Radiation therapy and surgery are widely recognized as effective treatments for cervical cancer. In recent years, chemotherapy has also been used for late-stage patients at home and abroad. Some people in China have researched the treatment of Chinese medicine, but they are in the groping stage, with poor effect, and can't be used as the means of radical treatment. In principle, stage I and IIa cases are mostly treated with surgery, while stage IIb and above should be treated with radiotherapy. Some authors believe that the use of several methods of integrated treatment, mainly radiotherapy and surgery, can improve the therapeutic effect. The method chosen for the first treatment of cervical cancer patients is the key to the therapeutic effect. It should be chosen appropriately according to the clinical stage of cervical cancer, pathologic type, patient's age, general health, as well as the conditions of therapeutic equipments and technical level.
I. Radiation therapy
Cervical cancer is moderately sensitive to radiation, which is applicable to patients of all stages, and it is the main treatment means for advanced patients. With the continuous improvement of radiation technology and accumulation of therapeutic experience, the cure rate has been gradually increased.
The principle of radiation therapy is to apply appropriate radiation dose, through reasonable layout, in order to achieve maximum elimination of tumor and protect normal tissues and organs as much as possible. The specific treatment plan should be carefully designed according to the patient's physique, clinical stage, local lesion size and the presence or absence of vaginal stenosis. Generally speaking, early cases are mainly treated with intracavitary radium therapy, and advanced patients focus on extracorporeal irradiation.
Radiation therapy for uterine cervical cancer mainly consists of two parts: intracavitary radiotherapy (60 drill or 137 cesium) and extracorporeal irradiation. The effective range of the former irradiation includes the cervix, uterine body, vagina and paracervical tissues ("A" point). The latter mainly targets the paracervical and pelvic wall tissues and the pelvic lymphatic region (point "B"). The two can cooperate with each other to achieve the purpose of eradicating cancerous tumors. In recent years, intracavitary irradiation with rear-loaded radioactive sources has been applied in foreign countries, and a few hospitals in China have begun to try it out, but the therapeutic effect and radiological complications have to be summarized continuously. At present, extracorporeal irradiation mostly replaces X-ray therapy with high-energy rays, and in addition to the long-range Υ-ray therapy machine (60-drill therapy machine), which has been commonly used in clinics, there are also electron-induced gas pedals and linear gas pedals that have begun to be used. Neutron beams and other high linear energy transfer rays (protons, etc.), is being studied in the trial.
The sensitivity of radiation has a certain relationship with the histopathologic type of cervical cancer. It is generally believed that adenocarcinoma is slightly less sensitive to radiation than squamous cell carcinoma, and it is advocated to adopt surgical treatment for adenocarcinoma as far as possible if the condition permits.
Surgery
is one of the main treatments for early cervical cancer. It is especially suitable for those who have no radiotherapy conditions and has better therapeutic effect. Most authors believe that, according to the degree, scope and clinical stage of the lesion and the patient's systemic condition, appropriate surgical procedures should be selected to minimize the surgical trauma and post-operative complications while striving for better therapeutic efficacy, so as to achieve the goal of neither blindly enlarging nor unprincipledly narrowing the scope of surgery. In principle, the indications for surgery are limited to stage 0～IIa, and radiotherapy is appropriate for those with obvious cancerous tumor erosion next to the cervix. Young patients can consider preserving the ovaries, while elderly patients over 65 years old, who are physically weak or accompanied by diseases of heart, liver, kidney and other organs are not suitable for surgical treatment.
(I) Surgical treatment of carcinoma in situ
Surgical methods include conization and total hysterectomy. Admittedly, a few carcinoma in situ of the cervix can be confined to the cervix, and the recurrence rate of conization is high. Although total hysterectomy also has recurrence, it is far better than conization, especially for those who need to remove the uterus for other indications. Some carcinoma in situ of the uterine cervix has multiple growths, even if extended total hysterectomy is performed, these lesions cannot be completely removed, so it is not necessary to perform it. If the preoperative lesions are found to be growing extensively in the vagina, surgery plus radiation therapy may be considered. The preferred treatment remains total hysterectomy, and conization should only be used in isolated cases where fertility preservation is required. Regardless of the treatment, patients should be followed for a long period of time. In addition to surgical resection, electrocautery, freezing and laser therapy can also be practiced.
