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Cancer of the ovary, fallopian tube, and peritoneum: Surgical cytoreduction

Cancer of the ovary, fallopian tube, and peritoneum: Surgical cytoreduction
Literature review current through: Sep 2023.
This topic last updated: Jan 24, 2023.

INTRODUCTION — Epithelial, germ cell, and stromal cancers of the ovary, fallopian tube, and peritoneum are staged surgically. In this topic, we will focus on epithelial carcinomas and generally refer to carcinoma at these sites as epithelial ovarian carcinoma (EOC), but distinctions between sites, where present, will be addressed.

Cytoreductive surgery and chemotherapy are the cornerstones of therapy for most stage II, III, or IV EOC. There are several potential benefits of aggressive primary surgical management, particularly for patients with advanced disease:

Optimal response to postoperative systemic chemotherapy is achieved in the setting of minimal disease burden.

Disease-related symptoms (eg, abdominal pain, increased abdominal girth, dyspnea, early satiety) are related to tumor burden; removal of bulky disease rapidly improves symptoms and quality of life.

Ovarian neoplasms produce multiple cytokines, at least some of which are immunosuppressive (eg, interleukin 10, vascular endothelial growth factor) [1-3]. Removal of tumor bulk may improve or restore host immune competence.

Primary surgery ensures accurate diagnosis and ensures tumor tissue for additional testing.

This topic will discuss issues related to cytoreduction of EOC. Clinical features and diagnosis, surgical staging, and chemotherapy are reviewed separately:

(See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis".)

(See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging".)

(See "Patient selection and approach to neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer".)

(See "Adjuvant therapy of early-stage (stage I and II) epithelial ovarian, fallopian tube, or peritoneal cancer".)

(See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer".)

TERMINOLOGY — The terminology regarding extent of cytoreduction is as follows:

Primary cytoreduction – Cytoreduction performed before chemotherapy.

Interval cytoreduction – Cytoreduction performed after neoadjuvant chemotherapy.

Secondary cytoreduction – Cytoreduction performed after disease recurrence.

Complete cytoreduction – Cytoreduction to no grossly visible disease.

Optimal cytoreduction – Optimal cytoreduction, as defined by the Gynecologic Oncology Group, is residual disease ≤1 cm in maximum tumor diameter [4-9].

Suboptimal cytoreduction – Suboptimal cytoreduction is defined as residual disease >1 cm in maximum tumor diameter.

GOAL AND EFFICACY — The volume of residual disease remaining after cytoreductive surgery correlates inversely with survival (figure 1) [4-11]. Thus, the goal of surgery is to remove all macroscopic disease (ie, complete cytoreduction) [7,10,12-16]. Optimal cytoreduction is a reasonable option if reduction to no gross disease is not possible. Neoadjuvant chemotherapy should be strongly considered for those patients who are not candidates for optimal cytoreduction. (See "Patient selection and approach to neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer", section on 'Patient selection'.)

The mechanism for the survival benefit with cytoreduction is that chemotherapeutic drugs exert their maximum effects on small tumors that are well-perfused and, therefore, mitotically active. Larger tumor size is associated with poorer perfusion and a greater chance of sublethal cellular damage, as well as the emergence of multidrug-resistant clones [17]. These pharmacologic principles are supported clinically by the observation that both the relapse-free interval and median survival are inversely related to the size of the largest residual tumor mass at the completion of initial debulking prior to the start of induction chemotherapy [10].

The impact of cytoreduction on survival is illustrated by the following studies:

In a 2011 meta-analysis of 11 retrospective studies of primary surgical treatment for advanced EOC, survival was better with optimal (≤1 cm) versus suboptimal (>1 cm) cytoreduction (hazard ratio [HR] 1.36, 95% CI 1.10-1.68) and better with complete (no gross residual disease) versus optimal cytoreduction (HR 2.20, 95% CI 1.90-2.54) [18].

In a 2013 meta-analysis of 18 studies (both retrospective and prospective studies) of patients with stage IIB or higher EOC who underwent cytoreduction and platinum/taxane chemotherapy, each 10 percent increase in the proportion of patients undergoing complete cytoreduction to no gross residual disease was associated with a 2.3-month increase in median survival compared with a 1.8-month increase for optimal cytoreduction (defined as residual disease ≤1 cm) [12].

In a 2002 meta-analysis of 81 ovarian cancer patient cohorts, each 10 percent increase in maximal cytoreduction was associated with a 5.5 percent increase in median survival time [10]. Patients with less than 25 percent maximal cytoreduction of disease had overall survival of 22.7 months, while patients with 75 percent or greater maximal cytoreduction had an overall survival of 34 months.

Whether "ultra-radical" procedures (eg, diaphragm peritonectomy or resection, multiple resections of the bowel, liver resection, partial gastrectomy, cholecystectomy, splenectomy [with or without distal pancreatectomy]) are associated with improved outcomes is unclear. In a review of three retrospective studies including 924 patients with advanced stage EOC, ultra-radical compared with standard cytoreduction was associated with a lower risk of mortality (adjusted HR 0.6, 95% CI 0.4-0.8; two studies, 397 patients), but the certainty of evidence was very low [19]. By contrast, in a third study within this analysis ultra-radical compared with standard cytoreduction was associated with increased disease progression (adjusted HR 1.6, 95% CI 1.1-2.3; one study, 527 patients), but the certainty of evidence was also very low.

PREDICTING FEASIBILITY OF CYTOREDUCTION — Prior to an attempt at debulking, predicting which patients will be able to have at least an optimal cytoreduction can be useful, given the importance of an optimal cytoreductive effort on outcome and the potential morbidity associated with performance of major abdominal surgery.

