I. Definition of recurrent ovarian malignancy
Recurrent ovarian malignancy in a broad sense can be divided into two cases, i.e. recurrence and uncontrolled.
1.Recurrence (relapse): that is, after achieving complete clinical remission after treatment, the tumor reappears after six months.
2.Uncontrolled (failure of the treatment): that is, the tumor reappears within half a year after achieving complete clinical remission after treatment; or the tumor persists after treatment.
Signs and evidence of recurrence of ovarian malignancy:
1.Elevated tumor markers.
2.The appearance of thoracoabdominal fluid.
3.Masses found by physical examination.
4.Masses found on imaging.
5.The occurrence of unexplained intestinal obstruction.
If one of the above items exists, tumor recurrence can be considered; if two of the above items exist, tumor recurrence is more likely. The diagnosis of tumor recurrence is best supported by pathological examination report.
According to 2009 NCCN, persistent elevation of CA125 may not necessarily be a recurrence of ovarian cancer.
III. Overview of treatment of recurrence of ovarian malignancy
(A) Staging of recurrence and uncontrolled
Chemotherapy-sensitive type: the patient has achieved clinical remission with the initial platinum-based chemotherapy and has relapsed for more than 6 months after the planned cessation of chemotherapy.
2. Chemoresistant type: the patient achieved clinical remission with initial platinum-based chemotherapy, but relapsed within 6 months after stopping the planned chemotherapy.
3. Persistent ovarian malignancy: the patient has responded to the initial platinum-based chemotherapy or has responded significantly, but further examination reveals residual lesions, such as positive secondary exploratory surgery.
4. Refractory ovarian malignant tumors: ineffective for platinum-based chemotherapy. This includes tumor stabilization or tumor progression during initial chemotherapy. The incidence of this type is about 20%. It has the worst effective response rate to second-line chemotherapy drugs.
Surgical treatment of ovarian malignant tumors
(a) The purpose of surgery: (1) to remove or reduce the lesion; (2) to relieve the symptoms (intestinal obstruction).
(B) Types of surgery
(1) Re-dissection (relaparotomy):
(1) to clarify whether the recurrence, suspicious areas for biopsy.
(2) separation of adhesions, release of obstruction and intestinal rerouting, enterostomy.
2.recytoreductive surgery:
(1) complete or incomplete resection of recurrent foci.
(2) partial or complete resection of metastases or metastatic organs such as intestine, liver, spleen, lymph nodes and bladder.
(3) Principles of surgery selection
(1) Re-dissection:
Where the organs and tissues of the abdominal cavity are found to be diffusely recurrent and metastatic at the time of surgery (“twisted intestine”).
Metastases that are difficult to resect (hilar, pararenal vein, extra-abdominal metastases and multiple metastases in the liver parenchyma).
Massive ascites, intestinal obstruction that is difficult to relieve and extensive visceral adhesions and anatomical disorders. In this case, the aim of surgery is to explore, relieve symptoms and improve the quality of survival. If re-tumor cytoreductive surgery is performed, there are many postoperative complications, which are not beneficial to the patient.
2.re-neoplastic cytoreduction: If focal lesions with clear borders are found at the time of surgery, patients with recurrence more than >12 months after completion of first-line chemotherapy, good general condition or life status score, and young age (<50 years), it is estimated that ideal tumor cytoreduction can be accomplished. Under the above circumstances, re-operative tumor cytoreduction has fewer complications and can achieve the desired therapeutic purpose, which is beneficial to patients.
(D) Key points of surgery implementation
1. 5 abundants:
Adequate preoperative examination and assessment
Adequate understanding, knowledge and consent, informed benefits and risks, and the possibility of enterostomy.
Adequate bowel and blood source preparation
Adequate cardiopulmonary monitoring, general condition improvement and support
Adequate assistance from general surgery, urology, vascular surgery and other techniques.
2.The following procedures can be performed according to the situation:
(1) bowel resection and anastomosis, fistula (extensive disseminated intestinal metastases, ideal tumor cell reduction cannot be completed).
(2) Splenectomy (metastases or large metastases in the splenic flexure of the transverse colon).
(3) resection of liver metastases (single parenchymal metastases in the liver or large metastases in the transverse colon hepatic flexure)
(4) partial cystectomy and repair, ureteral transplantation and anastomosis, nephrectomy
(5) High lymph node dissection.
(E) Choice of surgical procedure
The initial treatment is:
(1) early-stage ovarian epithelial carcinoma: recurrence should be more actively considered for re-tumor cytoreductive surgery.
(2) Ovarian junctional tumor: because late recurrence and recurrence are mostly junctional tumors, they should be actively surgically removed.
(3) Malignant germ cell tumors of the ovary:
(1) surgery requiring preservation of reproductive function, the indications for which (e.g., one ovary and uterus are normal) are not limited by the gender of the initial operation period.
(2) Recurrence should be treated with surgery and chemotherapy.
(4) Interstitial tumor of the sex cord: those who can be operated should be operated again as far as possible.
