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Surgical staging in early ovarian carcinoma: Garcia-Soto et al
Journal Club
www. AJOG.org
Surgical staging in early ovarian carcinoma: Garcia-Soto et al Linda Van Le, MD; George A. Macones, MD, MSCE, Associate Editor The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Garcia-Soto AE, Boren T, Wingo SN, et al. Is comprehensive surgical staging needed for thorough evaluation of early-stage ovarian carcinoma? Am J Obstet Gynecol 2012;206:242.e1-5. The full discussion appears at www.AJOG.org, pages e1-3.
DISCUSSION QUESTIONS
What were the primary and secondary objectives? What was the study design? What statistical tests were applied and why? What were the key findings? What were the study’s strengths and limitations? What is the clinical impact of this study?
From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC:
Moderator Linda Van Le, MD Professor Discussants Amanda Jackson, MD First-Year Fellow Kevin Schuler, MD Second-Year Fellow Anuj Suri, MD Second-Year Fellow Joshua Kilgore, MD First-Year Fellow Emily Ko, MD Third-Year Fellow Paola Gehrig, MD Associate Professor Wendy Brewster, MD Associate Professor L.V.L. is on the Eisai speakers bureau and the advisory board for Biologics. The other authors report no conflict of interest. 0002-9378/free © 2012 Published by Mosby, Inc. doi: 10.1016/j.ajog.2012.01.019
See related article, page 242
T
he American Cancer Society predicted that nearly 22,000 new cases of ovarian cancer would occur in the United States during 2011. In comparison, it was expected that 232,620 cases of breast cancer, 221,130 cases of lung cancer, and 101,340 cases of colon cancer would be diagnosed. Thus, ovarian cancer constitutes a minority of the malignancies occurring in our country. Most cases are advanced upon discovery and require extensive surgery followed by chemotherapy; the outcome is often fatal. However, in approximately 25% of cases, we are lucky enough to diagnose ovarian cancer in an early stage when the prognosis is much better. At that point, it is the surgeon’s task to determine the extent of microscopic disease so that appropriate adjuvant treatment can be recommended. Surgical staging for ovarian cancers has not changed over many years. When the International Federation of Gynecology and Obstetrics (FIGO) last revised its recommendations for the staging of gynecologic cancers in 2009, it did not alter the procedure for staging of ovarian cancer. Aside from removal of the ovaries, staging typically includes hysterectomy, peritoneal biopsies, pelvic washings, diaphragm assessment, and pelvic and periaortic lymphadenectomy. While this may sound like a straightforward algorithm, there are ambiguous areas; explicit guidance on the extent of node dissection, particularly the degree to which periaortic node dissection should be performed; the ideal number of nodes that should be obtained; and random biopsies is lacking. In addition, the suspicious adhesion has yet to be clearly described. Thus, surgeons have much room for individual interpretation.
Also, as we lean towards minimallyinvasive surgery, our goal is to expedite procedures while limiting risk, so that patients can be sent home quickly. If additional time is devoted to staging in the operating room, the surgery should be of high yield. This month, Journal Club members discussed a new study by Garcia-Soto and colleagues. The researchers evaluated the current comprehensive surgical-staging algorithm. Specifically, they query whether patients continue to benefit from performing biopsies of the peritoneum, adhesions, and omentum when disease is seemingly limited to the ovary.
Are peritoneal biopsies important? Garcia-Soto and associates carried out a retrospective review of patients who presented to their institution over a 16-year period. These women had ovarian cancer that was believed to be grossly confined to the ovary. All underwent comprehensive surgical staging by gynecologic oncologists; the procedures were performed in accordance with the Gynecologic Oncology Group staging manual. The researchers report how many patients’ cancers were upstaged due to diagnosis of metastatic disease contained in peritoneal, adhesion, and omental biopsies. They also provide information regarding metastatic disease to lymph nodes and other organs. Their ultimate goal was to determine the significance of routine omentectomy and peritoneal biopsies as part of a comprehensive staging procedure. Of the 86 patients who met the study criteria, 29% (25/86) were given upstaged diagnoses after surgical staging, and 60% (15/25) of these were upstaged due to positive biopsies of the peritoneum, adhesions, or omentum. This
MARCH 2012 American Journal of Obstetrics & Gynecology
263
Journal Club subset represented 17% (15/86) of all study participants. Twenty percent (5/ 25) of patients with upstaged disease—or 6% (5/86) of all participants— had upstaged diagnoses due to disease found in biopsies of the peritoneum and adhesions. When correlated with other clinical factors, grade 3 disease and the presence of ascites were also correlated with a diagnosis of occult metastatic disease; the presence of positive cytology was not.