Our approach — In patients who are surgical candidates, we primarily use computed tomography (CT) and physical examination for decision making regarding feasibility of complete cytoreduction.

We offer cytoreduction if findings on CT imaging and physical examination suggest complete cytoreduction is possible, and we offer neoadjuvant chemotherapy if these studies show disease features not amenable to complete cytoreduction (eg, extra-abdominal or extensive retroperitoneal disease, large tumor bulk, bulk disease in the porta hepatis region, extensive bowel involvement, parenchymal liver involvement, mesenteric root involvement). If findings on imaging do not show obvious disease-related contraindications to primary cytoreduction, then we proceed with diagnostic laparoscopy to assess cytoreductive feasibility [20] or we perform a minilaparotomy to assess the extent of disease, which provides the benefit of tactile assessment (see "Patient selection and approach to neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer"). Some patients who are not candidates for primary cytoreduction may be candidates for interval cytoreduction. (See 'Interval cytoreduction' below.)

Assessment of patient factors including age, performance status, medical comorbidities, and preoperative nutritional status should also be considered, as some patients may not be able to tolerate cytoreductive surgery [21-24].

In a large case series, the likelihood of optimal cytoreduction was significantly higher in patients who were American Society of Anesthesiologists class 1 or 2 (table 1), had no carcinomatosis (defined as tumor nodules diffusely covering the majority of the surfaces of bowel serosa and the parietal peritoneum of the abdomen and pelvis), or were operated on by a surgeon who performed radical procedures in more than 50 percent of patients operated [25]. A high preoperative cancer antigen 125 (CA 125) level has also been found to be modestly predictive of a lower likelihood of optimal cytoreduction [26,27]. In a meta-analysis of preoperative serum CA 125 levels, a level ≥500 units/mL had sensitivity and specificity of 69 and 63 percent, respectively, for predicting optimal cytoreduction [28].

Preoperative imaging — Preoperative imaging (CT, magnetic resonance imaging, or positron emission tomography) lacks the necessary precision to guide clinical management and has not been validated in large studies [21,29-31]. However, in some cases, it can be useful for predicting suboptimal cytoreduction and thus selecting patients for neoadjuvant chemotherapy. Findings on imaging that have prompted use of neoadjuvant chemotherapy include stage IV disease, large-volume ascites (>1000 mL), bulky (>1 to 2 cm) disease in the upper abdomen, omental extension to the spleen, suprarenal adenopathy, parenchymal liver disease, diaphragmatic disease, and peritoneal carcinomatosis [29].

Laparoscopy — As discussed above, if preoperative imaging does not show obvious disease-related contraindications to primary cytoreduction, then diagnostic laparoscopy can be an effective way to assess cytoreductive feasibility [20]. The use of laparoscopic scoring methods may detect features like omental cake, extensive agglutinated intraabdominal metastatic disease, extensive peritoneal and diaphragmatic carcinomatosis, mesenteric retraction, bowel and stomach infiltration, spleen and/or liver superficial metastasis, and, along with imaging findings, may provide benefit in determining the ability to perform an optimal cytoreduction and avoid futile laparotomy [20,32]. In a multicenter randomized trial in which 201 patients with advanced ovarian cancer were assigned to either diagnostic laparoscopy or primary surgery, fewer patients in the laparoscopy group underwent primary cytoreductive surgery (62 versus 94 percent), and fewer patients had a futile laparotomy (defined as >1 cm residual disease; 10 versus 39 percent, relative risk 0.25, 95% CI 0.13-0.47) [20].

If diagnostic laparoscopy is performed, it should be done by a gynecologic oncologist experienced in laparoscopic assessment of cancer.

Fagotti score — The Fagotti score is a quantitative, laparoscopy-based model for predicting the chance of optimal cytoreduction [32]. It includes seven parameters: omental caking, peritoneal carcinomatosis, diaphragmatic carcinomatosis, mesenteric retraction, bowel and/or stomach infiltration, and liver metastasis. Each parameter is scored with a value of two points. In the initial model, a score of ≥8 identified patients undergoing suboptimal (>1 cm residual disease) with sensitivity 30 percent, specificity 100 percent, positive predictive value 100 percent, and negative predictive value 70 percent.

CYTOREDUCTION PROCEDURES

General principles

Surgical cytoreduction should be performed by a gynecologic oncologist experienced in this surgery since achieving optimal cytoreduction depends partly on the judgment, experience, skill, and aggressiveness of the surgeon.

The majority of bulky disease is typically distributed in the pelvis, omentum, and right diaphragm, but bulky upper abdominal disease may also be present. Thus, the surgical team should be prepared to undertake potentially extensive surgery, such as splenectomy, bowel resection, partial hepatectomy, and diaphragmatic resection to achieve an optimal procedure. Such extensive surgery should be utilized only in a setting where optimal cytoreduction is determined feasible.

Extensive upper abdominal debulking procedures may be necessary to achieve optimal primary cytoreduction and are associated with improved survival [33-36]. In a series of 141 patients with advanced EOC who underwent such procedures, there were two deaths, and major complications occurred in 22 percent of patients [37].

Pelvic anatomy is frequently distorted in patients with ovarian carcinoma. Resection of confluent, bulky disease by a retroperitoneal technique minimizes the risk of injury to the bladder or ureters and results in excellent access to blood supply.

The most difficult areas should be assessed and approached first. If resection of the bulk of disease appears technically feasible, as it should in most patients, an aggressive surgical approach aimed at resection of all or most visible disease is warranted. There is no evidence of increased morbidity with complete versus optimal cytoreduction.

