Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Practice Guidelines The role of laparoscopy in the evaluation and treatment of epithelial ovarian cancer J. Hauspy, B. Pouseele, J. Van Wiemeersch, A. Rutten, L. Verkinderen, P.A. Van Dam Laparotomy has been the standard approach for diagnosis and treatment of ovarian cancer. The goal of this article was to collect and summarise the evidence concerning the use of laparoscopy in ovarian cancer. We performed a Medline search of studies and reviews about the laparoscopic approach for evaluation of surgery of ovarian cancer. Laparoscopy appears to be a safe, accurate and patient-friendly alternative for laparotomy in primary surgery for early-stage ovarian cancer and in accurate staging and evaluation of operability in advanced ovarian cancer. Very little evidence is available on the role of laparoscopy in advanced ovarian cancer. Belg J Med Oncol 2012;6:157-163) Introduction Approximately 25-30% of patients with ovarian cancer present with early stage disease, limited to the gynaecological organs and not spread to adjacent structures in the pelvis or the upper abdomen.1,2 The majority of ovarian cancer patients are diagnosed in an advanced stage for which the standard approach is surgical exploration of the abdomen with the aim of achieving maximal cytoreduction at the end of the surgery. Since 2010 it has been shown that neo-adjuvant chemotherapy followed by interval debulking has an equal disease-free survival (DFS) and overall survival (OS) outcome for inoperable advanced disease, but reduces the complications and extent of the surgery.3 In the patients’ interest it is important to evaluate the possibility of maximal cytoreduction prior to surgery. Imaging techniques including MRI, CT and Ultrasound, have proven to be poor indicators of optimal debulkability. Only the last decades, the laparoscopic approach has been introduced in the diagnosis and treatment of ovarian tumours suspected of malignancy. The first authors to report on the use of laparoscopy in ovarian cancer were Bagley et al. in 1973.4 The International Federation of Gynecology and Obstetrics (FIGO) indicates three mayor independent factors for prognosis of ovarian cancer: stage at diagnosis, histological grade and residual tumour after surgery.5 Laparoscopy has become the standard procedure for benign ovarian surgery, and several studies have demonstrated that laparoscopic treatment of patients Authors: J. Hauspy, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA Hospitals, Wilrijk, Belgium; J. Van Wiemeersch, Department of Obstetrics and Gynaecology, GZA Hospitals, Wilrijk, Belgium; A. Rutten, Department of Medical Oncology, GZA Hospitals, Wilrijk, Belgium; L. Verkinderen, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA Hospitals, Wilrijk, Belgium; P.A. Van Dam, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA Hospitals, Wilrijk, Belgium. Please send all correspondence to: J. Hauspy, Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, GZA hospitals campus Sint Augustinus, Oosterveldlaan 24, 2610 Wilrijk, Belgium. Conflict of interest: the authors have nothing to disclose and indicate no conflicts of interest. Keywords: ovarian cancer, laparoscopy, minimally invasive surgery. Belgian Journal of Medical Oncology 157 volume 6, issue 5, 2012 ovarian mass ultrasound benign aspect laparoscopic evaluation benign aspect laparoscopic adnexectomy or ovarian cystectomy suspicious for malignancy laparoscopy (frozen section) suspicious for malignancy apparent early stage ovarian cancer advanced ovarian cancer laparoscopic staging operation* debulking surgery vs neoadjuvant chemotherapy** Figure 1. Decision diagram for laparoscopy in ovarian cancer: * includes hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, omentectomy and multiple peritoneal biopsies ** laparoscopy to evaluate the feasibility of primary debulking surgery versus neoadjuvant chemotherapy with interval debulking. with other gynaecological malignancies is equivalent to traditional surgery, with clear benefits such as better visualisation, lower morbidity, less pain, a shorter hospital stay, a lower risk of postoperative infection and better cosmetic results.6-8 In general, laparoscopy appears to induce less morbidity, shortens