(2) Surgery for early invasive carcinoma
The scope of surgery is not unanimous. In the past, many authors tended to perform extensive hysterectomy and pelvic lymphatic cleansing, which increased the complications and operative mortality rate, but after a long time of clinical practice, it was found that pelvic lymph nodes seldom metastasized. According to the statistics of 1118 cases of stage Ia cervical cancer at home and abroad, the rate of lymphatic metastasis was 0.8%, so it is advocated to reduce the scope of surgery appropriately. According to the depth of infiltration, scope of lesion, vascular space and lymphatic infiltration, degree of cell differentiation and patient's specific situation, appropriate operation should be adopted; Creasman et al. advocated that simple total hysterectomy should be performed for interstitial infiltration of less than 3mm; for infiltration of 3-5mm and fusion of foci of carcinoma, radical uterine curettage and pelvic lymph node dissection should be carried out; and when vascular infiltration occurs, radical surgery should be performed regardless of the depth of infiltration. In Tianjin Wang Zhaomin's opinion, if the depth of cancer infiltration is less than 5mm and the patient is young and requires fertility, cervical conization can be performed with regular follow-up; if the cancer infiltration is less than 5mm and there is carcinoma in situ in the upper part of the vagina, then total uterine resection or enlarged total hysterectomy with adequate vaginal wall excision should be performed; if the cancer infiltration is less than 5mm and there is tumor embolism in lymphatic ducts, then total uterine resection or enlarged total hysterectomy with the fornix portion of vagina should be performed and pelvic lymph node removal should be carried out. Pelvic lymph nodes should be removed. Treatment of early invasive carcinoma in Peking Union Medical College Hospital: (1) for suspected infiltration, beginning infiltration and infiltration <1mm, simple total hysterectomy and resection of 0.5-1cm of the vaginal wall; (2) for infiltration depth of 1.1-3mm, sub-extensive total hysterectomy (ureteral freeing, paracentesis of 2-3cm, resection of 2cm of the vaginal wall) without lymph node dissection; (3) for infiltration depth of 3.1-5mm, if the lesion is scattered and without vasculature, the infiltration depth of the infiltration is less than 5mm. If the lesions are scattered, without vascular infiltration, sub-extensive hysterectomy is also performed. If the cancer fuses, the vasculature has tumor embolism, and the cells are poorly differentiated, radical uterine curettage and pelvic lymph node dissection or radiotherapy are performed. Domestic and foreign literature reports that the 5-year survival rate of early invasive carcinoma treated by surgery is 95-100%. It shows that as long as the diagnosis can be made in time and appropriate surgical methods are adopted, satisfactory results will be achieved.
(3) Surgery for invasive cancer
For stage Ⅰb and Ⅱa cervical cancer, extensive hysterectomy and pelvic lymph node dissection are advocated both at home and abroad. Its specific scope includes: ① common lower iliac, internal and external iliac, occlusive foramen and deep inguinal lymphatic tissues; ② whole uterus and paracervical tissues, uterosacral ligament, main ligament, vesicocervical ligament, and vaginal paracervical tissues are resected at least 3cm; ③ part of vaginal wall. The length is up to 3cm under the fornix or 3cm away from under the cancer tumor; ④ Bilateral adnexa. patients with earlier cervical cancer under 40 years old can keep one side of ovary.
Since 1963, the Affiliated Hospital of Shandong Medical University has routinely performed extraperitoneal pelvic lymphatic drainage and intraperitoneal wide hysterectomy for patients with stage Ⅰb, Ⅱa, and a part of stage Ⅱb cervical cancers, exposing the surgical field well, and the operation is more convenient and thorough, which reduces the occurrence of postoperative complications.