Sharp dissection and electrocautery, including aggressive peritoneal stripping of the diaphragm and abdominopelvic surfaces, are the traditional methods used to achieve complete cytoreduction. The cavitational ultrasonic surgical aspirator, carbon dioxide laser, and argon beam coagulator have been used as adjuncts to these conventional techniques [38-43]. Surgeons should select equipment and instruments in accordance with availability and their skills.

Role of pafolacianine — Pafolacianine (Cytalux), a fluorescent drug that binds to folate receptors (which are commonly overexpressed in ovarian cancer tumors), is an optical imaging agent that may be used intraoperatively as an adjunct to visual inspection and palpation to aid in identification of metastatic lesions [44]. While it was approved by the US Food and Drug Administration in November 2021 for this indication [45], it is not widely used given its unclear benefit and potential for increased morbidity.

Injection of pafolacianine occurs as a single infusion (0.025 mg/kg diluted in 250 mL of 5% dextrose) one to nine hours prior to surgery [46]. During surgery, a surgeon with training in use of a near-infrared fluorescence (NIRF) imaging utilizes this technology to identify lesions that may not have been detected with standard white light or palpation.

Pafolacianine has been evaluated in both phase II and phase III trials [47,48]. In the phase III open-label trial including 150 patients with ovarian cancer, most of which were serous adenocarcinoma and advanced stage, NIRF imaging identified additional lesions in 36 of 109 patients (33 percent; sensitivity: 83 percent; false-positive rate: 33 percent) [48]. This rate was highest (39 percent) among patients undergoing interval debulking surgery. Of the 150 patients evaluated for safety, drug-related adverse events occurred in 30 percent of patients and included nausea (18 percent), vomiting (5 percent), and abdominal pain (4.7 percent). Adverse reactions were mostly mild or moderate and often resolved within 24 hours of onset. Pafolacianine may also be associated with increased surgical morbidity. In the phase II trial, false-positive lesions occurred in 29 of 225 (13 percent) lesions sampled; while the majority of these lesions occurred in the lymph nodes, they also occurred in the colon, ileum, and appendix [47].

Splenectomy — If tumor nodules extend into the splenic hilum, splenectomy is reasonable if optimal cytoreduction is then possible [49-51]. The spleen is mobilized, and the splenic vessels are ligated, taking care to avoid injury to the tail of the pancreas. Rarely, it may be necessary to resect the tail if involved by contiguous cancer spread.

A series of 112 ovarian cancer patients who underwent splenectomy as part of primary or secondary cytoreductive surgery reported perioperative morbidity and mortality of 15 and 5 percent, respectively [51]. Median survival was 1.8 years.

Patients who undergo splenectomy should receive prophylactic vaccines. (See "Prevention of infection in patients with impaired splenic function".)

Partial hepatic resection — Very rarely, hepatic disease is present that affects only a segment of a lobe. In these unusual cases, a partial hepatectomy can be performed to achieve optimal cytoreduction [49]. Generally, this can be performed with use of intense cautery, which dissects the liver parenchyma. The parenchyma can be finger fractured along cautery dissection and intact blood vessels ligated as they become accessible. Some surgeons believe the use of an argon beam coagulator is highly effective for obtaining hemostasis after a partial hepatectomy.

Parenchymal hepatic metastases are not necessarily a contraindication to initial cytoreductive surgery [52-54]. In one series of 84 patients with stage IV disease who underwent initial debulking surgery, 37 (44 percent) had parenchymal liver metastases [52]. Median survival was highest in patients in whom optimal debulking of both intrahepatic and extrahepatic disease was achieved (survival 50 versus <20 months in patients with suboptimal debulking). Nevertheless, the risk/benefit ratio for optimal hepatic cytoreduction may be unfavorable if hepatic disease is bulky or involves major vessels.

Diaphragmatic disease — Diaphragmatic disease can be approached by stripping or scraping the peritoneal surface [55]. Alternatively, the liver can be partially retracted; the hepatic ligament divided; and the affected portion of the membranous diaphragm resected using ultrasonic dissection, electrocautery, or argon beam laser. In cases where full-thickness involvement of the diaphragm is present, resection of the diaphragm has been reported [56-59].

The value of cytoreduction of the diaphragm was illustrated in a series of 181 patients with ovarian cancer involving the diaphragm that reported diaphragmatic surgery (stripping of the diaphragmatic peritoneum, full or partial thickness diaphragm resection, excision of nodules, or use of the Cavitron ultrasonic aspirator) was associated with improved five-year overall survival (53 versus 15 percent when diaphragmatic surgery was not performed) [60]. The survival advantage with diaphragmatic surgery was observed even in the subset of patients who were optimally cytoreduced (55 versus 28 percent).

Most complications during debulking of diaphragmatic disease are due to breaching the pleural cavity and increasing pleural effusions. In cases where the pleural cavity is entered, a primary repair or repair with mesh (if a large defect) should be performed. When closing the defect, suction can be applied to the pleural cavity to remove excess air and reduce pneumothorax. Postoperative pneumothorax or large pleural effusions can be managed by chest tube if necessary. Routine placement of a chest tube is not recommended.

Bowel resection — Common sites of bowel resection in debulking include small bowel, ileocecum, transverse colon, and rectosigmoid. It is important to consider that gastrointestinal surgery can add significant morbidity to surgical treatment. A thorough assessment of the intraabdominal findings should be performed prior to attempted resection. Bowel surgery is of little value if there are other areas of grossly unresectable disease, except to relieve gastrointestinal obstruction. Ultraradical surgery, including complex or multiple bowel resections, is associated with substantial morbidity and potential perioperative mortality, particularly in nutritionally depleted patients.