hospital stay due to a faster recovery and produces a better cosmetic result compared to laparotomy. Immediate costs related to the surgery appear to be higher for laparoscopic interventions when compared to open surgery, due to disposable instrument costs in the operating room. However, taking other factors into account, such as hospital stay, postoperative medication and investigations, rehabilitation and lost productivity, laparoscopy proves to be very cost-efficient. Pre-operative assessment of the ovarian mass The most widely used ultrasound methods to classify an ovarian mass are the risk of malignancy index (RMI) and the risk of ovarian malignancy algorithm (ROMA).9,10 The RMI is based on three criteria: serum CA125 level (U/ml), the ultrasound scan result (expressed as a score of 0, 1 or 3) and the menopausal status (1 if premenopausal and 3 if postmenopausal). The RMI is simply calculated using the product of these parameters (Figure 1). Using a RMI cut-off level of 200, the sensitivity in the original study of Jacobs was 85% and the specificity was 97%. Patients with a RMI score over 200 had, on average, 42 times the background risk of cancer and those with a lower value 0.15 times the background risk.9 Belgian Journal of Medical Oncology volume 6, issue 5, 2012 158 5 Practice Guidelines In 2009, Moore et al presented a new algorithm, the ROMA, which is based on both CA125 and human epididymis secretory protein 4 (HE4).11 By this method, patients are classified into high and low risk groups. In the original article, 93.8% of ovarian cancers were correctly classified as high-risk. One year later, they presented a study comparing ROMA to RMI. Their conclusion was that the ROMA method achieves a significantly higher sensitivity for identifying women with ovarian cancer than RMI.12 A very recent study performed by Van Gorp and his colleagues compared the ROMA system to the RMI method and with subjective assessment by ultrasound.10 They concluded that, although new tumour marker models are promising, they do not contribute significantly to the diagnosis of ovarian cancer. Ultrasound, especially subjective assessment by ultrasound, remains superior in discriminating malignant from benign ovarian masses. Early-stage ovarian cancer Early-stage ovarian cancer accounts for 25-30% of all ovarian cancer cases, and has a good prognosis with five-year survival rates that vary between 75% and 85%.1,2 Diagnosis of ovarian cancer at an early stage is difficult. In most cases, early-stage disease is incidentally found by laparoscopic salpingooophorectomy for a presumed benign ovarian cyst.8 Accurate staging is crucial for optimal and correct adjuvant treatment of ovarian cancer. Disease upstaging does not only have implications in providing correct prognostic information, it also affects indications for adjuvant therapy and may ultimately result Table 1. Jacobs Risk of Malignancy Index.9 RMI = CA 125 (U/ml) x menopausal state x ultrasound score menopausal status: - premenopausal = 1 - postmenopausal = 3 ultrasound score criteria: - multilocular - solid parts - ascites - bilateral - intra-abdominal metastases no criteria = score 0 one criterium = score 1 two or more criteria = score 3 in an improved DFS and OS. A European Organization for Research and Treatment of Cancer (EORTC) study in 2003 showed that patients with occult residual disease benefit from adjuvant chemotherapy, increasing the DFS and OS.2 If staging is suboptimal, this could lead to residual tumour and undertreatment with a worse outcome. Proper staging of an incidentally found -presumed early stage- ovarian cancer should be performed in all patients. Further staging should include peritoneal washings, hysterectomy and contralateral oophorectomy as well as omentectomy, pelvic and para-aortic lymph node dissection and multiple peritoneal biopsies as well as thorough inspection of the entire abdominal cavity. In most patients this procedure can be performed laparoscopically.13,14 In 2006, Lécuru and his colleagues performed a retrospective review of patients with stage I ovarian cancer.1 They compared staging and survival in patients with laparoscopy versus laparotomy as the first surgical access. The study did not find any harmful influence of laparoscopy as first