Cytoreductive Surgery

Peritoneal metastases (PM) from various tumors can now be effectively treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). However, this is a complicated treatment that is challenging to apply, and for excellent outcomes, careful patient selection is required. The purpose of cytoreductive surgery is to completely eradicate all macroscopic cancer. This is accomplished through peritonectomy procedures and, if necessary, en-bloc resection of the viscera. Using them depends on how severe the PM is. Only the damaged peritoneum is removed; the normal peritoneum is not removed.

Cytoreductive Surgery Types

The type of cytoreductive surgery has not been cross-organ defined, however, the resection pattern can be easily divided into three forms depending on whether metastatic or disseminated lesions are present and whether the underlying tumor is resectable. Primary tumor resection (PTR) with or without resection of metastasis/dissemination as much as feasible is Type 1 of cytoreductive surgery, which is common and important. This method involves total resection of the original tumor. The amount of metastatic and disseminated lesions that are removed depends on the number and extent of metastasis/dissemination because metastasis/dissemination cannot be removed. Cytoreductive resection of the main tumor is type 2, which has no metastasis or disseminated but invades into inoperable anatomical structures. Whether or not related anatomical structures can be removed by extensive surgery depends on both the location of the structure and the health of the patient. In this case, radiotherapy is typically advised; however, if radiotherapy is not suitable due to the large tumor size, an unsuitable tumor site for radiation therapy, or radioresistant histology, cytoreductive surgery may be suggested instead. The persistent tumor in this type 2 is only local. A cure might even be possible with postoperative radiation and a little amount of residual tumor tissue. The third type is a hybrid of types 1 and 2.

Three types of cytoreductive surgery have been identified for the treatment of ovarian cancer, depending on when it is performed: first is primary cytoreductive surgery (PDS), which refers to debulking as the primary treatment; second is interval cytoreductive surgery (IDS), which refers to debulking followed by neoadjuvant chemotherapy; and the third is secondary cytoreductive surgery (SDS), which refers to debulking for recurrent or residual tumors developed.  Regarding the minimal requirement for removed tumor volume, residual tumor volume in ovarian cancer is classified into two categories (optimal and suboptimal surgery) based on the evidence demonstrating a favorable correlation between the maximum size of residual lesions and survival.

Cytoreductive Surgery Benefits

The combination of cytoreductive surgery and HIPEC is a potent, ground-breaking treatment that has many advantages over conventional intravenous chemotherapy, including:

• Survival potential. Patients who receive HIPEC can recover from the operation, resume regular activities, and even survive the condition, according to studies.
• Limited side effects. Compared to conventional chemotherapy, HIPEC has fewer adverse effects because the chemotherapy is not administered into the patient's blood. This means patients don’t have classic chemotherapy side effects, such as hair loss and nausea.
• Higher and more effective doses. Doses that are greater and more effective are possible because the medication does not enter the blood. This combats the disease more effectively.
• Deeper penetration into tumor cells. Heating the solution increases the chemotherapy's ability to kill cancerous cells while having less effect on healthy cells. Chemotherapy can reach the peritoneal surfaces more deeply thanks to the heat. The tumor cells the doctor was unable to observe can be killed here.
• Two procedures in one. Cytoreductive surgery plus HIPEC requires only one visit to the operating room as opposed to several treatments spaced out over weeks or months.

Cytoreductive Surgery Indications

The most crucial aspect of surgical oncology is the so-called R0 resection, which entails the full removal of all malignancies, both macroscopically and microscopically. Cytoreductive surgery, designed as an R2 resection in situations where R0 resection is completely impossible, goes against established rules in surgical oncology. Cytoreductive surgery cannot, in theory, cure the disease because residual cancer cells will always proliferate again. Cytoreductive surgery, however, has been thought to have a possible survival advantage in the following particular circumstances. The goal of the first scenario is to delay tumor progression and even extend survival in patients with unresectable but slow-growing and proliferating malignancies such as pseudomyxoma peritonei (PMP) and thymomas with peritoneal and pleural spread. For individuals in whom a synergistic effect of cytoreductive surgery and systemic therapy, and radiotherapy may be expected (the second scenario, possibly the predominant one) is applicable.  It may be beneficial to debulk a significant portion of resting cells during the cell cycle to improve the efficacy of systemic therapy. Reduced tumor volume may also help to lessen the radiation field and increase the radiotherapy's adverse effects. For patients with metastatic illness, the third scenario involves a bulk tumor mass that may result in side effects that interfere with systemic therapy, such as GI obstruction or bleeding in GI malignancies and malignant skin ulcers or bleeding in breast cancer. In this case, cytoreductive surgery might make systemic therapy more tolerable and have a stronger anti-tumor effect. In all circumstances, cytoreductive surgery may help avert a decline in quality of life, particularly if the primary tumor may manifest potentially fatal symptoms during nonsurgical therapies. Regardless of the little information supported by prospective research, cytoreductive surgery has been empirically recommended for a variety of advanced tumors including ovarian cancer, urological cancers, GI cancers, breast cancer, brain tumors, and several thoracic malignancies.

