publication date: May. 4, 2018

New data prompts CDC to examine adequacy of pre-op workup by gynecologists

By Matthew Bin Han Ong

Robert Redfield

Robert Redfield

Director, Centers for Disease Control and Prevention

 

In response to a congressional letter and a new study on the prevalence of undiagnosed hidden uterine cancers, officials at the Centers for Disease Control and Prevention are considering launching a review of whether gynecologists are sufficiently thorough in evaluating patients in the preoperative setting, according to insiders with knowledge of the agency’s plans.

CDC has the authority to set screening guidelines—for instance, by recommending that gynecologists perform biopsies on women undergoing removal of fibroids to preserve fertility—and may do so if it determines that gynecologists aren’t evaluating patients as rigorously as oncologists in a setting where there is a high risk of encountering unsuspected malignancies.

CDC’s new director, Robert Redfield, appears to be interested in convening an advisory panel of surgical specialists to discuss potential CDC action on this matter, said Larry Kaiser, president and CEO of the Temple University Health System, the Lewis Katz Dean at the School of Medicine, and a professor of thoracic medicine and surgery.

“When I spoke to Dr. Redfield, he’s interested in looking into the situation. He indicated that he would potentially like to put together a panel, but there have been no invites. It was basically a brief discussion to gauge my interest in looking further into this,” Kaiser said to The Cancer Letter.

“I’m pleased to know that the CDC is interested in this issue,” Kaiser said. “Basic surgical principles need to be followed, so that includes things like not disrupting specimens that may be harboring malignancy. I think many in the gynecology community have jumped on board and are not performing morcellation, which is a procedure that really defies anything that we as surgeons would do. Whatever Dr. Redfield ultimately decides to do, I told him that I would certainly be interested in participating.”

Gynecologists may not be performing adequate biopsies to determine whether women undergoing uterine resection—especially patients with fibroids—are at risk of having unsuspected malignancies, Rep. Brian Fitzpatrick (R-PA) wrote in a letter April 24 to CDC’s Redfield.

“I respectfully request that the CDC consider whether the gynecological field should place a more stringent effort on using tissue biopsy to identify the American women who are at risk of having occult cancers of the uterus—in order to protect them from any procedure that might lead to cancer spread or upstaging,” Fitzpatrick wrote.

CDC sources confirmed to The Cancer Letter that a response to Fitzpatrick’s letter has left Redfield’s desk, and is in the process of being cleared by HHS leadership.

This development comes on the heels of an authoritative study, titled “Occult Gynecologic Cancer in Women Undergoing Hysterectomy or Myomectomy for Benign Indications,” published in the journal of Obstetrics and Gynecology by researchers from the Yale School of Medicine.

The team reviewed data from 26,444 women to determine prevalence of unsuspected malignancies and found that nearly 2 percent of women undergoing total laparoscopic or laparoscopic-assisted vaginal hysterectomy have preoperatively undetected malignancy of the corpus uteri.

The study, borne out of the debate about power morcellation, is the first to establish the prevalence of all uterine malignancies that are undiagnosed in the preoperative setting.

“Our study highlights that the risk for occult uterine cancer in presumed benign hysterectomy is higher in women at more advanced age and varies among women undergoing different surgical routes,” said Vrunda Desai, the lead author and an assistant professor of obstetrics, gynecology and reproductive sciences at Yale University School of Medicine. “Further advancements in preoperative screening techniques and shared decision making with patients are vital to providing high quality care.

“In addition, as with all research endeavors, there are methodological challenges and limitations in our study,” Desai said to The Cancer Letter. “Additional research is warranted to help us fully understand the risks and benefits and patterns of care.”

The study, which relies on analysis of data from the 2014-2015 American College of Surgeons National Surgical Quality Improvement Program, also shows that a high number of women—9.72 percent—undergoing total abdominal hysterectomy who are 55 years or older had undiagnosed occult corpus uteri cancer, compared to 1.06 percent of women aged 40 to 54 years.