initial access on the outcome in this group of patients. Careful inspection of the entire abdomen, including large and small intestines should be performed. For a thorough inspection of the liver surface and diaphragm, the use of a 30-degree laparoscope is often required. A recent study compared surgical outcomes, complications and costs between laparotomy and laparoscopy in early-stage ovarian cancer.8 The laparoscopy group had less perioperative complications, less intraoperative blood loss, less transfusion requirement, shorter hospital stay, less postoperative pain and a shorter time to adjuvant chemotherapy compared to the laparotomy group. Operative time was comparable, but costs for laparoscopy were significantly higher than those for laparotomic staging surgery. One of the concerns in laparoscopic treatment of early-stage ovarian cancer is the risk of intraoperative rupture of the adnexal mass with tumour spilling. Therefore careful extraction of any ovarian mass using a laparoscopic bag is always indicated. Advanced Stage Ovarian Cancer The majority of women diagnosed with ovarian cancer present with advanced intra-abdominal disease, and subsequently a low cure rate. Since Griffiths published his article in 1975, we know Belgian Journal of Medical Oncology 159 volume 6, issue 5, 2012 that the amount of residual tumour after primary cytoreductive surgery is one of the most important factors for DFS and OS of these patients.15 Optimal debulking is now considered to leave no residual laesions larger than 1cm in diameter after primary surgery, but even better outcomes have been reported if no visible disease is present at the end of surgical cytoreduction.16 Success rates of achieving optimal cytoreductive surgery vary between reporting institutions, but generally do not exceed 50%, even in the hands of experienced oncological surgeons.17 Primary cytoreductive surgery by laparotomy is considered the standard of care for advanced ovarian carcinoma.3 Diagnostic laparoscopy in advanced disease has a lot of theoretical advantages: magnification of the pelvic and abdominal anatomy, enhanced visualisation of metastases of the upper abdomen, surface of the liver and diaphragm.17 Besides, imaging techniques such as CT-scan, ultrasound, MRI and PET-scan have failed to accurately assess the potential for optimal cytoreduction in advanced ovarian cancer.18,19 Of all these techniques, PET/CT has proven to be the most accurate.18 Knowing that the amount of residual tumour has a strong prognostic impact, patients with initial unresectable disease have been successfully treated with neoadjuvant chemotherapy followed by interval debulking.3,20 This leads to fewer peri- and postoperative complications and better optimal debulking rates. Diagnostic laparoscopy is a useful tool in the evaluation of patients suspected for unresectable disease.17,21 By avoiding a laparotomy, recovery is faster and chemotherapy can be started quicker. Vergote et al reported the results of an EORTC study comparing primary debulking and neoadjuvant chemotherapy.3 Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma. Abdominal wall metastases When using laparoscopy in oncological surgery, one must ascertain safety issues of iatrogenic disease spread. Spread of cancer cells is facilitated by the use of CO2, creating a pressure gradient with a chimney effect , floating tumour cells through the port wounds.6 Likewise, removal of tumour-loaded specimens can provoke implantation of cells at the wounds. The chimney effect and tumour removal can cause port sites to be contaminated with tumour cells. Heitz et al reported a retrospective study of 537 patients with a first diagnosis of ovarian cancer.22 They investigated the incidence, risk factors and complications of abdominal wall metastases after laparoscopy conducted before cytoreductive surgery. The incidence of abdominal wall metastasis was considerably high: 47% of investigated patients had histological proven port metastasis. However, there was no impact on survival. This incidence was much higher than the earlier reported incidence of 0 to 21%, probably due to selection of patients with more advanced disease and to the rather long period between laparoscopy and cytoreductive therapy.23,24 Also, the