Rectosigmoid colon resection should be attempted in patients with bulky abdominal disease if the procedure provides an opportunity for maximal cytoreduction or the patient has obstructive symptoms [61-65]. Rectosigmoid implants constitute the bulk of intestinal involvement in patients undergoing primary cytoreductive surgery for EOC. Small-volume disease can be simply shaved off, taking advantage of the fact that these implants are often only superficially invasive. Bulkier implants may require bowel resection and reanastomosis [49,62]. It cannot be overemphasized that these procedures are indicated only if optimal cytoreduction is possible or if obstruction is present.

A diverting colostomy or ileostomy should be considered after a rectosigmoid resection or ileocecectomy, especially in patients with poor nutritional status (preoperative albumin <3 g/dL), multiple bowel resections, or with a short distance from the anastomosis to the anal verge [66]. Diverting ileostomy has been associated with reduced morbidity in the case of an anastomotic leak; however, it can also have potential complications, including dehydration, prolapse, necrosis, and need for future reversal surgery.

In an unstable patient, if bowel resection is contraindicated or if optimal cytoreduction is not achievable at other sites, an intestinal bypass procedure can be done instead. In most cases, this can be accomplished with a loop ostomy placement (either colostomy or ileostomy). In circumstances where a loop diversion is not possible, the proximal and distal bowel can simply be approximated without resection of the involved segment, thus bypassing the area of resistance to permit flow of gastrointestinal contents. The procedure is usually well-tolerated and results in palliation, but it may be associated with blind loop syndrome with bacterial overgrowth or potential risk of perforation. An alternative to surgery is placement of a stent. (See "Enteral stents for the management of malignant colorectal obstruction".)

Role of posterior exenteration — Posterior exenteration is rarely performed but may be appropriate for patients with invasion into the sigmoid colon. This procedure involves a retroperitoneal radical hysterectomy with en bloc resection of the adnexa, cul-de-sac tumor, involved peritoneum, and any involved rectosigmoid colon. Since ovarian cancer usually does not extend through the peritoneum, the retroperitoneal approach facilitates resection of the confluent pelvic disease. This procedure usually is not appropriate for patients who have unresectable upper abdominal disease because of the procedure's high morbidity and low potential for cure in such patients. An exception would be in patients with impending bowel obstruction in which resection or diversion would be appropriate. (See "Exenteration for gynecologic cancer".)

Bladder or ureteral resection — Resection of the bladder or ureters is rarely necessary to achieve optimal debulking unless the tumor has invaded the bladder or obstructed the ureter or the ureter is entrapped by pelvic disease [49]. Resection of these structures may require complete mobilization of the bladder by dividing lateral peritoneal attachments to accommodate the decreased length of the remaining ureter. Ureteroneocystostomy with psoas hitch provides an excellent result. Initially, these anastomoses are not watertight, and drainage of the pelvis by closed suction is prudent. Placement of ureteral stents is based upon the surgeon's preference since there is no evidence for or against their use.

Lymphadenectomy — Pelvic and paraaortic lymph node sampling is often a component of surgical staging of ovarian cancer because the presence of positive lymph nodes is one criterion for stage III disease. However, many patients have grossly visible omental or abdominal disease, which also meets criteria for stage III; in these patients, lymph node sampling is not necessary to assign stage. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging", section on 'Lymph node evaluation'.)

We suggest against routinely performing systematic pelvic and paraaortic lymphadenectomy, consistent with the practice of most gynecologic oncologists. In our practice, for patients with apparent stage I or II disease (disease appears to be limited to the ovaries or pelvis), we perform bilateral lymph node sampling to detect micrometastases that would change the stage. For those with known stage III or IV disease, if complete or optimal cytoreduction is being attempted, we resect grossly suspicious nodes with the goal of achieving cytoreduction to either no gross residual disease or to ≤1 cm residual disease if resection to no gross residual disease is impossible. If there is extensive disease and cytoreduction to ≤1 cm is not possible at other metastatic sites, we do not remove enlarged nodes.

Accumulating evidence from randomized trials [67-69], particularly the Lymphadenectomy in Ovarian Neoplasms (LION) trial [67], has shown that routine systematic pelvic and paraaortic lymphadenectomy does not improve overall survival in ovarian cancer patients and results in increased perioperative morbidity. The LION trial included 647 participants with stage IIB to IV EOC who underwent complete resection to no grossly visible disease and had no visible nodal metastases and were then assigned to either undergo or not undergo pelvic and paraaortic lymphadenectomy [67]. In the lymphadenectomy group, positive nodes were detected in 55.7 percent. More than 80 percent of patients in both groups were treated with platinum-based chemotherapy. Compared with no lymphadenectomy, lymphadenectomy resulted in:

No improvement in overall survival (median 65.5 versus 69.2 months without lymphadenectomy; hazard ratio [HR] for death in the lymphadenectomy group 1.06, 95% CI 0.83-1.34)

No improvement in progression-free survival (PFS; median 25.5 months in both groups, HR for death or progression in the lymphadenectomy group 1.11, 95% CI 0.92-1.34)

Longer operative duration (>340 versus >280 minutes)

Increased blood loss (650 versus 500 mL)

Higher transfusion rates (63.7 versus 56.0 percent)

Higher rates of serious postoperative complications (eg, repeat laparotomy for complications: 12.4 versus 6.5 percent)

Higher mortality within 60 days after surgery (3.1 versus 0.9 percent)

Similar measures of quality of life

In contrast to these findings and similar findings from another randomized trial [69], in a third trial in patients with advanced disease (stage IIIB to IV EOC) randomly assigned to undergo either systematic pelvic and paraaortic lymphadenectomy or resection of bulky nodes, systematic lymphadenectomy resulted in an increase in five-year PFS (31.2 versus 21.6 percent) and total PFS (median PFS 29.4 versus 22.4 months, occurrence of first event 0.76, 95% CI 0.60-0.96) [68]. As in the LION trial, there was no difference in five-year overall survival (five-year 49.5 versus 48.0 percent) or total overall survival (median overall survival 62.1 versus 56.3 months, all-cause mortality HR 0.96, 95% CI 0.73-1.26).