Sampling tissue that appears normal While 17% of the participants’ disease was upstaged due to results from biopsies of the peritoneum, adhesions, and omentum, it is unknown whether the adhesions actually looked suspicious. In 2011, a similar study of 122 patients found that disease was upstaged in 16% (19/122) of patients due to findings from biopsies of the peritoneum and adhesions; an additional 5 patients’ disease
264
www.AJOG.org was upstaged when microscopic disease was detected in the omentum. The incidence of positive disease is fairly similar between these 2 studies. However, Shroff and colleagues determined that 11% (13/ 122) of positive peritoneal biopsies were found in evidently abnormal tissue, whereas discovery of disease in normallooking peritoneal tissue was less common (5% or 6/122). As one might expect, the yield from biopsies of suspicious areas was higher, but the authors of both studies concluded that it is still worthwhile to biopsy normal-appearing areas. In discussing the Garcia-Soto study, Journal Club members thought that it would have been educational to know specifically how biopsies were obtained and whether these samples were from areas that looked suspicious or were apparently normal. It would have been informative to understand what surgical findings led to biopsies that were positive for disease. Another concern was that
American Journal of Obstetrics & Gynecology MARCH 2012
there had been no gynecologic pathology review. Study patients were treated over a long period of time and most likely, there were different pathologists reviewing specimens. Entities such as endosalpingiosis can be confused with metastatic disease and a gynecologic pathology review to insure uniformity of diagnoses would have been reassuring.
No changes for now In summary, we will probably not change our surgical staging procedure in the near future. The work by Garcia-Soto and colleagues showed that positive biopsies led to upstaging. Their findings support the practice of sampling the peritoneum, adhesions, and omentum in women who have cancers that appear to be confined to the ovaries. Biopsies are easy to perform and pose little risk to the patient. Until ample data indicate otherwise, comprehensive surgical staging should continue in this population. f
www. AJOG.org
Surgical staging in early ovarian carcinoma: Garcia-Soto et al Linda Van Le, MD; George A. Macones, MD, MSCE, Associate Editor The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Garcia-Soto AE, Boren T, Wingo SN, et al. Is comprehensive surgical staging needed for thorough evaluation of early-stage ovarian carcinoma? Am J Obstet Gynecol 2012;206:242.e1-5. The full discussion appears at www.AJOG.org, pages e1-3.
DISCUSSION QUESTIONS
What were the primary and secondary objectives? What was the study design? What statistical tests were applied and why? What were the key findings? What were the study’s strengths and limitations? What is the clinical impact of this study?
From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC:
Moderator Linda Van Le, MD Professor Discussants Amanda Jackson, MD First-Year Fellow Kevin Schuler, MD Second-Year Fellow Anuj Suri, MD Second-Year Fellow Joshua Kilgore, MD First-Year Fellow Emily Ko, MD Third-Year Fellow Paola Gehrig, MD Associate Professor Wendy Brewster, MD Associate Professor L.V.L. is on the Eisai speakers bureau and the advisory board for Biologics. The other authors report no conflict of interest. 0002-9378/free © 2012 Published by Mosby, Inc. doi: 10.1016/j.ajog.2012.01.019
See related article, page 242
T
he American Cancer Society predicted that nearly 22,000 new cases of ovarian cancer would occur in the United States during 2011. In comparison, it was expected that 232,620 cases of breast cancer, 221,130 cases of lung cancer, and 101,340 cases of colon cancer would be diagnosed. Thus, ovarian cancer constitutes a minority of the malignancies occurring in our country. Most cases are advanced upon discovery and require extensive surgery followed by chemotherapy; the outcome is often fatal. However, in approximately 25% of cases, we are lucky enough to diagnose ovarian cancer in an early stage when the prognosis is much better. At that point, it is the surgeon’s task to determine the extent of microscopic disease so that appropriate adjuvant treatment can be recommended. Surgical staging for ovarian cancers has not changed over many years. When the International Federation of Gynecology and Obstetrics (FIGO) last revised its recommendations for the staging of gynecologic cancers in 2009, it did not alter the procedure for staging of ovarian cancer. Aside from removal of the ovaries, staging typically includes hysterectomy, peritoneal biopsies, pelvic washings, diaphragm assessment, and pelvic and periaortic lymphadenectomy. While this may sound like a straightforward algorithm, there are ambiguous areas; explicit guidance on the extent of node dissection, particularly the degree to which periaortic node dissection should be performed; the ideal number of nodes that should be obtained; and random biopsies is lacking. In addition, the suspicious adhesion has yet to be clearly described. Thus, surgeons have much room for individual interpretation.