Shanghai hospitals analyzed the clinical data of 1,417 cases of cervical invasive carcinoma through surgical treatment, and concluded that the scope of surgery should be decided according to the size of the lesion, the early and late disease and the specific situation of the patients, and roughly divided the scope of surgical resection into four categories: one type of surgery refers to general abdominal total hysterectomy, including resection of the vaginal fornix of 1 to 2 cm, which is applicable to in situ cancer and microfocal early infiltration; two types of surgery refers to General transabdominal total hysterectomy including removal of 2cm of paracervical tissue without pelvic lymph node removal. It is suitable for those whose cancer foci are invisible to the naked eye but biopsy confirms early invasive cancer; Type III surgery refers to general transabdominal total hysterectomy, including resection of more than 2cm of paracervical tissues and 2-3cm of vaginal fornix, and at the same time pelvic lymph node dissection, which is suitable for Stage I2 and Stage I3 (International Stage Ib in all cases); Type IV surgery refers to general abdominal total hysterectomy, including resection of more than 3cm of paracervical tissues along the side wall of the pelvis and removal of more than 3cm of vaginal fornix, which must be performed in Stages I2 and I3. The vault of the uterus is more than 3cm, and lymph node dissection must be performed at the same time. It is applicable to stage I4 and early stage II, i.e., stage Ib and stage IIa of the international staging.
Hubei Medical College proposes to classify the surgical methods for official neck cancer into six categories: total extrafascial hysterectomy, sub-extensive hysterectomy, sub-extensive hysterectomy and selective pelvic lymphadenectomy, extensive total hysterectomy and pelvic lymphatic drainage, extensive total hysterectomy and partial ureteral or/and partial cystectomy, and extended radical surgery. The aim is also to ensure the thoroughness and safety of the operation and to minimize complications. However, it is difficult to be so specific in practice. As for extended radical surgery or pelvic resection, it is mainly indicated for radiation failure and pelvic recurrence involving the bladder or rectum. However, the efficacy is poor and the complications and mortality rate are high, so it is only practiced in a few units. Transvaginal radical surgery for uterine cervical cancer has been changed to abdominal type due to the limitation of resection scope and improvement of conditions related to abdominal surgery. Due to the vigorous implementation of cancer prevention census in various regions, the number of early cervical cancer cases has been relatively increasing year by year, and the opportunities for surgical treatment have been increased accordingly. Especially in the current situation where radiotherapy equipment is not perfect and lack of treatment conditions in China, surgical treatment is still an important method to treat early cervical cancer.
(4) Radiotherapy before and after surgery
For patients with stage Ib (cauliflower type), stage IIa or above, if conditions are available, it is best to perform preoperative localized radium therapy or irradiation of vaginal body cavity tube. Its purpose is to shrink the local tumor, reduce the viability of the cancer tumor to avoid spreading during surgery as well as to reduce the chance of local recurrence. The radiation dose should be 1/2 of the full dose, and surgery is usually performed 4-6 weeks after the irradiation. Most authors advocate that where intraoperative paracervical metastasis is seen, lymphatic metastasis is seen on postoperative pathology, or cancerous tumors are still present at the margins of surgical resection, supplemental extracorporeal irradiation should be given one month after surgery, and the amount of pelvic tissues should be about 5000 rad. For those who have cancer in the vaginal breaks, supra-vaginal radium can be given for 3500-4000mg hours in 3-4 times.
Third, chemotherapy
At present, it is mainly used as a means of comprehensive treatment with poor efficacy, and is mostly used in palliative treatment or post-surgery adjuvant treatment for advanced cervical cancer. It can also be used with radiotherapy to increase the sensitivity of radiation and improve the curative effect.
There are dozens of commonly used chemotherapeutic drugs, but the clinical effects of cyclophosphamide and 5-fluorouracil are more certain. Bleomycin, adriamycin, and antitumor mustard also have higher remission rates. In addition, mitomycin (MMC), methotrexate, vincristine, hydroxyurea, tiotropium, azelaic acid phenylbutyrate, and melphalan (melphalan) have been shown to have varying degrees of efficacy.
The methods of drug administration are systemic drug, local drug and regional chemotherapy. Since the lesions of cervical cancer are mostly confined to the pelvis, some authors designed to infuse chemotherapeutic drugs into the major blood vessels supplying the tumor locally in order to increase the local drug concentration and enhance the efficacy.
Transsel used the internal iliac artery cannula to continuously instill methotrexate, and at the same time injected 5-formyltetrahydrofolate into the muscle to treat 15 cases of advanced cervical cancer, with an effective rate of 93.3%.