Placement of a port for chemotherapy — Some data support a survival advantage in patients with optimally cytoreduced (≤1 cm) stage III epithelial ovarian cancer who are treated with intraperitoneal chemotherapy. The procedure for port placement and this therapy are discussed in detail separately. (See "Intraperitoneal chemotherapy for treatment of ovarian cancer".)

ISSUES RELATED TO NONPRIMARY CYTOREDUCTION

Repeat cytoreduction after suboptimal primary cytoreduction — A repeat attempt at cytoreduction after chemotherapy for suboptimally debulked disease does not provide an outcome that is equivalent to that achieved by aggressive primary surgical debulking followed by paclitaxel and platinum-based combination chemotherapy [70]. However, if the initial surgical attempt at cytoreduction was not a maximal surgical effort, then chemotherapy followed by a repeat attempt at surgical cytoreduction might be beneficial [71]. An example of this situation is when the initial surgery is not performed by a gynecologic oncologist.

The efficacy of repeat cytoreduction after a suboptimal primary resection was addressed in the two large cooperative group randomized trials described below [71,72].

A survival benefit was suggested by the Gynecological Cancer Cooperative Group of the European Organisation for Research and Treatment of Cancer (EORTC) trial in which 319 patients with residual lesions >1 cm in diameter after primary surgery were randomly assigned to receive six cycles of chemotherapy with cyclophosphamide/cisplatin alone or three cycles of chemotherapy followed by repeat cytoreduction and then three more cycles of chemotherapy [71]. Compared with the group who received six cycles of chemotherapy alone, patients who underwent a repeat attempt at debulking had significantly longer disease-free survival and a significant six month prolongation in median survival (26 versus 20 months).

However, the Gynecologic Oncology Group trial (GOG 152) in the United States failed to confirm a survival benefit for repeat cytoreduction [72]. In this trial, 550 patients with suboptimally debulked stage III/IV ovarian cancer and performance status ≥2 received three cycles of paclitaxel/cisplatin and then were randomly assigned to repeat cytoreduction or no surgery. Chemotherapy was continued up to a maximum of six cycles. A repeat attempt at cytoreduction did not result in better overall survival (36.2 versus 35.7 months), disease-free survival (12.5 versus 12.7 months), or quality of life [73].

Important differences between these two large trials are that in the EORTC trial, surgeons other than experienced gynecologic oncologists performed many of the initial procedures, more stage IV patients and patients with poor performance status were included, and cyclophosphamide/cisplatin was used instead of paclitaxel/cisplatin. The most important difference appears to be that patients in the EORTC trial likely underwent less aggressive attempts at primary cytoreduction than those in the GOG trial. The number of patients with <5 cm residual tumor after primary surgery in the EORTC trial was fewer than one-third, compared with 55 percent in the GOG trial.

A systematic review that evaluated these and one other randomized trial and six observational studies of chemotherapy and repeat cytoreduction following a concerted but suboptimal attempt at up-front cytoreduction found no survival benefit for repeat cytoreduction after chemotherapy compared with chemotherapy alone [70].

Interval cytoreduction — Patients undergoing neoadjuvant chemotherapy with subsequent interval cytoreduction are a different group from those undergoing primary, repeat, or secondary/tertiary cytoreduction. However, the surgical procedure for cytoreduction described above and the goal of achieving complete cytoreduction, if possible, are the same. Selection of candidates for neoadjuvant chemotherapy, chemotherapy regimens, timing of surgery, and outcomes, are reviewed separately. (See "Patient selection and approach to neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer".)

Secondary cytoreduction — Candidates for secondary cytoreduction are patients who have undergone primary cytoreduction, developed limited sites of recurrence, and have platinum-sensitive disease (defined as a recurrence beyond six months after completion of adjuvant platinum-based chemotherapy). The efficacy of secondary, and even tertiary, cytoreduction after disease recurrence is reviewed separately. (See "Cancer of the ovary, fallopian tube, and peritoneum: Surgical options for recurrent cancer", section on 'Secondary cytoreductive surgery'.)

POSTOPERATIVE ISSUES

Adjuvant chemotherapy – The majority of patients with EOC benefit from postoperative chemotherapy. It should be started as soon as feasible, usually within two to four weeks after surgery. While there are no high-quality data to inform the optimal timing for the initiation of first-line chemotherapy, limited data suggest that a delay of greater than approximately one month in instituting chemotherapy may be associated with a poorer outcome. Chemotherapy for EOC is discussed separately. (See "Adjuvant therapy of early-stage (stage I and II) epithelial ovarian, fallopian tube, or peritoneal cancer", section on 'Intravenous chemotherapy' and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer", section on 'Timing of treatment initiation'.)

Posttreatment surveillance – (See "Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum", section on 'Posttreatment surveillance' and "Approach to survivors of epithelial ovarian, fallopian tube, or peritoneal carcinoma", section on 'Post-treatment surveillance'.)

