Gold standard for surgical treatment of ovarian cancer. A new effective treatment for ovarian cancer has emerged. Ovarian cancer treatment
The treatment of malignant tumors continues to be a daunting task and remains the cornerstone of modern oncology. The development of science and the emergence of new methods of fighting cancer make it possible to achieve a complete recovery for many patients, but the main principle of treatment remains unchanged - maximum removal of tumor tissue. The role of surgery in cancer cannot be overestimated, because this is the only way to get rid of both the tumor itself and the negative impact it has on the affected organ. If the disease is detected at an advanced stage, then surgical intervention can, if not prolong the patient’s life, then at least improve his well-being and relieve him from the painful manifestations of cancer that poison the patient’s existence in the last months and weeks of life.
Removing various formations on the human body is not new in medicine; operations were performed thousands of years ago, and attempts to treat cancer were made even before our era. In Ancient Egypt, they tried to surgically remove breast tumors, but the lack of knowledge about the nature of tumor growth, the possibilities of anesthesia, antibiotic therapy, and the low level of antiseptic measures did not allow achieving positive results, so the outcome was quite sad.
The last century was a turning point that allowed us to reconsider our views on surgery in oncology. Improving approaches and re-evaluating existing standards made it possible to make surgical treatment not only more effective, but also rational when radical and often crippling interventions have been replaced by more gentle methods, allowing to prolong the patient’s life and maintain its quality at an acceptable level.
For many types of tumors, surgical removal has been and remains the “gold standard” of treatment, and most of us certainly associate the fight against a malignant tumor with the need for surgery. Chemotherapy and radiation, carried out both before and after cancer removal, have made it possible to significantly increase the effectiveness of surgical treatment, but there is nothing to completely replace surgery even in the 21st century.
Today, surgery in oncology is not limited only to the removal of a tumor; it also plays a diagnostic role, allowing one to accurately determine the stage of a malignant tumor, and when performing operations to remove entire organs, reconstructive surgery becomes one of the most important stages of both treatment and subsequent rehabilitation. If the patient’s condition is such that radical treatment is no longer possible, since there are severe concomitant diseases that prevent intervention, or time has been lost and the tumor has actively spread throughout the body, palliative operations come to the rescue, alleviating the condition and helping to avoid other complications from the tumor .
Approaches to cancer surgery
They are used in oncology and have much in common in the majority of patients with a specific type of cancer, and the differences in each patient are only in the list of drugs, their dosage, intensity and method of irradiation. Speaking of surgery, it is impossible to name any treatment regimen used for all patients with this type of cancer.
Choice of access, type of operation, its volume, need for organ reconstruction, number of stages of treatment, etc. almost always individual, especially in common forms of cancer. Of course, there are still certain standards in surgical treatment, but just as there cannot be two completely identical tumors, there are no exactly identical operations.
The most important condition for effective surgical intervention in oncological pathology is adherence to the principles of ablastics and antiblastics, which must be reproduced regardless of the type of cancer, form of growth, or condition of the patient.
Ablastika involves the total removal of the tumor within healthy tissue so that not a single cancer cell remains in the growth zone of the tumor. Compliance with this principle is possible with the so-called cancer in situ, which does not extend beyond the cellular layer that gave rise to cancer, in the first and second stages of the disease in the absence of cancer. The third and fourth stages of the tumor exclude the possibility of ablastic intervention, since cancer cells have already begun to spread throughout the body.
Antiblastics consists of certain measures that prevent further spread of the tumor after surgery. Since the removal of cancer may be accompanied by injury to tumor tissue, the risk of detachment of already poorly interconnected malignant cells and their entry into the vessels is quite high. Compliance with certain technical features during the process of tumor removal allows the surgeon to remove the tumor as carefully as possible, reducing the likelihood of recurrence and metastasis to a minimum.
TO Features of surgery for malignant tumors include:
- Careful isolation of the wound from tumor tissue, early ligation of blood vessels, especially veins, preventing the spread of cancer cells and metastasis.
- Change of linen, gloves, instruments at each stage of the operation.
- The advantage of using an electric knife, laser, cryotherapy.
- Rinsing the intervention area with substances with a cytotoxic effect.
Types of surgical operations in oncology
Depending on the stage of the tumor, its location, the presence of complications, and concomitant pathologies, the oncologist-surgeon gives preference to one type of operation or another.
When potentially dangerous neoplasms are detected that have a high risk of malignancy, the so-called preventive operations. For example, removal of colon polyps helps to avoid the growth of a malignant tumor in the future, and the patient is under constant dynamic monitoring.
The development of cytogenetic techniques has made it possible to identify gene mutations characteristic of certain neoplasms. This connection can be seen especially clearly for women, when in one family one can observe a recurrence of the disease in women from generation to generation. If a corresponding mutation is detected, you can resort to removing the mammary glands without waiting for the tumor to begin to grow. Such examples already exist and are known to many: actress Angelina Jolie underwent a mastectomy to avoid cancer in the future, because she was discovered to have a mutant gene.
Diagnostic operations are carried out to clarify the stage of the disease, the type of malignant neoplasm, the nature of the damage to surrounding tissues. Such interventions are necessarily accompanied by the removal of a tumor fragment for histological examination (biopsy). If all neoplasia is removed, then two goals are achieved at once - diagnosis and treatment. Diagnostic operations also include laparoscopy (examination of the abdominal cavity), laparotomy (opening the abdominal cavity for examination), thoracoscopy (examination of the chest cavity).