Hulka, Laufe et al. introduced the local chemotherapy of advanced cervical cancer through the internal iliac artery or the inferior gluteal artery, and also gained a certain therapeutic effect.
The Affiliated Cancer Hospital of Sun Yat-sen Medical College (1972) used the internal iliac artery cannula to instill nitrogen mustard, tiotepa and A-39 (cancer inhibitor) and other drugs combined with radium therapy to treat 29 cases of stage Ⅲ cervical cancer, and the 5-year survival rate was 65.3%, which was significantly higher than that of the radiotherapy group alone.
Shanghai Tumor Hospital has treated 55 cases of stage III cervical cancer with cyclophosphamide and radiotherapy, both at the same time, with daily or every other day static injection of 200mg of cyclophosphamide, the total amount of 5000mg or so, the survival rate of 5 years was 72.7%, which was significantly improved compared with that of the radiotherapy group alone (54.1%). In Guangdong Provincial People's Hospital (1979), chemotherapy was applied to 40 cases of advanced gynecological cancers by intubation of the arteries under the abdominal wall, together with surgery and radiotherapy, and received certain effect.
The Second Affiliated Hospital of Hunan Medical College (1981) treated 65 cases of stage Ib-III cervical cancer with sequential chemotherapy via cannulation of the artery under the abdominal wall, and the recent effective rate was 90.8%. The commonly used treatment program is nitrogen mustard 10mg once a day for three consecutive days, and then 5-fluorouracil 250-500mg once a day for seven consecutive days, 10 times for a course of treatment.
In recent years, Japanese author Hiraganeji reported the application of pelvic vascular bed isolation chemotherapy and single injection of MMC 60～80mg into internal iliac artery to deal with hemorrhage caused by advanced cervical cancer and pelvic recurrence of advanced cervical cancer after surgery or radiotherapy, and good results were obtained.
The Affiliated Hospital of Shandong Medical University (1982) applied pelvic vascular bed blockage and internal iliac artery infusion of cis-chloroaminoplatin, mitomycin C and cyclophosphamide to treat 13 cases of stage IIb to III cervical cancer. According to the evaluation index of chemotherapy effect formulated by the Second National Tumor Academic Conference, there were 11 cases with obvious effect and 2 cases with effective effect, and obvious local near-term effect was achieved. Nine of them underwent sub-extensive hysterectomy 40-58 days after blocking chemotherapy. Pathology confirmed local cancer tissue necrosis, tumor cell regression and inflammatory cell infiltration and other changes.
Recently, the use of bromocriptine in the treatment of advanced cervical cancer has been reported to have a significant effect in some patients.
Guthrie (1983) administered bromocriptine 2.5 mg orally to 18 patients with advanced cervical cancer three times a day. Among them, 5 cases (28%) tumor disappearance, 3 cases (17%) tumor inhibition, and that this drug long-term use of no side effects.
Fourth, traditional Chinese medicine
Therapy with traditional Chinese medicine can improve the general condition of the patients, enhance the immune function of the body, reduce the symptoms and prolong the life span, which is one of the measures for comprehensive treatment. In recent years, Chinese medicine treatment of early cervical cancer has shown some promising signs. Traditional Chinese medicine treatment is mainly based on local medication, supplemented by evidence-based treatment and internal Chinese medicine, and a number of single prescriptions and test prescriptions have also been adopted.
V. Immunotherapy
Immunotherapy for cervical cancer is still in the exploratory stage. At present, non-specific treatment is the mainstay, including BCG vaccine skin scratch, intratumor injection or oral intake; transfer factor subcutaneous or intramuscular injection; short rods bacillus subcutaneous or intravenous injection; immune ribonucleic acid intradermal injection and oral levamisole, etc. In addition, the preparation of tumor seedling can also be used, and the preparation of tumor seedling can also be used. In addition, tumor vaccine can also be prepared for autoinjection for active immunization. Immunotherapy is one of the auxiliary measures of comprehensive treatment, which helps to improve the survival rate of cervical cancer.