Prognosis – (See "Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum", section on 'Prognosis'.)

Other issues – Other posttreatment issues, including management of menopause, menopausal hormone therapy, and sexual health, are discussed separately. (See "Approach to survivors of epithelial ovarian, fallopian tube, or peritoneal carcinoma".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ovarian, fallopian tube, and peritoneal cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Treatment of ovarian cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

The volume of residual disease remaining after cytoreductive surgery correlates inversely with survival (figure 1). Thus, the goal of surgery is to remove all macroscopic disease (ie, complete cytoreduction). Optimal cytoreduction (residual disease ≤1 cm in maximum tumor diameter) is a reasonable option if complete cytoreduction is not possible. Neoadjuvant chemotherapy should be strongly considered for those patients who are not candidates for optimal cytoreduction. (See 'Goal and efficacy' above and 'Terminology' above.)

Factors limiting the ability to achieve optimal cytoreduction may be technical or related to poor performance status. Disease features limiting success include extra-abdominal or extensive retroperitoneal disease, large tumor bulk, bulk disease in the porta hepatis region, extensive bowel involvement, parenchymal liver involvement, or mesenteric root involvement. (See 'Predicting feasibility of cytoreduction' above.)

Imaging and physical examination, and when needed laparoscopic assessment and minilaparotomy, are useful tools for selecting those patients who can be optimally debulked. Providers should utilize findings from these tools for preoperative decision making to reduce the chances of a futile laparotomy. (See 'Predicting feasibility of cytoreduction' above.)

Surgical cytoreduction should be performed by a gynecologic oncologist experienced in this surgery since achieving optimal cytoreduction depends partly on the judgment, experience, skill, and aggressiveness of the surgeon. The surgical team should be prepared to undertake potentially extensive surgery, such as splenectomy, bowel resection, partial hepatectomy, and diaphragmatic resection to achieve an optimal procedure. Such extensive surgery should be utilized only in a setting where optimal cytoreduction is determined feasible. (See 'Cytoreduction procedures' above.)

For patients with stage III or IV disease, we suggest not performing systematic pelvic and paraaortic lymphadenectomy as a routine practice in all patients (Grade 2B). We use a selective approach: if cytoreduction is being attempted, we resect grossly suspicious nodes with the goal of achieving cytoreduction to either no gross residual disease or to ≤1 cm residual disease if resection to no gross residual disease is impossible. However, if complete or optimal cytoreduction is not possible at metastatic sites other than the lymph nodes, we do not remove suspicious lymph nodes. (See 'Lymphadenectomy' above.)

By contrast, for patients with apparent stage I or II disease (disease appears to be limited to the ovaries or pelvis), we perform bilateral lymph node sampling to detect micrometastases that would change the stage. (See 'Lymphadenectomy' above.)

A repeat attempt at cytoreduction after chemotherapy for suboptimally debulked disease does not provide an outcome that is equivalent to that achieved by aggressive primary surgical debulking followed by paclitaxel and platinum-based combination chemotherapy. However, if the initial surgical attempt at cytoreduction was not a maximal surgical effort, then chemotherapy followed by a repeat attempt at surgical cytoreduction might be beneficial. An example of this situation is when the initial surgery is not performed by a gynecologic oncologist. (See 'Repeat cytoreduction after suboptimal primary cytoreduction' above.)

Patients undergoing neoadjuvant chemotherapy with subsequent interval cytoreduction are a different group from those undergoing primary, repeat, or secondary cytoreduction. Selection of candidates for neoadjuvant chemotherapy, chemotherapy regimens, timing of surgery, and outcomes are reviewed separately. (See "Patient selection and approach to neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer".)

Candidates for secondary cytoreduction are patients who have undergone primary cytoreduction, developed limited sites of recurrence, and have platinum-sensitive disease (defined as a recurrence beyond six months after completion of adjuvant platinum-based chemotherapy). (See "Cancer of the ovary, fallopian tube, and peritoneum: Surgical options for recurrent cancer".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges William Mann, Jr., MD; Eva Chalas, MD, FACOG, FACS; Fidel Valea, MD; and Heidi Gray, MD, who contributed to earlier versions of this topic review.

