NCCN: Continuing Education
Accreditation Statement
This activity has been designated to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center‘s Commission on Accreditation.
This activity is accredited for 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.
National Comprehensive Cancer Network is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCCN designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of continuing education credit in states that recognize ACPE accredited providers. This is a knowledge-based activity. UAN: 0836-0000-13-015-H01-P
All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/30997; and 4) view/print certificate.
Release date: October 25, 2013; Expiration date: October 25, 2014
Learning Objectives:
Upon completion of this activity, participants will be able to:
Integrate into professional practice the updates to NCCN Guidelines for Ovarian Cancer
Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Ovarian Cancer
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
Ovarian Cancer
These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. Four topics were selected based on recent important updates in the NCCN Guidelines and debate among panel members about recent clinical trials. The topics include 1) intraperitoneal (IP) chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. The recently published NCCN Guidelines Insights on Ovarian Cancer discuss other topics, including 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease (mainly epithelial ovarian cancer), and 6) management of drug/hypersensitivity reactions.1
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
In 2013, an estimated 22,200 new diagnoses of and 14,000 deaths from ovarian cancer will occur in the United States.2 The NCCN Guidelines for Ovarian Cancer discuss management of epithelial ovarian cancer, which is the most common type of ovarian cancer (to view the most recent version of these guidelines, visit NCCN.org). The 4 main histologic subtypes of epithelial ovarian cancer are serous, endometrioid, mucinous, and clear cell; however, most patients (≈70%) have serous histology.3-7 Although some histologic subtypes respond differently, recommended primary treatment for these histologic subtypes does not currently differ; all are treated using the recommendations for epithelial ovarian cancer.4
The NCCN Guidelines also discuss less common cancers, such as Fallopian tube cancer and primary peritoneal cancer, which are managed in a similar manner to epithelial ovarian cancer. Less common ovarian histopathologies are also described, including malignant germ cell neoplasms, carcinosarcomas (malignant mixed Müllerian tumors of the ovary [MMMT]), and sex cord-stromal tumors. Another less common ovarian neoplasia is borderline epithelial ovarian tumor, which is less sensitive to chemotherapy than epithelial ovarian cancer and, in general, is managed surgically like malignant ovarian cancer except in specific circumstances.
These NCCN Guidelines Insights also discuss why some recommendations are category 2B and not category 2A or even category 1. For category 2A and 2B recommendations, the level of evidence to support the intervention is the same (eg, phase II randomized trial, phase III trial that has not been published yet). However, category 2A recommendations have greater consensus among panel members. A category 2B recommendation means that most panel members agree the intervention is appropriate; however, some panel members would use other listed interventions (or may use other interventions in a different order), but do not feel that the listed intervention is inappropriate.
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
IP Chemotherapy
Surgical cytoreduction (debulking) is recommended as initial treatment for many women with ovarian cancer, even those with metastatic disease.8-13 After surgical debulking, adjuvant systemic therapy (eg, taxane/platinum) is recommended for many patients (see OV-3, page 1201);14 several different systemic regimens are recommended (see OV-D, page 1203).15 Primary adjuvant therapy regimens include intravenous with (or without) IP options.14,16-19 All of the regimens may be used for epithelial ovarian, primary peritoneal, and Fallopian tube cancers.
IP chemotherapy is recommended (category 1) for selected stage III patients with optimally debulked (<1 cm residual) disease (ie, low-volume residual disease) based on randomized controlled trials (see OV-3, page 1201).16,20-24 Patients with optimally debulked stage II disease may also receive IP chemotherapy, although no randomized evidence has been published; therefore, this is a category 2A recommendation.25-30 However, IP chemotherapy is not recommended for patients with stage I and IV disease in the NCCN Guidelines. In women with stage III cancer who had residual disease measuring less than 1 cm after debulking, survival was increased by 16 months after IP therapy using cisplatin/paclitaxel when compared with standard intravenous therapy (65.6 vs 49.7 months; P=.03).15 Recent long-term follow-up data have confirmed this extraordinary survival advantage.31 Overall survival was 110 months in patients with stage III ovarian cancer and no residual disease was found in those who received the IP regimen.31 Although whether to use IP chemotherapy (vs intravenous chemotherapy alone) may be difficult to decide, the excellent survival rates for IP chemotherapy make this a valid option for selected patients.31-37 Women with primary peritoneal cancer, Fallopian tube cancer, or MMMT can also be considered for IP chemotherapy, although MMMT has not been included in IP chemotherapy trials.21,38 However, MMMT/carcinosarcoma is basically papillary serous carcinoma (ie, a poorly differentiated carcinoma); therefore, IP may be used for MMMT.