VI. Symptomatic treatment
(1) Emergency treatment of hemorrhage in cervical cancer Mostly seen in patients with advanced cervical cancer, often caused by cauliflower-type tissue necrosis and detachment, and also after sexual intercourse, gynecological examination or cervical biopsy. The bleeding can reach hundreds of ml in a moment, which puts the patient into shock and must be treated urgently. Simple and effective method is to quickly fill the vagina with sterile gauze or iodoform gauze compression hemostasis, may be appropriate to add hemostatic powder or gelatin sponge, etc., 24 ~ 48 hours to remove or re-replace the gauze. Can also be used in conjunction with the use of hemostatic drugs, such as blood, vitamin K, hemostatic cyclic acid, 6-aminohexanoic acid, anti-blood fibrinolytic aphrodisiac acid and so on. Patients should be instructed to rest in bed and given antibiotics to prevent infection. In hospitals with radiotherapy conditions, for patients with hemorrhage of cervical cancer, transvaginal radium can be used to stop hemorrhage in time (disappearing amount), and the effect is satisfactory. If the above treatments are ineffective, extraperitoneal ligation of internal iliac arteries on both sides can often control bleeding rapidly and effectively.Hiraoka(1976) reported that using pelvic vascular bed blockage and single injection of MMC 60-80mg into internal iliac arteries, the treatment of 4 cases of advanced cervical cancer with massive bleeding was successful. It was considered to be more satisfactory than simple ligation of the internal iliac artery for hemostasis.
(2) Handling of pain in advanced cervical cancer Pain can be caused by erosion or compression of nerves, blood vessels, ureter, fibrosis and adhesion caused by radiotherapy, infection of cancer tumor, obstruction of uterine pus and lymph node or bone metastasis, etc. Sometimes it is quite severe. Sometimes it is quite severe and the patient suffers a lot, so symptomatic treatment should be given. Generally, oral painkillers, such as Somycin, Meisan pain, Yuanhu painkillers or codeine, etc., are used first. Ineffective when switched to intramuscular injections, such as Zitazheng, strong pain, Anon pain or Chaihu injection, etc.. Strong analgesics, such as morphine, dulcolax, etc., have a good pain relieving effect, but are easily addicted and should not be applied for a long time. Some people use anesthesia ring pain method, that is, with 3 to 4 kinds of analgesic, sedative sequence of drugs to improve the effect of pain. For example, after luminal 0.1 oral, 10% chloral hydrate 15 ml anus, 1 hour after intramuscular injection of morphine 0.01 or dulcolax 50-100 mg. A simple and practical method of pain relief is the subdural alcohol injection, blocking the posterior root of the spinal cord sensory nerves. The puncture site is selected from 4 to 5 lumbar vertebral space, and a 20 to 23-gauge lumbar puncture needle is used. After the tip of the needle enters the sub-spidermal cavity, anhydrous alcohol or 95% alcohol 0.75 ml is injected, which must be pushed in slowly drop by drop, and it takes about 2 minutes to finish. Because the specific gravity of alcohol (0.806) is lower than that of spinal fluid (1.007), the alcohol quickly reaches the periphery of the posterior root. Cerebrospinal fluid should never be pumped into the syringe and mixed with alcohol before injection. After injection, the patient should be kept lying on the side for more than 1 hour, the side longer, the effect is better, and the patient can be allowed to get out of bed later. Alcohol may have temporary damage to the spinal cord, occasional incontinence, loss of sensation in the lower limbs, etc., which can be quickly recovered. This method is easier to operate, less expensive and has good pain relief effect, which may be adopted for patients with severe pain in advanced cervical cancer. However, the operation procedure must be strictly mastered.
VII. Recurrence of cervical cancer and its treatment
It is called recurrence when the symptoms and signs of cervical cancer disappear after treatment but the cancer tumor reappears after more than 6 months. If the cancer still exists within 6 months after treatment, it should be included as untreated.
(I) Time of recurrence Most of the recurrence of cervical cancer after radiotherapy occurs within 2 years. After recurrence of cervical cancer, if it fails to be treated, most of them will die within 6 months to 1 year, and only a few of them can survive for more than 2 years.
(2) Site of recurrence According to the literature, recurrence of cervical cancer is most common in the pelvic wall, parietal uterus and localized cervix. According to some statistics, the recurrence site after radiotherapy, the pelvic wall accounted for 15.4%, followed by localized foci of primary foci accounting for 8.2%, the lower part of vagina accounting for 1.7%, and distant metastasis accounting for 5.1%.