Also, as we lean towards minimallyinvasive surgery, our goal is to expedite procedures while limiting risk, so that patients can be sent home quickly. If additional time is devoted to staging in the operating room, the surgery should be of high yield. This month, Journal Club members discussed a new study by Garcia-Soto and colleagues. The researchers evaluated the current comprehensive surgical-staging algorithm. Specifically, they query whether patients continue to benefit from performing biopsies of the peritoneum, adhesions, and omentum when disease is seemingly limited to the ovary.
Are peritoneal biopsies important? Garcia-Soto and associates carried out a retrospective review of patients who presented to their institution over a 16-year period. These women had ovarian cancer that was believed to be grossly confined to the ovary. All underwent comprehensive surgical staging by gynecologic oncologists; the procedures were performed in accordance with the Gynecologic Oncology Group staging manual. The researchers report how many patients’ cancers were upstaged due to diagnosis of metastatic disease contained in peritoneal, adhesion, and omental biopsies. They also provide information regarding metastatic disease to lymph nodes and other organs. Their ultimate goal was to determine the significance of routine omentectomy and peritoneal biopsies as part of a comprehensive staging procedure. Of the 86 patients who met the study criteria, 29% (25/86) were given upstaged diagnoses after surgical staging, and 60% (15/25) of these were upstaged due to positive biopsies of the peritoneum, adhesions, or omentum. This
MARCH 2012 American Journal of Obstetrics & Gynecology
263
Journal Club subset represented 17% (15/86) of all study participants. Twenty percent (5/ 25) of patients with upstaged disease—or 6% (5/86) of all participants— had upstaged diagnoses due to disease found in biopsies of the peritoneum and adhesions. When correlated with other clinical factors, grade 3 disease and the presence of ascites were also correlated with a diagnosis of occult metastatic disease; the presence of positive cytology was not.
Sampling tissue that appears normal While 17% of the participants’ disease was upstaged due to results from biopsies of the peritoneum, adhesions, and omentum, it is unknown whether the adhesions actually looked suspicious. In 2011, a similar study of 122 patients found that disease was upstaged in 16% (19/122) of patients due to findings from biopsies of the peritoneum and adhesions; an additional 5 patients’ disease
264
www.AJOG.org was upstaged when microscopic disease was detected in the omentum. The incidence of positive disease is fairly similar between these 2 studies. However, Shroff and colleagues determined that 11% (13/ 122) of positive peritoneal biopsies were found in evidently abnormal tissue, whereas discovery of disease in normallooking peritoneal tissue was less common (5% or 6/122). As one might expect, the yield from biopsies of suspicious areas was higher, but the authors of both studies concluded that it is still worthwhile to biopsy normal-appearing areas. In discussing the Garcia-Soto study, Journal Club members thought that it would have been educational to know specifically how biopsies were obtained and whether these samples were from areas that looked suspicious or were apparently normal. It would have been informative to understand what surgical findings led to biopsies that were positive for disease. Another concern was that
American Journal of Obstetrics & Gynecology MARCH 2012
there had been no gynecologic pathology review. Study patients were treated over a long period of time and most likely, there were different pathologists reviewing specimens. Entities such as endosalpingiosis can be confused with metastatic disease and a gynecologic pathology review to insure uniformity of diagnoses would have been reassuring.
No changes for now In summary, we will probably not change our surgical staging procedure in the near future. The work by Garcia-Soto and colleagues showed that positive biopsies led to upstaging. Their findings support the practice of sampling the peritoneum, adhesions, and omentum in women who have cancers that appear to be confined to the ovaries. Biopsies are easy to perform and pose little risk to the patient. Until ample data indicate otherwise, comprehensive surgical staging should continue in this population. f