In recent years, thanks to the development of non-invasive, high-precision diagnostic methods that do not require surgical manipulation, the number of diagnostic operations to determine the stage of the oncological process has decreased significantly, although a decade ago this was common practice for some types of tumors.
Cytoreductive surgeries pursue the goal of getting rid of tumor tissue as much as possible and require mandatory subsequent chemotherapy or radiation. For example, ovarian cancer, often accompanied by tumor spread to nearby organs and peritoneum, is not always possible to remove completely, no matter how radical the operation.
Palliative interventions are carried out not with the goal of completely removing the tumor, but to alleviate the patient’s suffering or combat complications. Palliative care is often the responsibility of patients with advanced forms of cancer, when the tumor cannot be completely removed or radical intervention is associated with high risks. An example of such operations is the restoration of intestinal patency in inoperable cancer, stopping bleeding from a tumor, as well as the removal of single distant metastases. Another effect of palliative operations will be a reduction in tumor intoxication and some general improvement in the patient’s condition, which will allow additional courses of chemotherapy or radiation.
example of extensive surgery for pancreatic cancer with reconstruction of organ function
Reconstructive surgeries used to restore the function or appearance of an organ. If in the case of tumors of the intestines or urinary system, it is important for the patient to be given the opportunity to recover in the usual way by recreating either a section of the intestine, then after breast removal or facial surgery, the cosmetic effect is also an important aspect. Plastic surgery allows you to restore the external appearance of an organ, giving the patient the opportunity to live comfortably both in the family among relatives and outside it. The use of modern techniques and artificial materials for plastic surgery of parts of the body largely determines the success of reconstructive surgery.
Depending on the scale of the tumor lesion, the surgeon may resort to resection(partial organ removal), amputation(removal of an organ section) or extirpation(total organ removal). For small tumors and cancer in situ, preference is given to resection or amputation. The possibility of resection in case of damage to organs that produce hormones plays an important role. For example, such a gentle technique in the case of small tumors without metastasis gives a chance to at least partially preserve the function of the organ and avoid serious complications. Extensive tumor lesions leave no choice and require total removal of the organ along with the tumor.
Since a feature of a malignant tumor that distinguishes it from other pathological processes is metastasis, during surgical treatment of cancer it is customary to remove lymph nodes in which cancer cells can be detected. Germination of neighboring organs or tissues requires extensive operations in order to eliminate all visible foci of tumor growth.
From general to specific
Having described the general features and approaches to surgical treatment of oncological diseases, we will try to consider the features of operations for specific types of cancer. As mentioned above, the doctor always takes an individual approach to choosing the method of tumor removal, which depends on both the form of cancer and the organ in which it formed.
Breast cancer
It is considered one of the most common in women all over the world, so issues of not only treatment, but also subsequent rehabilitation and life concern many. The very first descriptions of radical surgery were made more than a hundred years ago, when the doctor William Halstead performed mastectomy about cancer. Halstead's operation was highly traumatic, as it required removal of the gland itself and fatty tissue, both pectoral muscles and lymph nodes. This volume of intervention crippled the patients, leading not only to a serious cosmetic defect, but also to deformation of the chest wall, which inevitably affected the function of the chest organs and the psychological state of the woman.
Throughout the 20th century, approaches to surgery for breast cancer have been improved, and accumulated experience has shown that the effect of more gentle methods is no worse, but the quality of life is higher, and the rehabilitation process is more successful.
Today, modified versions of the Halstead operation (with preservation of the pectoral muscles) are performed for stages 3-4 of the tumor with massive damage to the lymph nodes, and the radical mastectomy– only when neoplasia grows into the pectoralis major muscle.
The advantage of organ-preserving operations is the removal of only part of the organ, which gives a good cosmetic effect, but the condition for their implementation is early diagnosis.
For non-invasive forms of breast cancer, when there are no metastases either, it is performed removal of a sector or quadrant of an organ. The point of preserving the axillary lymph nodes is to not needlessly disrupt the lymphatic drainage of the arm, to avoid severe swelling, pain, and impaired movement that always accompany lymphadenectomy.
With invasive cancer, there is no choice, since the lymph nodes are often already involved in the pathological process and must be removed.
types of surgeries for breast cancer
For small tumors in stages I-II of the disease, one of the best operations is considered lumpectomy– removal of the tumor with surrounding tissue, but preserving the remaining part of the organ. Lymph nodes are removed through a separate small incision in the armpit. The operation is non-traumatic and “elegant”, has a good aesthetic effect, and the number of relapses or the likelihood of progression is no higher than with more extensive interventions.
The need to remove the entire gland, but without tissue and lymph nodes, may arise with non-invasive carcinomas and hereditary forms of the disease ( prophylactic mastectomy).
The appearance of the mammary gland after surgical treatment is of great importance, so the role of plastic surgery is great, allowing you to restore the shape of the organ both using your own tissues and using artificial materials. There are a great many options for such oncoplastic interventions, and the specifics of their implementation are dictated by the characteristics of the tumor, the shape of the mammary glands, the properties of the tissues, and even the surgeon’s preferences in choosing one or another tactic.
When choosing a specific method of surgical treatment, it is important to carefully examine the patient, assess all the risks and choose the operation that will meet all oncological criteria and will avoid recurrence and progression of the disease.
