Tag Archives: CA-125 surveillance

U.K. NICE Issues New Clinical Guidelines Re Recognition & Initial Management of Ovarian Cancer

Posted on by

On April 27, 2011, the U.K. National Institute For Health and Clinical Excellence issued new clinical guidelines regarding the recognition and initial management of ovarian cancer.

On April 27, 2011, the U.K. National Institute For Health and Clinical Excellence (NICE) issued new clinical guidelines regarding the recognition and initial management of ovarian cancer.

In the first ever clinical guideline for ovarian cancer, NICE is calling for more initial investigations to take place in primary care settings, such as general practice (GP) surgeries, so that women can be referred to hospital specialists sooner and begin treatment. This guidance updates and replaces recommendation 1.7.4 in Referral guidelines for suspected cancer (NICE clinical guideline 27; published 2005).

NICE also produced a series of tools to help U.K. healthcare professionals put this new guidance into practice, including guidance documents for doctors and patients, podcasts, clinical case scenarios and a slide set. To view a complete list of all NICE-produced guidance materials available to doctors and patients, visit http://guidance.nice.org.uk/CG122.

The full text NICE ovarian cancer clinical guidelines are classified under the following six chapter headings:

  • Epidemiology
  • Detection in Primary Care
  • Establishing the Diagnosis in Primary Care
  • Management of Suspected Early (stage I) Ovarian Cancer
  • Management of Advanced (stage II-IV) Ovarian Cancer
  • Support Needs of Women With Newly Diagnosed Ovarian Cancer

The key priorities identified by NICE for successful implementation of the new ovarian cancer clinical guidelines by primary and secondary healthcare professionals include the topics addressed below.

Awareness of Symptoms & Signs

— Carry out tests in primary care if a woman (especially if 50 or over) reports having any of the following symptoms on a persistent or frequent basis – particularly more than 12 times per month:

  • persistent abdominal distension (women often refer to this as “bloating”);
  • feeling full (early satiety) and/or loss of appetite;
  • pelvic or abdominal pain; and/or
  • increased urinary urgency and/or frequency.

— Carry out appropriate tests for ovarian cancer in any woman of 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS), because IBS rarely presents for the first time in women of this age.

Asking the Right Question – First Tests

— Measure serum CA125 in primary care in women with symptoms that suggest ovarian cancer.

— If serum CA125 is 35 IU/ml or greater, arrange an ultrasound scan of the abdomen and pelvis.

— For any woman who has normal serum CA125 (less than 35 IU/ml), or CA125 of 35 IU/ml or greater but a normal ultrasound:

  • assess her carefully for other clinical causes of her symptoms and investigate if appropriate; and
  • if no other clinical cause is apparent, advise her to return to her general practitioner (GP) if her symptoms become more frequent and/or persistent.

Malignancy Indices

— Calculate a risk of malignancy index I (RMI I) score (after performing an ultrasound) and refer all women with an RMI I score of 250 or greater to a specialist multidisciplinary team.

— Risk of malignancy index I (RMI I): RMI I is a product of the ultrasound scan score (U), menopausal status (M) and serum CA125 level.

— RMI I = U x M x  CA125

  • The ultrasound result is scored 1 point for each of the following characteristics: multilocular cysts, solid areas, metastases, ascites, and bilateral lesions. U = 0 for an ultrasound score of 0 points, U = 1 for an ultrasound score of 1 point, U = 3 for an ultrasound score of 2–5 points.
  • Menopausal status is scored as 1 = pre-menopausal and 3 = post-menopausal. The classification of “post-menopausal” is a woman who has had no period for more than 1 year or a woman over 50 who has had a hysterectomy.
  • Serum CA125 is measured in IU/ml.

Tissue Diagnosis

— If offering cytotoxic chemotherapy to women with suspected advanced ovarian cancer, first obtain a confirmed tissue diagnosis by histology (or by cytology if histology is not appropriate) in all but exceptional cases.

The Role of Systematic Retroperitoneal Lymphadenectomy

— Do not include systematic retroperitoneal lymphadenectomy (block dissection of lymph nodes from the pelvic side walls to the level of the renal veins) as part of standard surgical treatment in women with suspected ovarian cancer whose disease appears to be confined to the ovaries (that is, who appear to have stage I disease).

Adjuvant Systemic Chemotherapy For Stage I Disease

— Do not offer adjuvant chemotherapy to women who have had optimal surgical staging and have low-risk stage I disease ([tumor] grade 1 or 2, stage Ia or Ib).

