Clinical Study Received: January 7, 2015 Accepted after revision: March 5, 2015 Published online: May 1, 2015
Oncology DOI: 10.1159/000381462
Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy Giovanni Favero a, e Nathalia Macerox d Tatiana Pfiffer a, e Christhardt Köhler e Vanessa da Costa Miranda b Maria Del Pilar Estevez Diz b Julia Tizue Fukushima c Edmund Chada Baracat a Jesus Paula Carvalho a
Departments of a Gynecology and b Medical Oncology, and c Division of Medical Statistics, Instituto do Câncer do Estado de São Paulo – ICESP, Faculdade de Medicina da Universidade de São Paulo, and d Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; e Department of Advanced Gynecologic Surgery and Oncology, Asklepios Hospital Hamburg, Hamburg, Germany
Abstract Background: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. Objectives: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. Methods: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA125 normalization, imaging without disease in critical areas, and optimal cytoreduction. Results: From January 2011 to
© 2015 S. Karger AG, Basel 0030–2414/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/ocl
March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapyfree interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). Conclusion: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results. © 2015 S. Karger AG, Basel
Dr. Giovanni Favero, Department of Gynecology Instituto do Câncer do Estado de São Paulo – ICESP Faculdade de Medicina da Universidade de São Paulo Av. Dr. Enéas Carvalho de Aguiar 255, 10th Floor, 05403-000 São Paulo, SP (Brazil) E-Mail gdifavero @ hotmail.com
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 4:45:13 PM
Key Words Advanced ovarian cancer · Neoadjuvant chemotherapy · Laparoscopic cytoreduction
In developed countries, ovarian cancer is the second most frequent cancer of the female genital tract and is certainly the most lethal [1]. The incidence and the mortality related to this neoplasm in underprivileged regions have significantly increased over the last decades, and it will certainly constitute a major health care problem in the near future [2]. It is estimated that 125,000 women worldwide die each year due to this condition [3]. Despite a number of screening efforts, approximately 75% of patients are diagnosed with advanced forms of the disease (advanced ovarian cancer, AOC) [4]. Surgery represents the cornerstone of treatment for this condition, and diverse studies have clearly demonstrated that achievement of complete cytoreduction (no macroscopic residual tumor) has a substantial impact on survival [5, 6]. Unfortunately, due to the magnitude of disease dissemination, only in about 20–50% of the patients with AOC is primary optimal debulking surgery technically possible [4, 6, 7]. In this scenario, alternative strategies such as neoadjuvant chemotherapy (NACT), leading to higher rates of adequate resection, may be beneficial to a number of patients who are initially considered inoperable [4, 8]. Operative treatment for gynecologic tumors has historically been performed via laparotomy. Over the last decades, minimally invasive surgery has progressively gained popularity in this particular field. Indeed, laparoscopy significantly reduces procedure-related morbidity [9]. On the other hand, several important oncologic concerns have limited the widespread use of laparoscopy especially in ovarian cancer, such as possible port site metastasis, peritoneal tumor dissemination, inadequate staging, and a questionable quality of cytoreduction [10]. Particularly in the case of AOC, the magnitude of cancer spread in the peritoneum and visceral organs has discouraged and intimidated surgeons from performing endoscopic debulking surgery. Therefore, in contrast to other gynecologic malignancies, the use of laparoscopy in this pathology has frequently been viewed with skepticism and considered the ultimate boundary for the method. The recent introduction into clinical practice of NACT for AOC, coupled with the development of modern technology and an increased number of skilled laparoscopic surgeons, has created a more favorable scenario for endoscopic debulking, at least in selected cases. However, there currently is a notorious paucity of data regarding the feasibility and oncologic safety of this new strategy. In order to show that certain patients affected by AOC would be eligible for and would benefit from a minimal invasive 2
Oncology DOI: 10.1159/000381462
approach, the authors have developed a pilot observational study to evaluate the use of laparoscopic debulking surgery after NACT. The primary objectives of the study were to evaluate the feasibility and operative outcomes of the proposed approach. The secondary objective was to assess the oncologic safety of the method.