diagnosis was based on histopathology of all trocar sites, and not only on clinical metastasis. In this way, subclinical metastases were also diagnosed. Van Dam et al investigated the difference in closing of the laparoscopy ports.25 A recurrence developed at the trocar site in 58% of patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in only 2% of patients undergoing a laparoscopy with closure of all layers. Second-look laparoscopy Although the indications remain controversial, second-look laparotomies have been performed since decades to evaluate the effect of chemotherapy in advanced ovarian cancers. Despite initial good response to chemotherapy, the majority of patients with advanced ovarian cancer will eventually die of their disease. Approximately 50% of patients with negative second-look laparotomy will eventually develop recurrent disease, so it must be assumed that all these patients have microscopic disease. Nevertheless, the subgroup of patients with a negative second-look operation has a better prognosis with continued chemotherapy.26 The accuracy and safety of second-look laparoscopy was investigated in several studies, and seemed similar to laparotomy.26-28 Sometimes the procedure can be difficult because of severe postoperative adhesions, which makes visualisation of the whole peritoneal cavity impossible and gives a higher risk of perioperative complications. Belgian Journal of Medical Oncology volume 6, issue 5, 2012 160 5 Practice Guidelines Littell et al studied the negative predictive value of second-look laparoscopy compared to laparotomy for assessment of pathological complete response in patients who achieved a clinical complete remission.28 Their conclusion was that a negative second-look laparoscopy with negative peritoneal pathology and cytology is 91.5% predictive of negative laparotomy and is associated with a low complication rate even in the setting of prior extensive surgery. In their study, laparotomy thus had a slightly higher sensitivity and negative predictive value, but this does not warrant the increased morbidity. Borderline ovarian cancer Borderline tumours of the ovary account for 15% of all epithelial ovarian tumours. Because of their slow growth and limited potential to metastasise, they are generally detected at an early stage and have a good prognosis with an overall recurrence rate of 10-20%. However, recurrence rates of FIGO stages II and III borderline ovarian tumours can be as high as 30% with a median time to recurrence of 5-7 years.29 Maneo and his colleagues analysed 62 patients with a borderline ovarian tumour, 30 were operated on laparoscopically, 32 by laparotomy.30 They concluded that the diameter of the cyst is a significant factor to predict failure of laparoscopy, with a bigger risk of rupture or persistence of the tumour in masses larger than 5cm. The use of lymph node dissections in borderline ovarian tumours is limited. It is however important to perform a thorough inspection of the entire abdomen as well as an omentectomy and multiple peritoneal biopsies. A small number of patients with serous borderline ovarian tumours, present with tumoural implants which can be found throughout the abdomen and in the omentum. Rarely, these implants consist of invasive tumour cells, in which case adjuvant systemic treatment is recommended. However, given the rarity of these occurrences, no randomised controlled trials are available to support this treatment approach. Robotic surgery The experience with robotic surgery in ovarian cancer is very limited, and the use of robotics in ovari- an tumours should be considered as experimental. Recently, Magrina et al published a series of 25 patients who underwent robot-assisted surgical treatment.31 The results were compared to laparoscopic and laparotomic approach. They concluded that laparoscopy and robotic surgery are preferable to laparotomy for early-stage ovarian cancer. They could not prove any significant benefit of robotics compared to laparoscopy. One can assume that the advantages found by laparoscopy will be similar when using robot-assisted surgery. The first reports comparing all three techniques are being presented currently, although prospective trials are lacking. Conclusion Although tumour marker models are