“Current evidence on the risk of occult uterine malignancy remains highly variable (with estimated prevalence ranging from 0% to 3.17% across studies) and is limited in scope (e.g. surgical approach and patient samples included,” the authors wrote. “To address these gaps in prior research, we aimed to estimate the prevalence of preoperatively undiagnosed corpus uteri, and ovarian malignancy in women undergoing hysterectomy or myomectomy for benign indications.”

Over the past four years, the debate about uterine cancer was largely focused on uterine sarcoma, and especially leiomyosarcoma, because of the controversy surrounding power morcellation stemming from two high-profile cases, Amy Reed and Erica Kaitz, both of which have resulted in death and legal action against Brigham & Women’s Hospital and Karl Storz, a manufacturer of power morcellators (The Cancer Letter, How Medical Devices Do Harm).

Independent analyses by FDA and academic researchers—including a JAMA study by a Columbia University team—established consensus that about 0.3 percent, or 1 in 350 women undergoing hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma.

The Yale paper addresses a much broader—and arguably, more urgent—question: How many women undergoing hysterectomy or myomectomy for presumed benign indications actually have undetected uterine malignancies? Or rather, how many of these occult cancers are being missed by gynecologists performing surgical procedures?

The results indicate that, for women undergoing non-oncological procedures, such as power morcellation or manual morcellation, the stakes are much higher when taking into consideration the prevalence of more common types of gynecologic cancers—endometrial, cervical, and ovarian carcinomas, which, “if preoperatively undiagnosed, may disseminate to the abdominopelvic cavity as well when morcellated.”

This is a signal that gynecologists need to thoroughly evaluate patients who are undergoing hysterectomy, post-menopausal women in particular, said Robert Mannel, director of the Stephenson Cancer Center at the University of Oklahoma, a group chair of NRG Oncology, and the chair of the Protocol Development Committee for Gynecologic Cancers in the NCI National Clinical Trials Network.

“The takeaway that I got from reading this article is that, in a post-menopausal woman, you better really make sure that you are very thorough in your evaluation and particularly if somebody has abnormal uterine bleeding, you really want to make sure,” Mannel said to The Cancer Letter. “You might need more than just an endometrial biopsy or an ultrasound. That individual may need diagnostic hysteroscopy, something that can be even more sensitive at picking up occult malignancies.

“You want to pay attention to everybody, but who are the ones that you really want to pay attention to? I think what the study’s telling you—older women, women who are obese, you need to really pay attention to.”

If all patients had been subjected to appropriate evaluation, the actual number of people with occult uterine cancer would be a much smaller percentage, said Ronald Alvarez, the Betty and Lonnie S. Burnett Professor of Obstetrics and Gynecology, and chair of the Department of Obstetrics and Gynecology at Vanderbilt University Medical Center.

“The concern here is that people aren’t doing the appropriate preoperative evaluation to rule out cancer. It probably represents a failure in our healthcare system,” Alvarez, who is a past co-chair of the NRG Oncology Gynecologic Cancer Committee, said to The Cancer Letter. “It just points out an opportunity, from a quality improvement standpoint, to make sure that everybody who is going to have a hysterectomy has the appropriate assessment for the risk of cancer preoperatively.”

A CDC review will be helpful, said Stephen Rubin, chief of the Division of Gynecologic Oncology, professor in the Department of Surgical Oncology, and the Paul Grotzinger and Wilbur Raab Chair in Surgical Oncology at Fox Chase Cancer Center.

“I think it ought to be looked at, for sure. You ought to be sure a fibroid is benign before you morcellate—it seems to make sense, but the devil is in the details,” Rubin said to The Cancer Letter. “Upstaging [of a uterine cancer] would only be done by morcellation. You know, manual or power. I don’t like morcellation. Even if you could look onto your crystal ball and say these fibroids are benign absolutely, I wouldn’t do power morcellation.”

Rubin said greater reliance on biopsies may not be the perfect solution, especially when evaluating for surgeries that do not follow oncologic surgical principles.

“I think there’d be some risk of underdiagnosis,” Rubin said. “You could stick a needle in a sarcoma and maybe miss the sarcoma part of it and underdiagnose it. Depending on the accuracy of it, you could make things worse. Gynecologists could say ‘I biopsied this mass and they said it was a benign fibroid, so, I’m going to feel free to morcellate it.’