Why is Cytoreductive Surgery Performed?

Some kinds of ovarian cancer, endometrial or uterine cancer, as well as other malignancies that have migrated to the peritoneum (lining of the abdomen), may be treated with cytoreductive surgery to relieve symptoms brought on by big tumors and to slow their progression.

For several ovarian tumors, it is frequently used in conjunction with chemotherapy as the initial course of treatment. Because most women with ovarian cancer are identified when their disease is more advanced, cytoreductive surgery is a primary treatment option. Advanced ovarian cancer typically responds better to cytoreductive surgery and chemotherapy than other advanced malignancies.

The American Cancer Society reports that by the time ovarian cancer is discovered, roughly 80% of cases are well advanced. This is probably because many patients have symptoms that could be mistaken for other illnesses. Asymptomatic or low-risk women are rarely screened for ovarian cancer because there are no suggested screening techniques for the condition.

The benefit of cytoreductive surgery in advanced patients is that it removes all cancer or leaves very small amounts of cancer from the body, which may make chemotherapy more effective. Chemotherapy is more effective against smaller or cytoreduced tumors. Cytoreductive surgery aims to leave as little cancer as possible, if not any cancer at all.

Preoperative Evaluation

The usual examination used to assess patients before surgery is a contrast-enhanced CT scan of the thorax, abdomen, and pelvis. It can anticipate the severity of the disease and rule out significant distant metastases. Helical CT was found to have a sensitivity of just 30-50% for peritoneal tumors less than 1 cm, as opposed to 90-95% for bigger tumor deposits. Esquivel et al. discovered that the preoperative CT peritoneal cancer index (PCI) score underestimated the degree of carcinomatosis in 35% of patients in multi-institutional research. In recent studies, some authors have claimed that MRI is more reliable for detecting nodules smaller than 1 cm, whereas other writers have shown no difference. Results from MRIs also depend on the interpreter's level of experience. By identifying extra-abdominal (mediastinal or supraclavicular) lymphadenopathy, PET or PET-CT scans may provide additional information in this direction. However, compared to a standard, high-quality CT scan, PET or PET-CT scans do not provide any additional information for the evaluation of the volume and distribution of peritoneal disease. Patients with resectable disease from those with non-resectable malignancy may be identified using a CT scan for mucinous carcinomatosis in combination with two distinct radiologic criteria (segmental obstruction of the small bowel and the presence of tumor nodules larger than 5 cm in diameter on small bowel surfaces or directly nearby small bowel mesentery). However, the CT scan's sensitivity for malignant nodules smaller than 5 mm, particularly on small intestinal surfaces, is still low. Particularly in individuals with postoperative abnormalities, carcinomatosis with implants less than 5 mm would not be detected or would be underestimated in their distribution.

Cytoreductive Surgery Preparation

You must be completely informed about the process, including any potential advantages and hazards, to be prepared for cytoreductive surgery or any other cancer surgery. Think about making a list of inquiries and discussing them with your treatment team. Check if your surgeon has a lot of expertise doing this treatment. For instance, a gynecologic oncologist (a medical professional who specializes in diseases of the female reproductive system) should practice cytoreductive surgery for ovarian cancer. It's crucial to let your medical team know if you want to keep having children after cytoreductive surgery for ovarian cancer as both ovaries might need to be removed during the procedure.

Your care team may provide you with more thorough advice on how to get ready before your operation date. It is advised that you stop smoking for as long as you can if you currently do so. Smoking decreases blood flow, which makes it more difficult for your body to recover. Smokers are more likely to experience surgical problems. All drugs and dietary supplements you use should be mentioned to your care provider. You might need to temporarily cease taking some drugs before surgery. You could be instructed to abstain from food and liquids beginning at midnight the night before surgery.