Prostate cancer
Along with breast tumors in women, in men it is also not losing ground, and the issues of surgery in this case are still relevant. The “gold standard” for cancer of this localization is considered to be total removal of the prostate– radical prostatectomy, there is nothing better or more effective than it, and the differences lie in the access and use of techniques that allow preserving nerves and erectile function. One option is laparoscopic prostatectomy, in which the organ is removed through a small incision, but this is only possible in the early stages of the tumor.
Foreign clinics and large Russian oncology hospitals equipped with modern equipment offer removal of the prostate using the robot-assisted Da Vinci system, which allows the intervention to be performed with even smaller incisions than with laparoscopy. To carry out such an operation, very high qualifications, experience and professionalism of the surgeon are required; specialists of this level and equipment are concentrated in large oncology centers.
access methods for radical prostatectomy
Radical prostatectomy is used even in the case of very small carcinomas, and removal of part of the prostate gland is indicated only when the surgical intervention is palliative in nature, allowing to restore urination, impaired by massive growth of tumor tissue, stop bleeding or reduce pain.
Gastrointestinal cancer
Tumors of the gastrointestinal tract almost always require radical and even extended operations, since they actively metastasize already in the early stages. Thus, it affects regional lymph nodes even when it penetrates the submucosal layer, while the size of the tumor itself can be quite small. Only in case of carcinoma limited to the mucous membrane, endoscopic resection with preservation of lymph nodes is allowed; in other cases, part (resection) or the entire stomach is removed with lymph node dissection, and the number of lymph nodes is not less than 27. In severe stages, palliative operations are used to restore the patency of the stomach, reducing pain, etc.
The operation is determined by the location of the tumor. If the transverse colon is affected, then a section of the intestine can be resectioned, and if the tumor grows in the left or right half of the large intestine, the hepatic or splenic angles, surgeons resort to removing half of it (hemicolectomy).
Often interventions of this kind are carried out in several stages, where the intermediate stage is the application of a colostomy - a temporary opening on the anterior abdominal wall for the removal of feces. This period is very difficult for the patient psychologically; it requires caring for the colostomy and following a diet. Subsequently, reconstructive operations can be performed aimed at restoring the natural passage of contents to the anus.
Treatment of rectal cancer remains a very difficult task, often requiring the removal of the entire organ, and subsequent plastic surgery cannot be avoided.
Gynecological tumors
Tumors of the uterus almost always require surgical treatment, however, approaches may vary depending on the stage of the cancer and the woman's age. quite often diagnosed in young patients, so the issue of preserving reproductive and hormonal function is quite acute. Most often, for malignant neoplasms of this localization, they resort to complete removal of the uterus, ovaries, lymph nodes and pelvic tissue. With such a volume of intervention, the possibility of having children can be forgotten, and the symptoms of premature menopause are quite severe and difficult to correct. In this regard, young women in the early stages of the tumor are trying to preserve the ovaries, and in case of non-invasive or microinvasive cancer, removal of a fragment of the cervix (conization) is allowed, but in this case one must remember the possibility of relapse.
Many foreign clinics practice organ-preserving operations– radical trachelectomy, when only the neck and surrounding tissues are removed. Such interventions are complex and require a very highly qualified surgeon and special skills, but the result is the preservation of reproductive function.
(mucous membrane) often leave no choice and involve complete removal of the uterus, appendages, lymph nodes, and pelvic tissue. Only in cases of initial forms of the disease, when the tumor does not extend beyond the mucous membrane, are gentle techniques possible to preserve the organ.
Paired organ cancer
Surgical treatment of malignant tumors of paired organs (kidney, lung cancer) provides great opportunities for the use of radical techniques, but on the other hand, if the second organ is also not healthy, then certain difficulties arise.
Removing a kidney in the early stages of the disease gives 90% positive results. If the tumor is small, then you can resort to removing part of the organ (resection), which is especially important for patients with one kidney or other diseases of the urinary system.
kidney resection for cancer
The prognosis after removal of a kidney can be called favorable, provided that the normal function of the other kidney is maintained, which will have to take over the entire process of urine formation.
Removal of the entire lung for cancer is performed in severe cases. Surgeries on the respiratory system are complex and traumatic, and the consequences of removing a lung for cancer can be disability and impairment. However, it is worth noting that the deterioration of the condition depends not so much on the very fact of removal of an entire organ, because the second lung can take over its function, but on the patient’s age, the presence of concomitant pathology and the stage of cancer. It is no secret that mostly older people get sick, so the presence of coronary heart disease, hypertension, and chronic inflammatory processes in the bronchi will make themselves felt in the postoperative period. In addition, chemotherapy and radiation carried out simultaneously also weaken the body and can cause poor health.
surgery options for lung cancer
Surgical treatment of malignant tumors remains the main method of combating the disease, and although most patients do not experience such fear as in the case of the need for chemotherapy or radiation, it is still better to get to the operating table as early as possible, then the result of the operation will be much better, and the consequences will be less dangerous and unpleasant.
The author selectively answers adequate questions from readers within his competence and only within the OnkoLib.ru resource. Face-to-face consultations and assistance in organizing treatment are not provided at this time.