  1. Merogi AJ, Marrogi AJ, Ramesh R, et al. Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. Hum Pathol 1997; 28:321.
  2. Woo EY, Chu CS, Goletz TJ, et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 2001; 61:4766.
  3. Santin AD, Hermonat PL, Ravaggi A, et al. Secretion of vascular endothelial growth factor in ovarian cancer. Eur J Gynaecol Oncol 1999; 20:177.
  4. Hoskins WJ, McGuire WP, Brady MF, et al. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol 1994; 170:974.
  5. Eisenkop SM, Friedman RL, Wang HJ. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study. Gynecol Oncol 1998; 69:103.
  6. Allen DG, Heintz AP, Touw FW. A meta-analysis of residual disease and survival in stage III and IV carcinoma of the ovary. Eur J Gynaecol Oncol 1995; 16:349.
  7. Chi DS, Eisenhauer EL, Lang J, et al. What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol 2006; 103:559.
  8. Winter WE 3rd, Maxwell GL, Tian C, et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25:3621.
  9. Wimberger P, Lehmann N, Kimmig R, et al. Prognostic factors for complete debulking in advanced ovarian cancer and its impact on survival. An exploratory analysis of a prospectively randomized phase III study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol 2007; 106:69.
  10. Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002; 20:1248.
  11. Teramukai S, Ochiai K, Tada H, et al. PIEPOC: a new prognostic index for advanced epithelial ovarian cancer--Japan Multinational Trial Organization OC01-01. J Clin Oncol 2007; 25:3302.
  12. Chang SJ, Hodeib M, Chang J, Bristow RE. Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: a meta-analysis. Gynecol Oncol 2013; 130:493.
  13. Hoskins WJ. Epithelial ovarian carcinoma: principles of primary surgery. Gynecol Oncol 1994; 55:S91.
  14. Eisenkop SM, Spirtos NM, Lin WC. "Optimal" cytoreduction for advanced epithelial ovarian cancer: a commentary. Gynecol Oncol 2006; 103:329.
  15. Winter WE 3rd, Maxwell GL, Tian C, et al. Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2008; 26:83.
  16. Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al. The effect of maximal surgical cytoreduction on sensitivity to platinum-taxane chemotherapy and subsequent survival in patients with advanced ovarian cancer. Gynecol Oncol 2008; 108:276.
  17. Covens AL. A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol 2000; 78:269.
  18. Elattar A, Bryant A, Winter-Roach BA, et al. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2011; :CD007565.
  19. Hiu S, Bryant A, Gajjar K, et al. Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2022; 8:CD007697.
  20. Rutten MJ, van Meurs HS, van de Vrie R, et al. Laparoscopy to Predict the Result of Primary Cytoreductive Surgery in Patients With Advanced Ovarian Cancer: A Randomized Controlled Trial. J Clin Oncol 2017; 35:613.
  21. Axtell AE, Lee MH, Bristow RE, et al. Multi-institutional reciprocal validation study of computed tomography predictors of suboptimal primary cytoreduction in patients with advanced ovarian cancer. J Clin Oncol 2007; 25:384.
  22. Yazdi GP, Miedema BW, Humphrey LJ. High mortality after abdominal operation in patients with large-volume malignant ascites. J Surg Oncol 1996; 62:93.
  23. Vergote I, de Wever I, Tjalma W, et al. Interval debulking surgery: an alternative for primary surgical debulking? Semin Surg Oncol 2000; 19:49.
  24. Tamussino KF, Lim PC, Webb MJ, et al. Gastrointestinal surgery in patients with ovarian cancer. Gynecol Oncol 2001; 80:79.
  25. Aletti GD, Gostout BS, Podratz KC, Cliby WA. Ovarian cancer surgical resectability: relative impact of disease, patient status, and surgeon. Gynecol Oncol 2006; 100:33.
  26. Eltabbakh GH, Mount SL, Beatty B, et al. Factors associated with cytoreducibility among women with ovarian carcinoma. Gynecol Oncol 2004; 95:377.
  27. Gilani MM, Karimi Zarchi M, Ghaemmaghami F, et al. A study to evaluate the utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer. Gynecol Oncol 2007; 105:780.
  28. Kang S, Kim TJ, Nam BH, et al. Preoperative serum CA-125 levels and risk of suboptimal cytoreduction in ovarian cancer: a meta-analysis. J Surg Oncol 2010; 101:13.
  29. Salani R, Axtell A, Gerardi M, et al. Limited utility of conventional criteria for predicting unresectable disease in patients with advanced stage epithelial ovarian cancer. Gynecol Oncol 2008; 108:271.
  30. Qayyum A, Coakley FV, Westphalen AC, et al. Role of CT and MR imaging in predicting optimal cytoreduction of newly diagnosed primary epithelial ovarian cancer. Gynecol Oncol 2005; 96:301.
  31. Risum S, Høgdall C, Loft A, et al. Prediction of suboptimal primary cytoreduction in primary ovarian cancer with combined positron emission tomography/computed tomography--a prospective study. Gynecol Oncol 2008; 108:265.
  32. Fagotti A, Ferrandina G, Fanfani F, et al. A laparoscopy-based score to predict surgical outcome in patients with advanced ovarian carcinoma: a pilot study. Ann Surg Oncol 2006; 13:1156.
  33. Chi DS, Franklin CC, Levine DA, et al. Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach. Gynecol Oncol 2004; 94:650.
  34. Aletti GD, Dowdy SC, Gostout BS, et al. Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Obstet Gynecol 2006; 107:77.
  35. Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al. The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages IIIC-IV epithelial ovarian cancer. Gynecol Oncol 2006; 103:1083.
  36. Chi DS, Eisenhauer EL, Zivanovic O, et al. Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol 2009; 114:26.
  37. Chi DS, Zivanovic O, Levinson KL, et al. The incidence of major complications after the performance of extensive upper abdominal surgical procedures during primary cytoreduction of advanced ovarian, tubal, and peritoneal carcinomas. Gynecol Oncol 2010; 119:38.