(3) Clinical characteristics vary according to the site of cancer recurrence. In localized cervical or vaginal recurrence, there is irregular vaginal bleeding or foul-smelling leukorrhea; in pelvic wall or parietal recurrence, there may be pain and swelling of lower limbs on the affected side, pain in lumbosacral region or lower abdomen, and parietal mass or fixed mass in sacral fossa can be detected in pelvic cavity; in rectal or bladder metastasis, there is blood in the stool or hematuria; bone metastasis often has localized pain; lung metastasis may have coughing, chest pain, and so on.
(4) Diagnosis When the above symptoms and signs appear after the treatment of cervical cancer, the possibility of recurrence should be thought of. For local recurrence in cervix and vagina, it is not difficult to confirm the diagnosis by cytological examination of vaginal smear and biopsy. However, recurrence in the parietal uterus and pelvic wall is mainly dependent on clinical symptoms and pelvic examination, which makes it difficult to confirm the diagnosis. Attention should be paid to the differentiation of pelvic masses from post-radical surgery lymphocysts, pelvic wall inflammatory masses, and paravaginal connective tissue fibrosis after radiotherapy. Local fine-needle aspiration for cell smear and pathologic examination can help to clarify the diagnosis, and B-mode ultrasonography, pyelogram, isotope nephrogram and CT pelvic examination have certain reference value for diagnosing recurrent cancer.
(5) Treatment The treatment of recurrent cancer is quite difficult and ineffective. Specific methods should be decided according to the site and scope of recurrence, the measures adopted in the initial treatment and the patient's general condition.
1. For recurrence of vaginal carcinoma in situ after surgery for cervical carcinoma in situ, local excision, partial vaginectomy or total vaginectomy and vaginal reconstruction are generally advocated. Freezing or laser can also be applied for local treatment. For elderly patients or patients who have had both ovaries surgically removed, vaginal radium therapy or X-ray vaginal cylinder irradiation is feasible.
2. For recurrence of invasive carcinoma after surgery, radiotherapy should be the main treatment, together with chemotherapy. For recurrent cancer of vaginal stump, intracavitary radium therapy and four-field vertical irradiation with 60 cobalt in vitro are feasible. After radiotherapy for post-surgical recurrent cancer, the 5-year cure rate is 15-20%.
3. The treatment of recurrence after radiotherapy for cervical cancer should be appropriate according to the site of recurrence, the first dose of radiotherapy, the time of the end of radiotherapy as well as the patient's general condition.
(1) For those who have recurrence within 2 years after receiving sufficient radiation, supplemental radiation therapy is generally not appropriate. If the recurrence is localized in the cervix, the upper part of the vagina, or the inner half of the uterine parietal, the use of surgical treatment has a certain effect, and most of the lesions can be excised, and radical surgery or pelvic organ removal is usually feasible. However, recurrences in the outer half of the paravaginal region and the pelvic wall can often not be removed surgically. Pelvic organ removal has many complications, high surgical mortality, and involves urinary and fecal diversion, with a low 5-year survival rate after surgery. Therefore, it is rarely used today.
(2) If the first radiotherapy dose is insufficient, and the cancer recurs in the pelvis or cervix within six months to two years after the end of radiotherapy, half-dose irradiation can be given again.
(3) For pelvic or cervical recurrent cancer more than 2 years after the end of radiotherapy, full-dose or reduced-dose radiation therapy can be considered again. Some people have applied local injection of isotope to paracervical recurrent cancer and obtained temporary remission.
4. For recurrent cancers that are not suitable for surgery or radiotherapy, chemotherapy or traditional Chinese medicine can be used.
5. If the recurrent cancer is found late and the patient is malignant, frozen pelvis or has distant metastasis, symptomatic treatment should be given to alleviate the pain. If patient's condition permits, palliative radiotherapy can be used for bone metastasis. 2000～3000 rad given for more than 2 weeks can reduce bone pain. For ureteral obstruction due to recurrent cancer or cancer causing urinary fistula, skin ureterostomy with continuous urine drainage can be considered as appropriate. Performing palliative urinary diversion is not helpful.