The main role in the treatment of OC belongs to 3 treatment methods: surgical, drug and radiation. Surgical intervention is currently given paramount importance as an independent method and as the most important stage in a complex of treatment measures. For almost all ovarian tumors, a midline laparotomy should be performed. Only this incision allows for a thorough examination of the abdominal organs and retroperitoneal space, facilitates morphological verification of the diagnosis, determines the degree of differentiation and ploidy of the tumor and, most importantly, allows the removal of tumor tissue, in whole or in part. For malignant ovarian tumors, the operation of choice is hysterectomy with appendages and removal of the greater omentum. Some clinics call for additional appendectomy, splenectomy, resection of the affected parts of the intestine, as well as retroperitoneal lymphadenectomy. Theoretically, total retroperitoneal lymphadenectomy should lead to better treatment results, however, those few authors who have sufficient experience in performing such operations note almost the same survival rate of patients who underwent standard surgery and patients with additional lymphadenectomy.
Regarding the issue of treatment tactics for the so-called early stages of the disease, it is necessary to emphasize that even the initial forms of the disease are a big problem for oncologists. At the present time, and probably in the foreseeable future, treatment should begin only with surgery, because only after laparotomy can maximum information about the state of the tumor process be obtained. In this case, surgeons should strive for the maximum volume, taking into account the frequency of relapses and metastases. Of course, taking a realistic approach to the issue of treatment tactics in the early stages of the disease, we have to admit that not all patients undergo radical surgery. In a number of cases, at obvious risk, surgeons are forced to meet the wishes of young women who, for one reason or another, do not agree to radical surgical treatment. In such cases, a strictly individual approach is required. Organ-preserving operations are possible, but only with the most thorough morphological examination of the contralateral ovary, appendages, peritoneum, greater omentum with determination of the degree of differentiation, proliferative potential and other biological parameters of the tumor. With borderline ovarian tumors, stage I of the disease occurs in 90% of cases. During laparotomy, resection or unilateral oophorectomy (adnexectomy) is performed, necessarily a biopsy of the contralateral ovary and removal of the greater omentum. At stages II–III of the process, the uterus and appendages are extirpated and the greater omentum is removed. For confirmed borderline ovarian tumors, postoperative chemotherapy, in our opinion, is ineffective. For well-differentiated tumors of stages IA, B, extirpation of the uterus and appendages, removal of the greater omentum, peritoneal biopsy (at least 10 samples), especially from the pelvic area and subdiaphragmatic surface, abdominal washings, and para-aortic selective lymphadenectomy are usually performed. If stage IA of serous, well-differentiated cancer is confirmed, women who wish to preserve reproductive function can undergo unilateral adnexectomy, biopsy of the contralateral ovary, resection of the greater omentum, and revision of the retroperitoneal lymph nodes. The sparing volume of the operation places great responsibility on the surgeon, since the number of diagnostic errors at all stages of monitoring the patient is quite large. In this regard, the patient must always be under strict supervision (UT, CA 125). Additional treatment - adjuvant chemotherapy - is not usually carried out in most clinics around the world, although, according to our data, postoperative drug treatment, even in monotherapy, increased 5-year survival by 7%. For other histological forms of stage IA and B ovarian cancer, radical surgery is preferable. According to summary data, 5-year survival rate for well-differentiated stage I mesonephroid cancer is 69%, for serous - 85%, for mucinous - 83%, for endometrioid - 78%, and for the undifferentiated form - 55%. Therefore, for this group of patients, after radical surgery, adjuvant monochemotherapy with melphalan, cisplatin, or combinations of SAR, SR is recommended - at least 6 courses, although some authors suggest 3 courses.
All patients with moderately and poorly differentiated tumors IA-B-C, as well as with stages IIA-B-C, are indicated for surgery - extirpation of the uterus with appendages, removal of the greater omentum, followed by polychemotherapy SR/SAR - at least 6 courses (Stenina M.B. 2000 ., Tyulyandin S.A., 2000, YoungR., PecorelliS., 1998). Much more problems arise for clinicians when treating patients with advanced stages of the disease. At present, no one doubts the need to use combined or complex therapeutic measures in the primary treatment of these patients. At the same time, individual aspects and details of combined treatment are contradictory due to the large number of opinions of various researchers regarding tactics, chemotherapy regimens, stages, and duration of treatment. Studying the importance of the sequence of therapeutic interventions in stages III-IV of OC, it has long been concluded that the “surgery + chemotherapy” option significantly improves the survival of patients when compared with those when drug treatment was carried out at the first stage.
This statement can also be justified theoretically: the ineffectiveness of pharmacological drugs is eliminated by removing the bulk of the tumor with weak blood flow; the effectiveness of chemotherapy is associated with the high mitotic activity of small tumors; the smallest residual tumors require fewer courses of chemotherapy, while larger tumors increase the likelihood of the emergence of resistant forms; removal of the main tumor masses leads to relative normalization of the patient’s immune system; If possible, phenotypically resistant tumor cells are removed. Below we will try to briefly decipher the listed criteria for the possible effectiveness of cytoreductive operations. Solid tumors are characterized by relatively poor blood flow, which does not allow achieving effective concentrations of the pharmaceutical drug in tumor tissues and, accordingly, reduces the concentration of the pharmacological drug in tumor tissues and the effectiveness of the treatment. This is especially evident in the central areas of the tumor, where extensive necrosis associated with impaired tissue trophism is common. Adjacent to the necrotic areas are numerous, especially viable areas of malignant tissue supplied by small vessels. This idea is confirmed, albeit indirectly, by the low content of free glucose and high level of lactic acid in the interstitial fluid of solid tumors. All this leads to a temporary decrease in the mitotic activity of malignant cells and, as a result, to a decrease in the effectiveness of chemotherapy, which is tropic to the DNA of the cell only in a certain phase of the cell cycle. For the maximum effect of most pharmacological agents, a fraction of cells with rapid growth is required, therefore, after removing the bulk of cells that are insensitive to chemotherapy, more sensitive small foci (disseminates) with high mitotic activity remain. In addition, removal of a large tumor mass leads to a relative restoration of the immunocompetence of the tumor-carrying organism, primarily due to a decrease in immunosuppression induced by the neoplasm.