  38. Bristow RE, Montz FJ. Complete surgical cytoreduction of advanced ovarian carcinoma using the argon beam coagulator. Gynecol Oncol 2001; 83:39.
  39. Eisenkop SM, Nalick RH, Wang HJ, Teng NN. Peritoneal implant elimination during cytoreductive surgery for ovarian cancer: impact on survival. Gynecol Oncol 1993; 51:224.
  40. van Dam PA, Tjalma W, Weyler J, et al. Ultraradical debulking of epithelial ovarian cancer with the ultrasonic surgical aspirator: a prospective randomized trial. Am J Obstet Gynecol 1996; 174:943.
  41. Rose PG. The cavitational ultrasonic surgical aspirator for cytoreduction in advanced ovarian cancer. Am J Obstet Gynecol 1992; 166:843.
  42. Fanning J, Hilgers RD, Richards PK, Hunt KD. Carbon dioxide laser vaporization of intestinal metastases of epithelial ovarian cancer. Int J Gynecol Cancer 1994; 4:324.
  43. Patsner B. Carbon dioxide laser vaporization of diaphragmatic metastases for cytoreduction of ovarian epithelial cancer. Obstet Gynecol 1990; 76:724.
  44. Voelker R. Lighting the Way for Improved Detection of Ovarian Cancer. JAMA 2022; 327:27.
  45. https://www.fda.gov/news-events/press-announcements/fda-approves-new-imaging-drug-help-identify-ovarian-cancer-lesions (Accessed on December 06, 2021).
  46. https://cytalux.com/wp-content/uploads/2021/11/CYTALUX-Prescribing-Information.pdf (Accessed on December 06, 2021).
  47. Randall LM, Wenham RM, Low PS, et al. A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecol Oncol 2019; 155:63.
  48. Tanyi JL, Randall LM, Chambers SK, et al. A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006). J Clin Oncol 2023; 41:276.
  49. Scholz HS, Tasdemir H, Hunlich T, et al. Multivisceral cytoreductive surgery in FIGO stages IIIC and IV epithelial ovarian cancer: results and 5-year follow-up. Gynecol Oncol 2007; 106:591.
  50. Eisenkop SM, Spirtos NM, Lin WC. Splenectomy in the context of primary cytoreductive operations for advanced epithelial ovarian cancer. Gynecol Oncol 2006; 100:344.
  51. Magtibay PM, Adams PB, Silverman MB, et al. Splenectomy as part of cytoreductive surgery in ovarian cancer. Gynecol Oncol 2006; 102:369.
  52. Bristow RE, Montz FJ, Lagasse LD, et al. Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer. Gynecol Oncol 1999; 72:278.
  53. Liu PC, Benjamin I, Morgan MA, et al. Effect of surgical debulking on survival in stage IV ovarian cancer. Gynecol Oncol 1997; 64:4.
  54. Chi DS, Temkin SM, Abu-Rustum NR, et al. Major hepatectomy at interval debulking for stage IV ovarian carcinoma: a case report. Gynecol Oncol 2002; 87:138.
  55. Cliby W, Dowdy S, Feitoza SS, et al. Diaphragm resection for ovarian cancer: technique and short-term complications. Gynecol Oncol 2004; 94:655.
  56. Kapnick SJ, Griffiths CT, Finkler NJ. Occult pleural involvement in stage III ovarian carcinoma: role of diaphragm resection. Gynecol Oncol 1990; 39:135.
  57. Montz FJ, Schlaerth JB, Berek JS. Resection of diaphragmatic peritoneum and muscle: role in cytoreductive surgery for ovarian cancer. Gynecol Oncol 1989; 35:338.
  58. Tsolakidis D, Amant F, Van Gorp T, et al. Diaphragmatic surgery during primary debulking in 89 patients with stage IIIB-IV epithelial ovarian cancer. Gynecol Oncol 2010; 116:489.
  59. Fanfani F, Fagotti A, Gallotta V, et al. Upper abdominal surgery in advanced and recurrent ovarian cancer: role of diaphragmatic surgery. Gynecol Oncol 2010; 116:497.
  60. Aletti GD, Dowdy SC, Podratz KC, Cliby WA. Surgical treatment of diaphragm disease correlates with improved survival in optimally debulked advanced stage ovarian cancer. Gynecol Oncol 2006; 100:283.
  61. Scarabelli C, Gallo A, Franceschi S, et al. Primary cytoreductive surgery with rectosigmoid colon resection for patients with advanced epithelial ovarian carcinoma. Cancer 2000; 88:389.
  62. O'Hanlan KA, Kargas S, Schreiber M, et al. Ovarian carcinoma metastases to gastrointestinal tract appear to spread like colon carcinoma: implications for surgical resection. Gynecol Oncol 1995; 59:200.
  63. Weber AM, Kennedy AW. The role of bowel resection in the primary surgical debulking of carcinoma of the ovary. J Am Coll Surg 1994; 179:465.
  64. Mourton SM, Temple LK, Abu-Rustum NR, et al. Morbidity of rectosigmoid resection and primary anastomosis in patients undergoing primary cytoreductive surgery for advanced epithelial ovarian cancer. Gynecol Oncol 2005; 99:608.
  65. Tebes SJ, Cardosi R, Hoffman MS. Colorectal resection in patients with ovarian and primary peritoneal carcinoma. Am J Obstet Gynecol 2006; 195:585.
  66. Kingham TP, Pachter HL. Colonic anastomotic leak: risk factors, diagnosis, and treatment. J Am Coll Surg 2009; 208:269.
  67. Harter P, Sehouli J, Lorusso D, et al. A Randomized Trial of Lymphadenectomy in Patients with Advanced Ovarian Neoplasms. N Engl J Med 2019; 380:822.
  68. Panici PB, Maggioni A, Hacker N, et al. Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial. J Natl Cancer Inst 2005; 97:560.
  69. Maggioni A, Benedetti Panici P, Dell'Anna T, et al. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis. Br J Cancer 2006; 95:699.
  70. Bristow RE, Eisenhauer EL, Santillan A, Chi DS. Delaying the primary surgical effort for advanced ovarian cancer: a systematic review of neoadjuvant chemotherapy and interval cytoreduction. Gynecol Oncol 2007; 104:480.
  71. van der Burg ME, van Lent M, Buyse M, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 1995; 332:629.
  72. Rose PG, Nerenstone S, Brady MF, et al. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med 2004; 351:2489.
  73. Wenzel L, Huang HQ, Monk BJ, et al. Quality-of-life comparisons in a randomized trial of interval secondary cytoreduction in advanced ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2005; 23:5605.
Topic 122088 Version 17.0

References

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