-aortic lymph node area to reduce the possibility of residual para-aortic lymph node metastasis.  Pelvic lymph node metastasis is the earliest and the main metastatic route of cervical cancer, so the resection of pelvic lymph nodes should be complete. Generally, the scope of surgery is up to the middle section of the common iliac vein, down to the external iliac vein at the beginning of the deep iliac vein, outwardly from the medial genitofemoral nerve above the iliopsoas muscle, inwardly to the internal iliac artery and the atretic umbilical artery, and at the bottom to the closed nerve, in which the fatty lymph node tissue around the vessel is excised as a whole. In a summary of more than 500 patients, it was found that the rate of metastasis to the para-aortic lymph nodes in patients with stage I Bl to IA was as high as 5% to 19%. Analysis of risk factors for metastasis with para-aortic lymph nodes included stage IB1 cervical cancer tumors ≥3 cm, patients with stage IB2 to IIA, those with metastasis to the common iliac lymph nodes and those with enlarged lymph nodes detected by intraoperative exploration or preoperative imaging [7], while giving para-aortic lymph node dissection.