The goal of surgical treatment is to remove as much of the primary tumor and its metastases as possible. If complete removal of the tumor is not possible, most of it is removed. It has been shown that patient survival significantly correlates with the size of metastases remaining after surgery. Thus, with the size of the residual tumor not exceeding 5 mm, the average life expectancy corresponds to 40 months; for sizes up to 1.5 cm - 18 months, and in the group of patients with metastases larger than 1.5 cm - 6 months. In this regard, the following standard provisions are currently recommended for the selection of surgical interventions.
Primary cytoreductive surgery involves removing as much of the tumor and metastases as possible before starting drug therapy. Primary cytoreductive surgery is the standard of care for advanced ovarian cancer, especially at stage III of the disease. The goal of cytoreductive surgery should be complete or maximum tumor removal. The role of cytoreductive surgery in FIGO stage IV is controversial, but patients with only pleural effusion, metastases to supraclavicular lymph nodes, or single skin metastases can be treated as for stage III disease.
This volume of surgery is not indicated for patients with metastases to the liver and lungs.
On the other hand, neoadjuvant chemotherapy is an acceptable alternative to cytoreductive surgery for stage IV disease or in patients whose disease cannot be optimally reduced due to technical difficulties.
Intermediate cytoreductive surgery is performed after short induction chemotherapy (usually 2–3 courses). Performing surgery at this stage is an acceptable approach in the treatment of patients in whom the first operation was either trial or unsuccessful.
The “second-look” operation is a diagnostic laparotomy that is performed to evaluate residual tumor in patients without clinical manifestations of the disease after chemotherapy. This tactic is not currently widely used because it does not result in improved survival.
Secondary cytoreductive surgery. Most secondary cytoreductive surgeries are performed for localized relapses that occur after combined treatment. Preliminary analysis showed that candidates for such operations can be identified taking into account prognosis factors. Most often, these are tumors that recur a year or more after completion of primary treatment and responded adequately to previous chemotherapy.
Palliative operations are mainly performed to alleviate the patient’s condition, for example, with intestinal obstruction due to adhesions or with progression of the disease.
In conclusion, it should be noted that to date, methods of surgical treatment for ovarian cancer have remained virtually unchanged, with a few exceptions, while drug treatment has become more effective and continues to improve. New promising methods of therapy at the intersection of genetics, immunology, chemotherapy and radiation therapy are being widely studied. It should be recognized that, probably in the near future, malignant ovarian tumors will be mainly the prerogative of conservative medicine.
Chemotherapy. Systemic chemotherapy is the standard treatment for patients with advanced ovarian cancer. Due to the fact that cytoreductive surgery is not radical, chemotherapy should be started as soon as possible after surgery - usually on days 10-12.
1st line chemotherapy for ovarian cancer
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Combination |
Medicine, dose and treatment regimen |
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Carboplatin(AUC 5-7.5) IV once every 3 weeks, 6–8 cycles |
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Cisplatin - 100 mg/m2 IV once every 3 weeks, 6–8 cycles |
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Cisplatin- 75 mg/m2 IV |
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Carboplatin(AUC 5) i.v. |
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Cisplatin - 75 mg/m2 IV |
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Carboplatin(AUC 5) i.v. |
In most countries of the world, several regimens are considered the standard 1st line chemotherapy:
TR – paclitaxel, 175 mg/m2, IV, as a 3-hour infusion (with premedication), cisplatin –75 – 100 mg/m2, IV drip (with hydration), every 3 weeks.
TC – paclitaxel, 135–175 mg/m2, IV, as a 3-hour infusion (with premedication). carboplatin AUC = 5 – 6 IV, drip, every 3 weeks.
SR - -cisplatin - 75 mg/m2 on the 1st day intravenously (with hydration), and cyclophosphamide - 750 mg/m2 on the 1st day, every 3 weeks.
CC – carboplatin, AUC = 5 – 6 IV drips, cyclophosphamide –750 mg/m2, every 3-4 weeks.
DC – docetaxel, 75 mg/m2, IV drip (with pre- and post-medication), carboplatin AUC = 6 IV, drip or cisplatin 75 mg/m2 IV drip (with hydration) every 3 weeks.
The chemotherapy used allows us to achieve an average time to progression of at least 12 months, and an average life expectancy of up to 24 months (Stenina M.B., 2000, Tyulyandin S.A., 2000). It should be noted that identical results were obtained when carboplatin was used alone.
Let's take a closer look at the main chemotherapy drugs. Cisplatin is one of the most active drugs for the treatment of patients with ovarian tumors. An objective antitumor effect was observed in 32% of patients who had previously received chemotherapy with chlorethylamine or doxorubicin. When using cisplatinau in patients who had not previously received chemotherapy, an objective effect was observed in 60–70% of cases, of which 15–20% were complete, and the 5-year survival rate was 6%.