Support Needs of Women with Newly Diagnosed Ovarian Cancer

— Offer all women with newly diagnosed ovarian cancer information about their disease, including psychosocial and psychosexual issues, that:

  • is available at the time they want it;
  • includes the amount of detail that they want and are able to deal with; and
  • is in a suitable format, including written information.

Source:  Ovarian cancer: the recognition and initial management of ovarian cancer (CG122), Full Guideline, National Institute For Health & Clinical Excellence (NICE), U.K. National Health Service (NHS), April 2011.

Additional Information:

2011 NCCN Conference: New Treatment Options Lead to Steady Progress Against Ovarian Cancer

Posted on by

Recommendations stemming from recent clinical trials highlight notable updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Ovarian Cancer at the National Comprehensive Cancer Network® (NCCN®) 16th Annual Conference.

Robert J. Morgan, Jr., M.D., Professor of Medical Oncology, City of Hope Comprehensive Cancer Center; Chair, NCCN Guidelines Panel for Ovarian Cancer

Although finding effective screening tools remains a priority, new treatment options for women with ovarian cancer, such as the ones outlined in the updated NCCN Guidelines for Ovarian Cancer,[1] are vital to making steady progress against the disease according to Robert J. Morgan, Jr., M.D., of City of Hope Comprehensive Cancer Center and chair of the NCCN Guidelines Panel for Ovarian Cancer. Dr. Morgan outlined significant updates to the NCCN Guidelines during a recent presentation at the NCCN 16th Annual Conference.

The NCCN Guidelines address epithelial ovarian cancer (including borderline or low malignant potential) and less common histopathologies, including malignant germ neoplasms, carcinosarcomas, and sex cord-stromal tumors. They also discuss fallopian tube cancer and primary peritoneal cancer, which are less common neoplasms that are managed in a similar manner to epithelial ovarian cancer.

“Regardless of the type of cancer, the NCCN Guidelines for Ovarian Cancer reflect the importance of stage and grade of disease on prognosis and treatment recommendations,” said Dr. Morgan.

The NCCN Guidelines continue to recommend that women with borderline epithelial ovarian cancer of low malignant potential be primarily surgically managed. In contrast to patients with frankly invasive ovarian carcinoma, women with borderline disease tend to be younger and are often diagnosed with stage I disease.

“The benefits of postoperative chemotherapy has not been demonstrated for patients who have no microscopically demonstrable invasive implants, said Dr. Morgan. “Even patients with advanced stage disease at presentation have an excellent prognosis and chemotherapy should be avoided.”

The NCCN Guidelines recommend surgery limited to a unilateral salpingo-oophorectomy (USO) (preserving the uterus and contralateral ovary) for women who wish to maintain their fertility, and standard ovarian cancer debulking surgery is recommended for those not concerned about fertility preservation.

On the contrary, in women diagnosed with stage II, III, or IV epithelial ovarian cancer, the NCCN Guidelines recommend intraperitoneal chemotherapy for first-line therapy and have been updated to include dose-dense paclitaxel (Taxol®:, Bristol-Myers Squibb) as a possible treatment option.

Dr. Morgan noted that in a recent clinical trial, dose-dense weekly paclitaxel with carboplatin (Paraplatin®:, Bristol-Myers Squibb) showed an increase in both progression-free survival and overall survival when compared with conventional intraperitoneal chemotherapy of weekly carboplatin/paclitaxel.[2]

“However, the dose-dense regimen is more toxic, and patients discontinued dose-dense paclitaxel therapy more often than those receiving standard therapy,” stated Dr. Morgan. “As with all treatment decisions, the patient needs to weigh the potential benefits and risks and discuss them thoroughly with their physician.”

Dr. Morgan discussed two additional phase 3 trials assessing bevacizumab (Avastin®:, Genentech/Roche) combined with carboplatin/paclitaxel in the upfront setting compared to carboplatin/paclitaxel alone.[3-4] Although data regarding overall survival and quality of life have not been reported yet, the studies did indicate that the median progression-free survival increased in patients receiving bevacizumab as a first line and maintenance therapy.

“Only modest improvements in progression-free survival were observed in both of these trials. The NCCN Guidelines Panel prefers to await mature results of these trials prior to recommending the routine addition of bevacizumab to carboplatin/paclitaxel,” said Dr. Morgan.