“I think the better idea is don’t morcellate,” Rubin said. “That would solve the problem. Remove it all.”

While en bloc removal of uterine tissue seems to be the safest oncological approach, younger women who elect to retain their uteri for family planning purposes face a conundrum. Myomectomies are, by definition, non-oncological operations with the potential to upstage a hidden cancer.

Therefore, it seems necessary for gynecologists to rule out an occult malignancy in the preoperative setting, and the vast majority of surgeons in other specialties rely on biopsies to evaluate tissues and tumors with malignant potential.

Insiders say CDC’s multidisciplinary panel is expected to focus on this issue— using tissue biopsy to risk-stratify women with symptomatic uterine fibroids for cancer.

“Hopefully, if the CDC convenes this panel, they will be able to address all these concerns and come up with some reasonable recommendations,” Rubin said.

Amy Reed was one of the patients who stood to benefit from a more thorough workup, said Reed’s husband Hooman Noorchashm, a cardiac surgeon who launched an aggressive campaign against morcellation.

“As a surgeon, I am certain that had my wife’s gynecologist biopsied her fibroid tumor, even intraoperatively—she would not have died from abdominal sarcomatosis, as she did,” Noorchashm said.

 

The text of Fitzpatrick’s letter to CDC’s Redfield follows:

Honorable Director Redfield,

I wanted to extend my congratulations on your recent appointment as director of the Centers for Disease Control. I am writing this letter in follow-up to a serious women’s health hazard my office has been critically involved with on behalf of a constituent family in my district for several years now—and to request your careful attention to this potentially serious women’s
health hazard.

As you likely know, in 2014, the U.S. Food and Drug Administration sharply curtailed the use of a medical device known as a Laparoscopic Power Morcellator. This unprecedented action resulted because of concerns regarding the device’s capacity to disseminate, spread and upstage deadly cancers of the uterus in women.

Dr. Amy Josephine Reed, of Yardley, PA, and her family spearheaded the citizen’s public health campaign that initially brought awareness to the press, the medical profession and regulators on this issue. As their representative, I worked with them to make their voices heard on
Capitol Hill.

As a result of the changes to the practice pattern in gynecology, starting in 2014, independent expert groups assessed the incidence of occult cancers in women—specifically focusing on those who undergo “non-oncological” operations. It is my understanding, that performing “non-oncological” operations (such as morcellation) on women harboring occult cancers can result in a potentially deadly spread or upstaging of that cancer.

Recently, my constituents have made me aware that a publication in the prominent journal of the American College of Obstetricians and Gynecology (i.e., the Green Journal) demonstrated that the incidence of occult uterine cancers can be as high as 2% in women who need their uterus removed by surgeons. I have attached the paper here, for your record. Given the vast number of such operations being performed in the U.S. annually, I wonder if such incidence of cancer is much too high to comfortably accept—and I trust you are able to address my question from a public health perspective.

Moreover, as a medical layman, I was quite concerned to learn from my constituent that the gynecology specialty may not be performing any adequate uterine tumor biopsies in order to make a best attempt at identifying the American women at risk of having occult cancers – such as the one my constituent Dr. Reed succumbed to. It is my understanding that other surgeons use biopsy techniques routinely, to determine if all other tumor types carry a cancer. The question for CDC is whether gynecologists are doing enough to identify at risk women.

Therefore, I respectfully request that the CDC consider whether the gynecological field should place a more stringent effort on using tissue biopsy to identify the American women who are at risk of having occult cancers of the uterus—in order to protect them from any procedure that might lead to cancer spread
or upstaging.

With this letter, I am informing you of my constituents’ concern that American women with occult cancers of the uterus may be avoidably exposed to an undue cancer risk.

Please do not hesitate to contact me or my staff member, Joseph Knowles, and I look forward to working with you on this critical women’s health issue in the near future.

With respect,
Brian Fitzpatrick
Member of Congress

Copyright (c) 2018 The Cancer Letter Inc.