Cytoreductive Surgery Procedure

Cytoreductive surgery may entail surgically removing the uterus, fallopian tubes, and ovaries, depending on the stage and degree of the patient's cancer. This procedure is known as a bilateral salpingo-oophorectomy (BSO) and complete abdominal hysterectomy. When both ovaries are excised in premenopausal women, surgical menopause will result.

The lymph nodes and omentum, which is the fatty tissue that covers the intestines, liver, and stomach, may also need to be excised. The affected intestinal tissue may need to be removed in some patients with advanced cancer. However, this is only done if the surgeon considers the patient can be made tumor-free with colon resection and there are no additional tumors in the pelvis and abdomen.

Gynecological oncologists should undertake cytoreductive surgery since the patient results (survival rates) are better and the procedure is typically accomplished via an open, abdominal approach. When no cancer is still present following surgery, the patient has been optimally cytoreduced.

Doctors frequently perform a diagnostic laparoscopy to establish the type of tumor present, arrange genetic testing, and recommend your patient for upfront (neoadjuvant) chemotherapy if medical imaging (such as a CT scan) indicates that they have advanced cancer. In these situations, They postpone cytoreductive (or cytoreductive) surgery by 2 or 3 months to give chemotherapy time to reduce the tumor upfront. This has several advantages over upfront surgery for the patient.

To determine the type of cancer, the organs and tissues taken during the cytoreductive procedure will be studied under a microscope. After cytoreductive surgery, almost all patients will require chemotherapy. Less cancer is present after cytoreductive surgery, which makes chemotherapy more effective.

The prognosis for ovarian cancer relies on the volume of tumor that has to be removed during surgery and how well the malignancy responded to chemotherapy. Compared to the general Australian population, women who are diagnosed with all types and stages of cancer have a 45% overall likelihood of living for five years.

Cytoreductive Surgery Recovery

When the malignancy is optimally cytoreduced as compared to sub-optimally cytoreduced, the benefits of the operation are significantly more noticeable. It is crucial to be under the supervision of skilled professionals such as a gynecologic oncologist for ovarian cancer therapy since evidence suggests that surgeons and care teams with extensive experience in this process are more likely to produce optimal results.

It could take a few weeks or months to get back to your routine after surgery. Any discomfort or other symptoms should be discussed with your doctor at this time. In addition to advising on how to manage other symptoms, your medical team may prescribe medications to treat pain.

Cytoreductive Surgery Risks

Premenopausal women who undergo cytoreductive surgery with both ovaries removed will experience an early onset of menopause. Vaginal dryness and hot flashes are two signs of menopause. Women who have both ovaries removed are likewise unable to become pregnant. Before surgery, patients should discuss these concerns with their surgeon. Cytoreduction carries dangers much like any other type of surgery. The following are examples of possible risks and adverse effects when treating advanced ovarian cancer:

• Pain
• Bleeding
• Bladder difficulties (frequent urination, urinary tract infection (UTI), uncontrollable urination)
• Lymphedema (swelling)
• Reduction in fertility
• Infertility issues
• Menopause
• Blood clots
• Infection
• intestinal obstruction

It's crucial to get in touch with your care team frequently as you heal. Following a cytoreductive procedure, if you experience any of the following symptoms, contact your care team right away or get other medical help:

• Difficulty with urination
• Excessive vaginal bleeding
• Fever or infection signs
• Increasing abdomen discomfort
• Leg discomfort, swelling, or redness
• Chest pain, difficulty breathing, or a bloody cough

Conclusion

Cytoreductive surgery has been clinically supported in a variety of malignant tumor types even though it is an intended incomplete resection against the concept of surgical oncology. Although recent trials have tended to demonstrate a negative impact of cytoreductive for renal cell cancer (RCC), colorectal cancer (CRC), and breast cancer, this is primarily due to the survival improvement of nonsurgical systemic therapy alone. Positive statistics from randomized controlled trials (RCTs) have been shown in ovarian cancer, RCC, CRC with peritoneal distribution, and breast cancer. Cytoreductive surgery continues to be an effective treatment for slowly developing, borderline malignant tumors such as pseudomyxoma peritonei (PMP) and thymomas. Additionally, the synergistic effects of cytoreductive surgery and innovative systemic medication in a cross-organ approach may result in prolonged survival for chosen patients, according to a recent understanding of tumor heterogeneity and clonal evolution responsible for cancer and drug resistance. Future research is needed to determine the best candidates for cytoreductive surgery, the best time to perform it, and how each tumor will benefit prospectively from it in terms of survival.