As such, the updated NCCN Guidelines includes new language detailing the Panel’s view on bevacizumab encouraging participation in ongoing clinical trials that are further investigating the role of anti-angiogenesis agents in the treatment of ovarian cancer, both in the upfront and recurrence settings.

Biomarkers continue to emerge as an area of interest in predicting future patterns of the disease. In patients with ovarian cancer, Dr. Morgan discussed the value of monitoring CA-125 levels in regards to a recent study[5] comparing early versus delayed treatment of relapsed ovarian cancer.

“Often, levels of CA-125 have been shown to rise prior to a clinical or symptomatic relapse in women with ovarian cancer. This trial looked at whether there was a benefit of early treatment on the basis of increased CA-125 concentrations compared with delayed treatment on the basis of clinical recurrence,” said Dr. Morgan.

The study, which was published in The Lancet, found that there was no survival benefit to early institution of treatment based on increased CA-125 levels and that the quality of life was superior in patients in the late treatment arm.

“The results of the trial suggest that the utility of the routine monitoring of CA-125 levels in limited,” said Dr. Morgan. “The NCCN Guidelines Panel encourages patients and their physicians to actively discuss the pros and cons of CA-125 monitoring based upon these findings and have updated the NCCN Guidelines to include language supporting this recommendation.”

Virtually all drugs used in oncology have the potential to cause adverse drug reactions while being infused, which can be classified as either infusion or allergic reactions. Recently, hypersensitivity to platinum compounds has been recognized as a potential issue for patients being administered these compounds.

“Platinum compounds remain very important in the treatment of ovarian cancer in both the upfront and recurrence settings, so it was important to design strategies to allow for the safe desensitization of these agents in patients who develop allergies,” said Dr. Morgan.

Standard desensitization regimens include slowly increasing infusion concentrations over several hours. However, Dr. Morgan noted that these procedures must be done in a specific manner in order to be safely administered and pointed to the recommendations within the updated NCCN Guidelines discussing the management of drug reactions.

In conclusion, Dr. Morgan emphasized that although steady progress is being made in the treatment of ovarian cancer, further trials are necessary to investigate the role of targeted agents alone and in combination in newly diagnosed and recurrent ovarian cancer. In addition, enrollment of patients with ovarian cancer must be encouraged.

The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions. The most recent version of this and all NCCN Guidelines are available free of charge at NCCN.org. The NCCN Guidelines for Patients™: Ovarian Cancer is available at NCCN.com.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. For more information, visit NCCN.org.

The NCCN Member Institutions are:

  • City of Hope Comprehensive Cancer Center
  • Dana-Farber/Brigham and Women’s Cancer Center
  • Massachusetts General Hospital Cancer Center
  • Duke Cancer Institute
  • Fox Chase Cancer Center
  • Huntsman Cancer Institute at the University of Utah
  • Fred Hutchinson Cancer Research Center / Seattle Cancer Care Alliance
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Memorial Sloan-Kettering Cancer Center
  • H. Lee Moffitt Cancer Center & Research Institute
  • The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute
  • Roswell Park Cancer Institute
  • Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
  • St. Jude Children’s Research Hospital / University of Tennessee Cancer Institute
  • Stanford Comprehensive Cancer Center
  • University of Alabama at Birmingham Comprehensive Cancer Center
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • University of Michigan Comprehensive Cancer Center
  • UNMC Eppley Cancer Center at The Nebraska Medical Center
  • The University of Texas MD Anderson Cancer Center
  • Vanderbilt-Ingram Cancer Center

References:

1/ Ovarian Cancer Including Fallopian Tube Cancer & Primary Peritoneal Cancer, Version 2.2011, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), National Comprehensive Cancer Network. [PDF Adobe Reader Document – requires free registration and log-in at NCCN.org]

2/ Katsumata N, Yasuda M, Takahashi F, et. al. Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18. PubMed PMID: 19767092.

3/ Burger RA, Brady MF, Bookman MA, et. al.  Phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC):  a Gynecologic Oncology Group study.  J Clin Oncol 28:18s, 2010 (suppl; abstr LBA1).

4/ Perren T, Swart AM, Pfisterer J, et. al. ICON7: A phase III randomized gynecologic cancer intergroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC).Ann Oncol 21;viii2, 2010 (suppl 8; abstr LBA4).

5/Rustin G, van der Burg M, Griffin C, et. al. Early versus delayed treatment of relapsed ovarian cancer. Lancet. 2011 Jan 29;377(9763):380-1. PubMed PMID: 21277438.

Source:

Additional 2011 NCCN Annual Meeting Information