Patients and Methods After ethics review board approval (protocol No. 562.944), from January 2011 until March 2014, we conducted a prospective pilot study on patients affected by initially unresectable high-grade serous ovarian cancer (FIGO stage IIIc–IVa) treated with NACT followed by debulking surgery performed by laparoscopy at the Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, Brazil. The inclusion criteria were: (a) histologically confirmed high-grade serous ovarian carcinoma; (b) age >18 and
Oncology DOI: 10.1159/000381462
Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy Giovanni Favero a, e Nathalia Macerox d Tatiana Pfiffer a, e Christhardt Köhler e Vanessa da Costa Miranda b Maria Del Pilar Estevez Diz b Julia Tizue Fukushima c Edmund Chada Baracat a Jesus Paula Carvalho a
Departments of a Gynecology and b Medical Oncology, and c Division of Medical Statistics, Instituto do Câncer do Estado de São Paulo – ICESP, Faculdade de Medicina da Universidade de São Paulo, and d Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; e Department of Advanced Gynecologic Surgery and Oncology, Asklepios Hospital Hamburg, Hamburg, Germany
Abstract Background: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. Objectives: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. Methods: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA125 normalization, imaging without disease in critical areas, and optimal cytoreduction. Results: From January 2011 to
© 2015 S. Karger AG, Basel 0030–2414/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/ocl
March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapyfree interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). Conclusion: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results. © 2015 S. Karger AG, Basel
Dr. Giovanni Favero, Department of Gynecology Instituto do Câncer do Estado de São Paulo – ICESP Faculdade de Medicina da Universidade de São Paulo Av. Dr. Enéas Carvalho de Aguiar 255, 10th Floor, 05403-000 São Paulo, SP (Brazil) E-Mail gdifavero @ hotmail.com
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 4:45:13 PM
Key Words Advanced ovarian cancer · Neoadjuvant chemotherapy · Laparoscopic cytoreduction
In developed countries, ovarian cancer is the second most frequent cancer of the female genital tract and is certainly the most lethal [1]. The incidence and the mortality related to this neoplasm in underprivileged regions have significantly increased over the last decades, and it will certainly constitute a major health care problem in the near future [2]. It is estimated that 125,000 women worldwide die each year due to this condition [3]. Despite a number of screening efforts, approximately 75% of patients are diagnosed with advanced forms of the disease (advanced ovarian cancer, AOC) [4]. Surgery represents the cornerstone of treatment for this condition, and diverse studies have clearly demonstrated that achievement of complete cytoreduction (no macroscopic residual tumor) has a substantial impact on survival [5, 6]. Unfortunately, due to the magnitude of disease dissemination, only in about 20–50% of the patients with AOC is primary optimal debulking surgery technically possible [4, 6, 7]. In this scenario, alternative strategies such as neoadjuvant chemotherapy (NACT), leading to higher rates of adequate resection, may be beneficial to a number of patients who are initially considered inoperable [4, 8]. Operative treatment for gynecologic tumors has historically been performed via laparotomy. Over the last decades, minimally invasive surgery has progressively gained popularity in this particular field. Indeed, laparoscopy significantly reduces procedure-related morbidity [9]. On the other hand, several important oncologic concerns have limited the widespread use of laparoscopy especially in ovarian cancer, such as possible port site metastasis, peritoneal tumor dissemination, inadequate staging, and a questionable quality of cytoreduction [10]. Particularly in the case of AOC, the magnitude of cancer spread in the peritoneum and visceral organs has discouraged and intimidated surgeons from performing endoscopic debulking surgery. Therefore, in contrast to other gynecologic malignancies, the use of laparoscopy in this pathology has frequently been viewed with skepticism and considered the ultimate boundary for the method. The recent introduction into clinical practice of NACT for AOC, coupled with the development of modern technology and an increased number of skilled laparoscopic surgeons, has created a more favorable scenario for endoscopic debulking, at least in selected cases. However, there currently is a notorious paucity of data regarding the feasibility and oncologic safety of this new strategy. In order to show that certain patients affected by AOC would be eligible for and would benefit from a minimal invasive 2
Oncology DOI: 10.1159/000381462
approach, the authors have developed a pilot observational study to evaluate the use of laparoscopic debulking surgery after NACT. The primary objectives of the study were to evaluate the feasibility and operative outcomes of the proposed approach. The secondary objective was to assess the oncologic safety of the method.
Patients and Methods After ethics review board approval (protocol No. 562.944), from January 2011 until March 2014, we conducted a prospective pilot study on patients affected by initially unresectable high-grade serous ovarian cancer (FIGO stage IIIc–IVa) treated with NACT followed by debulking surgery performed by laparoscopy at the Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, Brazil. The inclusion criteria were: (a) histologically confirmed high-grade serous ovarian carcinoma; (b) age >18 and