Carboplatin is a second-generation drug from the platinum-containing group. Unlike its predecessor cisplatin, carboplatin has less nephro- and neurotoxicity and the ability to cause nausea and vomiting. The main side effect of carboplatin is inhibition of hematopoiesis, which can be overcome by the active administration of colony-stimulating factors. The incidence of objective effects when using carboplatin in previously treated patients varies from 9 to 32% and averages 24%. Both platinum drugs have approximately equal effectiveness in the treatment of ovarian cancer if the doses of the two cytostatics are taken in a 4:1 ratio (i.e., carboplatin at a dose of 400 mg/m2 is equivalent in antitumor efficacy to cisplatin at a dose of 100 mg/m2). Several randomized studies have been conducted that compared the effectiveness of combinations containing these two platinum derivatives. In all studies where carboplatin was used at a dose of 300 mg/m2 and higher in combination with other cytostatics (cyclophosphamide, doxorubicin), approximately equal effectiveness was shown in comparison with cisplatin-based combinations. At the same time, regimens containing carboplatin are tolerated much easier by patients. The data obtained show that the combination of carboplatin + cyclophosphamide is the regimen of choice in patients with advanced ovarian cancer.
Paclitaxel is a herbal drug obtained from the bark of certain yew trees. During the second phase of clinical trials, the effectiveness of paclitaxel in second or third line chemotherapy in patients with ovarian cancer treated with platinum was studied. A large number of patients have shown that paclitaxel as monochemotherapy is an effective drug in the treatment of this prognostically unfavorable group of patients. The frequency of objective effects lasting from 3 to 6 months is 20 - 36%. It seems that with increasing doses of paclitaxel, one can expect a higher effectiveness of treatment. The use of paclitaxel for intraperitoneal administration is promising. The high molecular weight and size of the paclitaxel molecule determine the slow absorption of the drug into the blood when administered intraperitoneally. A high concentration of the drug is created in the abdominal cavity (more than 100 times higher than in plasma with intravenous administration), which persists for 5–7 days. A single dose for intraperitoneal administration of paclitaxel is 60 mg/m2 and is recommended for weekly administration for 3–4 weeks. Intraperitoneal administration of paclitaxel can be used for induction chemotherapy in patients with optimally performed cytoreductive surgery, when the size of tumor formations does not exceed 0.5 cm, as well as as 2nd line chemotherapy in patients with minimal manifestations of the disease after induction chemotherapy.
Ovarian tumors are sensitive to chemotherapy. An extremely important factor in successful treatment is the intensity of chemotherapy. This means that when treating patients with disseminated ovarian tumors, it is necessary to use combinations of antitumor drugs, administer cytostatics in full recommended doses, strictly observe the intervals between courses (usually 3–4 weeks from the start of the last course), the number of which should not be less than 6 at a stage induction. The use of monochemotherapy, the use of cytostatics in lower doses, lengthening the interval between courses and reducing the number of chemotherapy courses at the induction stage negatively affect the immediate and long-term results of treatment of patients. When planning treatment, every oncologist must realistically realize that the choice of chemotherapy and the correctness of its implementation is one of the most important factors affecting the quality of treatment and prognosis of life. A few words about how many courses of chemotherapy need to be carried out at the induction stage. The greatest antitumor effect is observed after 3–4 courses of treatment. When carrying out induction therapy, 6–8 courses of drug treatment are considered optimal. Carrying out 10 or more courses does not improve the results of treatment of patients with ovarian tumors. Upon completion of induction chemotherapy, all patients are required to undergo an examination, including a general examination, rectovaginal examination of the pelvic organs, ultrasound and CT scan of the abdominal cavity and pelvis, chest x-ray, and determination of CA 125 in the blood. In 60–70% of patients who underwent optimal cytoreductive surgery at the first stage, followed by 6–8 courses of induction chemotherapy including platinum derivatives, there are usually no manifestations of the disease after treatment. As a rule, CT scan of the abdominal cavity and pelvis and determination of the CA 125 level do not completely exclude the presence of subclinical manifestations of the disease. It has been shown that when the CA 125 level increases to more than 35 U/ml, the presence of a tumor in the abdominal cavity is detected in 100% of patients during repeat laparotomy. Unfortunately, even with complete normalization of CA 125 levels after chemotherapy, 44% of patients have manifestations of the disease confirmed by repeat laparotomy. Thus, the “second-look” operation is the only objective method for assessing the state of the disease and the therapeutic effect. A less invasive method - laparoscopy - cannot fully replace laparotomy, since it has limited capabilities for revision of the abdominal cavity and in approximately 35% of cases the laparoscopic picture of complete regression of the tumor is not confirmed later during laparotomy. Currently, there are no generally accepted approaches to the treatment of residual manifestations of ovarian cancer after induction chemotherapy. If induction chemotherapy included cisplatin at recommended doses every 3–4 weeks. at least 6 courses of treatment, then we can think that the remaining tumor formations represent a clone of cells that have become resistant to the cytostatics used. Treatment tactics in this case are largely determined by the size of the remaining tumor formations. With a maximum size of 0.5 cm, an attempt at intraperitoneal chemotherapy with platinum derivatives or paclitaxel is advisable. It should be noted that the true value of intraperitoneal chemotherapy for improving long-term results of treatment of patients with ovarian cancer has not yet been established. If the size of residual (after chemotherapy) tumor formations in the abdominal cavity exceeds 0.5 cm, it is advisable to stop treatment.