promising, until now they do not contribute significantly to the preoperative assessment of ovarian cancer. Ultrasound evaluation remains the most reliable investigation, together with PET/CT scan. The use of laparoscopy as first surgical access in ovarian cancer increases the diagnostic power, allowing a more accurate staging. For selected patients with early-stage ovarian cancer, laparoscopic staging surgery is therefore a good alternative to laparotomy. It results in less postoperative pain, shorter hospital stay, faster recovery and better cosmetic results. Laparoscopic treatment should be performed by experienced laparoscopic surgeons, to minimalise intraoperative spilling and avoid understaging. In case of intraoperative rupture of the tumour, a careful pelvic washing should be performed. Manipulation of the tumour should be kept to a minimum, and any biopsy specimen should be extracted with a laparoscopic bag to avoid abdominal wall metastases. In advanced disease, laparoscopy can safely be used to evaluate the feasibility of complete debulking and accurately assess patients with no or very difficult primary resectable disease who might benefit from neoadjuvant chemotherapy. The risk of abdominal wall metastases appears to be higher after laparoscopy in advanced ovarian cancer and in the presence of ascites, but the risk can be reduced by closure of all layers. Abdominal wall metastases appear to have no influence on longterm outcome. If there is indication for second-look to evaluate complete remission, laparoscopy is preferred to Belgian Journal of Medical Oncology 161 volume 6, issue 5, 2012 Key messages for clinical practice • Laparoscopic surgical staging for ovarian cancer is safe. • It is at least as adequate as surgical staging by laparotomy. • Also, early-stage ovarian cancer can safely be treated by laparoscopy alone in most cases. • Currently, debulking surgery by laparoscopy for advanced ovarian cancer is not recommended. laparotomy because of the lower morbidity. The use of robotic surgery in ovarian cancer is promising, but should be used with caution in the absence of data showing non-inferiority to laparoscopy. 9. Jacobs I, Oram D, Fairbanks J, et al. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. British journal of obstetrics and gynaecology 1990;97:922-9. 10.Van Gorp T, Veldman J, Van Calster B, et al. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of References ovarian malignancy algorithm (ROMA) in discriminating benign from malignant 1. Lécuru F, Desfeux P, Camatte S, et al. Impact of initial surgical access on adnexal masses. European journal of cancer 2012. staging and survival in patients with stage I ovarian cancer. International 11.Moore RG, McMeekin DS, Brown AK, et al. A novel multiple marker journal of gynecological cancer : official journal of the International Gyneco- bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in logical Cancer Society 2006;16:87-94. patients with a pelvic mass. Gynecologic oncology 2009;112:40-6. 2. Trimbos JB, Vergote I, Bolis G, et al. Impact of adjuvant chemotherapy 12.Moore RG, Jabre-Raughley M, Brown AK, et al. Comparison of a novel and surgical staging in early-stage ovarian carcinoma: European Organisation multiple marker assay vs the Risk of Malignancy Index for the prediction of for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian epithelial ovarian cancer in patients with a pelvic mass. American journal of Neoplasm trial. Journal of the National Cancer Institute 2003;95:113-25. obstetrics and gynecology 2010;203:228 e1-6. 3. Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or 13.Mangioni C, Bolis G, Molteni P, et al. Indications, advantages, and limits primary surgery in stage IIIC or IV ovarian cancer. The New England journal of laparoscopy in ovarian cancer. Gynecologic oncology 1979;7:47-55. of medicine 2010;363:943-53. 14.Lehner R, Wenzl R, Heinzl H, et al. Influence of delayed staging laparot- 4. Bagley CM, Young RC, Schein PS, et al. Ovarian carcinoma metastatic omy after laparoscopic removal of ovarian masses later found malignant. to the diaphragm--frequently undiagnosed at laparotomy. A preliminary Obstetrics and gynecology 1998;92:967-71. report. American journal of obstetrics and gynecology 1973;116:397-400. 