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
Potential toxicities associated with the IP paclitaxel/cisplatin regimen include leukopenia, infection, fatigue, renal toxicity, abdominal discomfort, neurotoxicity, and catheter complications.24,32,39-41 Patients with poor performance status, comorbidities, or advanced age may not tolerate the IP regimen. Patients with stage IV disease have generally not been included in randomized trials of IP therapy; thus, its benefits have not been demonstrated in this group. Strategies to decrease toxicity and improve compliance with the IP chemotherapy regimen include using carefully selected patients, modifying dose and/or schedule, decreasing catheter complications, and using expert nursing care (see “Principles of Chemotherapy” and the discussion in the full version of these guidelines, available at NCCN.org).14,32 The recommended IP chemotherapy regimen is paclitaxel, 135 mg/m2 continuous intravenous infusion over 3 or 24 hours on day 1; cisplatin, 75 to 100 mg/m2 IP on day 2 after intravenous paclitaxel; and paclitaxel, 60 mg/m2 IP on day 8; repeated every 3 weeks for 6 cycles (category 1).16 Note that this IP chemotherapy regimen includes intravenous paclitaxel, so that systemic disease can also be treated. The published randomized trial for this IP chemotherapy regimen used intravenous continuous infusion of paclitaxel over 24 hours.16
For the 2013 update of these NCCN Guidelines, the dosing for the IP chemotherapy regimen was revised to include a 3-hour infusion of paclitaxel, because it has been reported to be more convenient, easier to tolerate, and less toxic than a 24-hour infusion (see OV-D, page 1203).42 However, a randomized trial comparing a 3-hour versus a 24-hour infusion of paclitaxel has not been performed to determine whether they are equivalent. Using a lower IP cisplatin dose of 75 mg/m2 (GOG 252) or splitting the dose may also help to decrease toxicity.28,42-44 Previously, capping doses at a maximum body surface area of 2.0 m2 was recommended to reduce toxicity; however, this restriction was deleted in the 2013 update. If obese women receive doses based on their actual body weight, data suggest that they do not experience more toxicity; therefore, dose capping does not seem to be necessary and may result in suboptimal treatment.45-48 Women should receive intravenous therapy if they are unable to complete IP therapy. Currently, the number of cycles of IP chemotherapy necessary to maintain a survival advantage is unclear,28 although recent data suggest that survival correlates with the number of IP cycles received.49 After 5 years, more women who received 5 or 6 cycles of IP chemotherapy were alive (59%) than those who only received 3 or 4 cycles (33%) or even 1 to 2 cycles (18%).50
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
NCCN Guidelines Insights: Ovarian Cancer, Version 2.2013
Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 10; 10.6004/jnccn.2013.0142
CA-125 Monitoring for Ovarian Cancer Recurrence
Patients who have been treated for ovarian cancer and have experienced a complete response are carefully followed (monitored) to determine whether the disease has recurred. Monitoring includes measuring blood CA-125 levels if they were initially increased, physical and pelvic examinations, and other tests if indicated, such as imaging (see OV-5, page 1202).51-55 For asymptomatic patients with only biochemical evidence of relapse (ie, with increased CA-125 levels but without radiographic and/or clinical evidence of relapse), treatment options include delaying treatment until clinical evidence of relapse (category 2A) or providing immediate treatment (category 2B). The NCCN Guidelines recommend (category 2A) that treatment should be delayed until clinical evidence of relapse (eg, ascites, abdominal/pelvic/back pain, weight loss, bloating, obstruction) based on a recent European trial (see OV-5, page 1202).56
A recent multi-institutional European trial assessed the use of CA-125 monitoring for ovarian cancer recurrence after primary therapy.56,57 Data suggest that treating recurrences early (based on detectable CA-125 levels in otherwise asymptomatic patients) is not associated with an increase in survival, and is associated with a decrease in quality of life.58 The NCCN Ovarian Cancer Panel recommends that patients discuss the pros and cons of CA-125 monitoring with their physicians. However, patients often prefer to have CA-125 monitoring.59 Several articles discuss CA-125 monitoring in greater detail.60-63
Surveillance Recommendations for Less Common Ovarian Histopathologies
Malignant germ cell tumors and sex cord-stromal tumors are rare. For the 2013 update, panel members added surveillance recommendations for germ cell neoplasms and sex cord-stromal tumors based on recent recommendations from the Society for Gynecology Oncology (see LCOH-B, page 1205).60 The recommendations are different for the 2 types of tumors, because sex cord-stromal tumors can recur many years after initial diagnosis and treatment.