In some patients, removal of the recurrent tumor may be undertaken. Indications for performing such an operation are the presence of a solitary tumor node, the young age of the patient, and the duration of the relapse-free period after the end of induction chemotherapy for more than 12 months. Such a careful selection of patients for repeated cytoreductive surgery is explained by the fact that in the vast majority of patients with recurrent ovarian cancer, repeated surgical treatment does not improve the prognosis of the disease. Despite the progress achieved in the treatment of advanced stage OC, the vast majority of patients experience progression of the tumor process and require 2nd line chemotherapy. The arsenal of antitumor drugs used for 2nd line chemotherapy is unusually large. This is evidence that none of them allows achieving long-term remissions in the majority of patients. The effect of 2nd line chemotherapy can be predicted by knowing the duration of remission. The longer it is, the greater the chance of obtaining a clinical effect when treatment is resumed. Therefore, patients for whom this interval was 6 months. and more, it is advisable to treat relapse with a combination of drugs including platinum derivatives. The frequency of objective effects in this case ranges from 25 to 50%. Typically, 4–6 courses of chemotherapy are carried out with combinations of cisplatin + cyclophosphamidyl or carboplatin + cyclophosphamide. In all other cases, it is recommended to use drugs not included in the induction chemotherapy regimen as 2nd-line chemotherapy. Prescribing paclitaxel at a dose of 135–200 mg/m2 intravenously over 3 hours every 3 weeks for 4–6 courses allows achieving an objective effect in 25–35% of patients with progression of ovarian cancer.
The average duration of effects is 5-8 months. Ifosfamide as 2nd-line chemotherapy is effective in 12-20% of patients with ovarian cancer and can be prescribed at a dose of 2 g/m2 IV for 3 days in combination with mesna. The oral form of altretamine provides an objective antitumor effect in 12–14% of patients. The drug has minimal toxicity. Tamoxifen. In 18% of patients, an objective effect was observed when taking 20 mg of the drug daily. The effect was usually observed in patients with the presence of estrogen receptors in the tumor. The combination of fluorouracil + calcium folinate has moderate effectiveness (10%) in the case of cisplatin-resistant tumors.
Etoposide. Oral administration at a dose of 100 mg for 10-14 days daily is effective in 6-26% of patients. The slight toxicity of the drug allows it to be used for outpatient treatment of weakened patients.
The most effective schemes of the 2nd line chemotherapy for OC are given below.
The immediate and long-term results of treatment of patients with ovarian cancer have improved significantly since the introduction of platinum drugs and combinations based on them into clinical practice. Analysis of long-term treatment results should be carried out taking into account a number of important prognostic factors influencing the final results. Over the past decades, the combination of two main treatment methods, surgical and medicinal, has remained classic. A critical analysis of publications by domestic and foreign authors, who have summarized the experience of leading clinics, indicates that these methods of OC therapy have almost reached their limit in improving long-term treatment results.
Radiation therapy. Drug resistance of the tumor and the high frequency of relapses again forces attention to the use of radiation therapy, which currently occupies a very modest place, despite the noticeable sensitivity of most malignant ovarian tumors to this type of therapy (Mikhina Z.P., 2001). To date, there are 4 options for the use of radiation therapy for OC:
1) Intraperitoneal use of radiopharmaceuticals (RP) - colloidal 32 P or colloidal gold - in the treatment of stages I, II, III of OC without visually detectable metastases, as well as in the treatment of disseminates in the abdominal cavity not exceeding 3 mm. The method is quite effective (85.7%), but often leads to a pronounced adhesive process in the abdominal cavity and low sensitivity to chemotherapy in case of recurrence of the disease. 2) Irradiation of the abdominal cavity and retroperitoneal space using the intermittent strip method. 3) Wide-field technique with possible modifications. 4) Technique of open fields with reinforcement in the pelvic area. When analyzing survival depending on the type of primary treatment, the effectiveness of each method separately is of greatest importance.
Radiation therapy administered to patients with partial regressions after surgery and chemotherapy can achieve full effect in an additional 27% of patients (Mikhina Z.P., 2001). Unfortunately, it should be recognized that at present radiation therapy is unjustifiably used only as a palliative method, mainly for relapses of the disease.
Sex cord stromal tumors are conventionally divided into two types: ovarian (granulosa-stromal cell tumors) and testicular (Sertoli-Leydig cell tumors). This category of neoplasms, which constitute approximately 8% of all primary ovarian tumors, includes granulosa cells, theca cells, Sertoli and Leydig cells, and fibroblasts of stromal origin. All these variants of cellular structures are found both in pure form and in various combinations and proportions. Peak incidence is 50 years (Kerzhkovskaya N.S.).