15.Griffiths CT. Surgical resection of tumour bulk in the primary treatment 5. Benedet JL, Bender H, Jones H III, et al S. FIGO staging classifications of ovarian carcinoma. National Cancer Institute monograph 1975;42:101-4. and clinical practice guidelines in the management of gynecologic cancers. 16.Aletti G, Dowdy S, Gostout B, et al. Aggressive surgical effort and FIGO Committee on Gynecologic Oncology. International journal of gynae- improved survival in advanced-stage ovarian cancer. Obstetrics and gyne- cology and obstetrics: the official organ of the International Federation of cology 2006;107:77-85. Gynaecology and Obstetrics 2000;70:209-62. 17.Angioli R, Palaia I, Zullo MA, et al. Diagnostic open laparoscopy in the 6. Tozzi R, Kohler C, Ferrara A, et al. Laparoscopic treatment of early management of advanced ovarian cancer. Gynecologic oncology ovarian cancer: surgical and survival outcomes. Gynecologic oncology 2006;100:455-61. 2004;93:199-203. 18.Nam EJ, Yun MJ, Oh YT, et al. Diagnosis and staging of primary ovarian 7. Mourits J, Bijen C, Arts H, et al. Safety of laparoscopy versus laparotomy cancer: correlation between PET/CT, Doppler US, and CT or MRI. Gyneco- in early-stage endometrial cancer: a randomised trial. Lancet Oncol logic oncology 2010;116:389-94. 2010;11:763-71. 19. Togashi K. Ovarian cancer: the clinical role of US, CT, and MRI. European 8. Lee M, Kim SW, Paek J, et al. Comparisons of surgical outcomes, com- radiology 2003;13 Suppl 4:L87-104. plications, and costs between laparotomy and laparoscopy in early-stage 20.Fanfani F, Ferrandina G, Corrado G, et al. Impact of interval debulking ovarian cancer. International journal of gynecological cancer : official journal surgery on clinical outcome in primary unresectable FIGO stage IIIc ovarian of the International Gynecological Cancer Society 2011;21:251-6. cancer patients. Oncology 2003;65:316-22. Belgian Journal of Medical Oncology volume 6, issue 5, 2012 162 5 Practice Guidelines 21.Fagotti A, Fanfani F, Ludovisi M, et al. Role of laparoscopy to assess reduced? American journal of obstetrics and gynecology 1999;181:536-41. the chance of optimal cytoreductive surgery in advanced ovarian cancer: 26.Husain A, Chi DS, Prasad M, et al. The role of laparoscopy in second- a pilot study. Gynecologic oncology 2005;96:729-35. look evaluations for ovarian cancer. Gynecologic oncology 2001;80:44-7. 22.Heitz F, Ognjenovic D, Harter P, et al. Abdominal wall metastases in 27. Clough K, Ladonne J, Nos C, Renolleau C, Validire P, Durand J. Second patients with ovarian cancer after laparoscopic surgery: incidence, risk factors, look for ovarian cancer: laparoscopy or laparotomy? A prospective compar- and complications. International journal of gynecological cancer: official ative study. Gynecologic oncology 1999;72:411-7. journal of the International Gynecological Cancer Society 2010;20:41-6. 28.Littell RD, Hallonquist H, Matulonis U, et al Negative laparoscopy is 23.Kruitwagen RF, Swinkels BM, Keyser KG, et al. Incidence and effect on highly predictive of negative second-look laparotomy following chemother- survival of abdominal wall metastases at trocar or puncture sites following apy for ovarian, tubal, and primary peritoneal carcinoma. Gynecologic laparoscopy or paracentesis in women with ovarian cancer. Gynecologic oncology 2006;103:570-4. oncology 1996;60:233-7. 29.Gershenson DMW, Gore M, Thomas G. Gynecologic Cancer.: Elsevier 24.Vergote I, Marquette S, Amant F, et al. Port-site metastases after open Ltd; 2004. laparoscopy: a study in 173 patients with advanced ovarian carcinoma. 30.Maneo A, Vignali M, Chiari S, et al. Are borderline tumours of the ovary International journal of gynecological cancer: official journal of the Interna- safely treated by laparoscopy? Gynecologic oncology 2004;94:387-92. tional Gynecological Cancer Society 2005;15:776-9. 31.Magrina JF, Zanagnolo V, Noble BN, et al. Robotic approach for ovarian 25.Van Dam PA, DeCloedt J, Tjalma WA, et al. Trocar implantation metasta- cancer: perioperative and survival results and comparison with laparoscopy sis after laparoscopy in patients with advanced ovarian cancer: can the risk be and laparotomy. Gynecologic oncology 2011;121:100-5. Belgian Journal of Medical Oncology 163 volume 6, issue 5, 2012