Therapy for Recurrent Disease
Although most patients with ovarian cancer experience a response to initial treatment, 75% to 80% will experience a relapse of their disease. Patients with ovarian cancer will often receive multiple types of recurrence therapy, because their disease frequently responds to sequential therapies. Recurrence therapy for patients with epithelial ovarian cancer, Fallopian tube cancer, and primary peritoneal cancer was discussed in detail in a recent NCCN Guidelines Insights.1 The recommended options for recurrence therapy are shown in the NCCN Guidelines for Ovarian Cancer, including the preferred agents (available at NCCN.org). For the 2013 update, panel members added a new preferred regimen—carboplatin/gemcitabine/bevacizumab (category 2B)—based on the recent OCEANS trial (see OV-E, page 1204). This phase III randomized trial assessed carboplatin/gemcitabine with and without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer who had not previously received bevacizumab. In patients receiving the chemotherapy/bevacizumab arm, progression-free survival was increased when compared with chemotherapy alone (12.4 vs 8.4 months; P<.0001).64 However, overall survival was not increased in the chemotherapy/bevacizumab arms. Combination therapy with bevacizumab is a category 2B recommendation, because there is less consensus that this intervention would be routinely used by the panel members. Many of the panel members feel that other combination regimens may be more beneficial and effective than those with bevacizumab. In addition, the carboplatin/gemcitabine/bevacizumab regimen is only recommended in patients who have not previously received bevacizumab. Based on 2 phase II trials, panel members feel that bevacizumab alone is potentially active in patients who have recurrent disease (especially those with ascites), which is reflected in the category 2A recommendation for single-agent bevacizumab.65-68
Summary of the Major Updates
Four update topics are discussed in these NCCN Guidelines Insights. The 4 update topics include 1) IP chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent disease (mainly epithelial ovarian cancer).
After initial surgery, IP chemotherapy is recommended (category 1) for selected stage III patients with low-volume residual disease.16,20-24 For the 2013 update, the dosing for the IP chemotherapy regimen was revised to include a 3-hour infusion of paclitaxel, because it has been reported to be more convenient, easier to tolerate, and less toxic (see OV-D, page 1203).42 However, a 3-hour infusion of paclitaxel has not been proven to be equivalent to a 24-hour infusion in a randomized controlled trial. Previously, capping doses at a maximum body surface area of 2.0 m2 was recommended to reduce toxicity; however, for the 2013 update, this restriction was deleted in the NCCN Guidelines. If obese women receive doses based on their actual body weight, data suggest that they do not have increased toxicity; therefore, dose capping does not seem to be necessary and may result in suboptimal treatment.45-48
For the 2013 update, the panel added surveillance recommendations for germ cell neoplasms and sex cords-tromal tumors based on recent recommendations from the Society for Gynecology Oncology (see LCOH-B, page 1205).60
Patients who have been treated for ovarian cancer and have had a complete response are carefully monitored to determine whether the disease has recurred. The NCCN Guidelines recommend (category 2A) that treatment for ovarian cancer should be delayed until radiographic and/or clinical evidence of relapse (eg, ascites, abdominal/pelvic/back pain, weight loss, bloating, and obstruction; see OV-5, page 1202).56 A recent trial suggests that treating recurrences early (based only on detectable CA-125 levels in otherwise asymptomatic patients) is not associated with an increase in survival but is associated with a decrease in quality of life.56-58 Therefore, early immediate treatment is only a category 2B recommendation in the NCCN Guidelines.
For the 2013 update, panel members have added a new preferred recurrence therapy regimen of carboplatin/gemcitabine/bevacizumab (category 2B) based on the recent OCEANS trial (see OV-E, page 1204).64 However, combination therapy with bevacizumab is a category 2B recommendation, because less consensus exists among the panel that this intervention would be routinely used. Many of the panel members feel that other combination regimens are potentially more beneficial and effective than those with bevacizumab. Recurrence therapy for patients with epithelial ovarian cancer, Fallopian tube cancer, and primary peritoneal cancer was discussed in detail in a recent NCCN Guidelines Insights.1 The recommended options for recurrence therapy are shown in the NCCN Guidelines for Ovarian Cancer, including the preferred agents (see OV-E, page 1204).
EDITOR: Kerrin M. Green, MA, Assistant Managing Editor, JNCCN—Journal of the National Comprehensive Cancer Network, has disclosed that she has no relevant financial relationships.
CE AUTHORS: Deborah J. Moonan, RN, BSN, Manager, CE Supporter Outreach, has disclosed the following relationships with commercial interests: AstraZeneca: Stockholder/Former Employee. Kristina M. Gregory, RN, MSN, OCN, Vice President, Clinical Information Operations, has disclosed that she has no relevant financial relationships. Mary A. Dwyer, MS, Guidelines Coordinator, has disclosed no relevant financial relationships. Miranda Hughes, PhD, Oncology Scientist/Senior Medical Writer, has disclosed no relevant financial relationships.
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