Granulosa cell tumors of the ovaries are the most common among hormone-producing ovarian neoplasms and account for 1 to 4% of cases. According to the modified classification, in the group of granulosa cell tumors, based on some clinical and morphological features, 2 types of tumors have been identified - adult and juvenile. Tumors of the adult type are much more common - up to 95% compared to the juvenile form. Mostly women aged 50-55 are affected. These are usually unilateral tumors ranging in size from microscopic to occupying almost the entire abdominal cavity. In 10–15%, damage to the capsule is observed. Disseminate in the abdominal cavity, distant metastases are quite rare. Unlike other malignant forms of ovarian tumors, relapses develop late. Cases of relapse of the disease have been described 5, 10 and even 25 years after initial treatment. The histogenesis of ovarian granulosa cell tumor is not well understood, but it has been shown that granulosa in atretic follicles can proliferate. Most granulosa cell tumors produce estrogens, which causes a clear clinical picture, due to which most tumors are detected in stage I. Women of reproductive age experience menstrual irregularities: hyperpolymenorrhea, amenorrhea, amenorrhea followed by acyclic spotting or bleeding. Often during reproductive age, when amenorrhea occurs, doctors at antenatal clinics diagnose “pregnancy” or “early menopause,” and in premenopause, these symptoms are interpreted as manifestations of “menopausal ovarian dysfunction.” In postmenopause, acyclic bleeding of varying intensity is observed, naturally causing the clinician to suspect endometrial cancer. The clinical picture of hyperestrogenism also manifests itself as symptoms of “rejuvenation” (affects the appearance of patients). There is good skin turgor, increased libido, engorgement of the mammary glands, absence of involutive changes in the mammary glands and genitals (juicy pink mucous membranes, well-defined folding of the vagina, the presence of type III-IV reaction of the vaginal smear according to Greist-Salmon, sometimes the “pupil” symptom, the uterus is somewhat more than age norm). Some authors note: the older the patient’s age, the more pronounced the clinical picture of “rejuvenation”
anonymously
Good evening, my mother has stage 3 ovarian cancer, as a result of which ascites developed. We went to cancer hospital No. 62 (Krasnogorsk district). They did a laparoscopy, removed 8 liters (!) of fluid, said that there were metastases on the omentum and abdominal cavity, prescribed 3 chemotherapy (paclitaxel + carboplatin) before the operation and 3 more after. We don't know what to do. Help me please!! Should I start doing chemistry here or go to Israel for treatment (friends advise me to go there)? We are afraid that the chemistry will be done incorrectly, that the equipment in the hospital is not the latest (which could prevent us from making an accurate diagnosis). How can we help our mother... Help, I beg you!...
Good day. The regimen that the doctors prescribed is called the “gold standard” of chemotherapy for treatment, especially the way they divided the regimen (3 - surgery - 3). In this situation, a lot depends on the cellular structure of the cancer, the general condition of the patient, concomitant pathology, age, etc. The chance of a radical cure is very low at this stage, but it exists. If you have the opportunity and your mother’s condition allows you to contact an Israeli clinic as soon as possible, then, of course, try it. But nowhere will you be given a 100 percent guarantee of a cure. And if they start, for example, from November 14, 2011, and in Israel they will start from the beginning of December, then there is no need to hesitate, we must start here, since every day counts. If you have any questions, write, I will try to help you. Sincerely, Lisaev D.A.
anonymously
Thank you very much for the answer. Today my mother had her first chemotherapy. Sorry, but you can find out one more thing... Between chemotherapy courses you need to take a break of 3 weeks. Will it be possible to go to an Israeli clinic during this time and be examined again? And, perhaps, carry out the operation itself there. I just want everything to be checked as accurately as possible. And they said whether the correct treatment was prescribed to us here. We started chemotherapy in Moscow because we didn’t want to waste time. Tell me what you think would be the most correct, please..
| “After numerous clinical studies, leading experts recognized that the “gold standard” in the treatment of ovarian cancer is the Taxol 175 mg/mg regimen as a 3-hour infusion and CarboplatinAiS 5-7.5 every 3 weeks.” Prof. Borisov VM. "Pycc Medical Journal", volume 9, No. 22, 2001 |
“Taxol in combination with cisplatin or carboplatin is one of the most effective induction chemotherapy regimens for patients with disseminated ovarian cancer” |
| “Currently, Taxol is a necessary component of combination chemotherapy for ovarian cancer, preferably included in the first-line treatment regimen, and in patients who have received other chemotherapy, used as a second line” Prof. Perevodchikova NL. “Taxol in clinical practice”, edited by Perevodchikova, p. 8, 2001 |
“There is compelling evidence from phase 3, two large randomized clinical trials that Taxol is the new standard of care cisplatin regimen for the treatment of patients with advanced ovarian cancer.” |
| “Intravenous administration of Carboplatin and Taxol is recommended as a postoperative chemotherapy regimen for newly diagnosed patients with stages II-IV epithelial ovarian cancer” Covens A: Gynecologic Oncology 85.71-80 (2002) |
Ovarian cancer: the GOG 111 randomized trial
Stage III-IV ovarian cancer suboptimal resection [< 1 см ]M.J. Piccart et al, Journal of the National Cancer Institute, Vol. 92, No. 9, May 3,2000
CONCLUSION:
the Taxol + Cisplatin combination is statistically significantly superior to the Cyclophosphamide + Cisplatin combination in terms of:
6-year survival rate
(M.J. Piccart et al., Proceedings ESMO 2002, Abstract 395, p. 109)Combination of Taxol and Carboplatin
Given the nephrotoxicity, ototoxicity and neurotoxicity of cisplatin, subsequent studies were conducted to study the effectiveness of the combination of Taxol and Carboplatin. As a result of these studies, equal therapeutic efficacy, but significantly less toxicity of this combination was demonstrated. (Prof. Borisov V.I. “Russian Medical Journal”, volume, No. 22, 2001)
Results of randomized trials in advanced ovarian cancer
Taxol + Cisplatin versus Taxol + Carboplatin combination
(Gorbunova V.A. “Taxol 6 in clinical practice”, edited by Perevodchikova, p. 172., 2001)