V. Chemotherapy for ovarian malignant tumors
(1) Second-line chemotherapy regimen selection principles:
(1) Individualization: there is no standard chemotherapy regimen.
(2) The efficacy of initial chemotherapy can be used as a reference.
(3) The patient’s intention.
(2) Second-line chemotherapy drugs available Chemotherapy drugs:
(1) topotecan (trade name Hormexin).
(2) Paclitaxel.
(3) hexamethonium (HMM).
(4) Isocyclophosphamide (IFO).
(5) onychomycin (VP16).
(6) Tysodi (docetaxel).
(7) Gemcitabine (gemcitabine, trade name Jianze).
(8) liposomal adriamycin, etc.
(iii) Remedial treatment options for patients who fail platinum and vincristine therapy
1.Topotecan monotherapy: 1,25mg/m2 daily, intravenous drip, for 5d, with 3 weeks interval.
2.Hexamethonium monotherapy:Hexamethonium 260 mg/m2 per day for 14d with 2 weeks interval.
3.Isocyclophosphamide alone: Isocyclophosphamide 1.0~1.2g/m2 per day for 5d with an interval of 3 weeks. Isocyclophosphamide must be used in combination with mesna. Sodium mesna 400 mg/m2 per dose + NS 4ml per dose was administered intravenously at the same time as isocyclophosphamide and at the 4th and 8th hour afterwards.
4.Podophyllin monotherapy: 50 mg of podophyllin per day, orally, once a day for 21 d, 4 weeks as a course of treatment.
(D) Chemotherapy for different types of ovarian malignancies
In the development of second-line chemotherapy regimens, chemotherapy-resistant, persistent and refractory ovarian malignancies are often considered as a group, while platinum-sensitive recurrent ovarian malignancies are often considered separately.
(1) Treatment of chemotherapy-sensitive ovarian malignancies:
(1) The longer the duration of chemotherapy cessation, the greater the likelihood of remission with re-treatment, and the treatment of such patients should be aggressive.
(2) For isolated resectable lesions that have recurred for >12 months, surgical resection followed by chemotherapy can be considered; 2 courses of chemotherapy can also be considered before surgery, and chemotherapy can be continued after surgery.
(3) Chemotherapy can adopt the second-line chemotherapeutic drugs and programs that are clear and effective at present, or choose the program similar to the first-line chemotherapy program.
(2) Treatment of persistent ovarian malignancy: the choice of treatment plan depends on the previous chemotherapy regimen and the route of drug administration.
Treatment of drug-resistant and refractory ovarian malignancies:
(1) The main choice is to use the current more definite and effective second-line chemotherapeutic drugs and regimens.
(2) To give full consideration to the quality of survival of patients and the toxic side effects of drugs.
Other treatments for ovarian malignancies – radiotherapy
(1) Indications: It is mainly used for patients with advanced ovarian malignant tumor with local uncontrolled and single metastatic or recurrent lesions who are not suitable for surgery or chemotherapy resistance, in order to achieve the purpose of palliative treatment, prolong the life of patients and improve the quality of survival.
2. Contraindications:
(1) Extensive adhesions in the abdomen.
(2) Previous history of intestinal obstruction.
(3) Severe inflammation of the abdomen.
(4) inflammatory bowel disease.
In conclusion, the treatment of recurrent ovarian malignancies can be summarized in the following 3 points:
(1) The treatment of recurrent ovarian malignancies should be individualized and stratified.
(2) Chemotherapy-sensitive ovarian malignant tumors, especially those with long periods of tumor-free remission, have better efficacy when treated again, and should be treated actively in these patients.
(3) The treatment of recurrent ovarian malignant ovarian tumors is mostly palliative, and the quality of patient survival and the toxic side effects of various treatment regimens should be fully considered when formulating the treatment plan.
Peritoneal chemotherapy is used for the treatment of ovarian cancer, in principle, only for.
(1) microscopic lesions implanted on the surface of abdominal organs or peritoneal surface.
(2) Patients who have failed systemic chemotherapy, are drug resistant or have relapsed.
(3) Control of malignant ascites growth.
(4) Patients with positive second-look surgery.
Pre-emptive chemotherapy
Also known as neoadjuvant chemotherapy/downstaging chemotherapy, it was first applied to cervical cancer, and in recent years it has also been applied to ovarian cancer. It can give patients who originally did not have the chance of surgery the opportunity to have surgery and better treatment.
Advance chemotherapy is usually administered every 2 weeks, usually for 1 to 2 courses. More courses of upfront chemotherapy may induce the development of tumor resistance, which is not conducive to conventional chemotherapy after tumor cytoreductive surgery.
The value of prior chemotherapy is mainly that it can greatly improve the quality of surgery for tumor cytoreduction in ovarian cancer, but there is no evidence that it can prolong the survival time and improve the survival rate of patients. Therefore, prior chemotherapy is not always necessary for patients with early-stage ovarian cancer or those who are estimated to have no difficulty in undergoing surgery.
It is important to obtain a pathologic diagnosis of ovarian cancer before prior chemotherapy.