August 2005: Who should operate on Ovarian Cancer?

ARTICLE IN PRESS
Review
Who should operate on patients with ovarian cancer?
An evidence-based review

Kurt Christopher Giede*, Katharina Kieser, Jason Dodge, Barry Rosen
University of Toronto, Canada
Received 5 June 2005

Abstract
Objective. To evaluate the relationship between surgical specialty and survival in patients receiving initial surgical management for
ovarian epithelial cancer.

Study methods. An analytic framework was constructed to address the principle question Fdoes the type of surgeon operating on patients
with newly diagnosed ovarian epithelial cancer influence survival?_ A literature search addressing the components of this analytic framework
was carried out using the Cochrane Library, Medline, EMBASE, and HealthSTAR databases. Relevant articles were selected and graded
using U.S. Preventive Services Task Force and Canadian Task Force guidelines. Results were summarized by quality as well as level of
evidence.

Results. Eighteen studies were reviewed. The quality of evidence was good in 3, fair in 8, and poor in 7 of the studies. The most common
study flaws encountered were Ffailure to account for confounders_ and Fincompleteness of data_. In studies focusing on advanced disease,
there was good quality evidence to support a 6- to 9-month median survival benefit for patients operated on by gynecologic oncologists rather
than general gynecologists and/or general surgeons ( P values 0.009 to 0.01). Studies focusing on early stage disease found gynecologic
oncologists more likely to carry out optimal staging ( P values 0.001 to 0.01). Increased survival could be explained by improved
identification of true stage I patients.

Conclusion. Patients receiving initial surgical management for ovarian epithelial cancer should be operated on by gynecologic
oncologists.


Gynecologic Oncology xx (2005) xxx – xxx
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ARTICLE IN PRESS

Introduction

In the past two decades, there has been increasing interest
in the relationship between surgical specialty and outcomes
in cancer treatment [1].
Surgical specialty has been shown to have a positive
influence on outcomes in a variety of cancers [1–6]. In
ovarian cancer, a relationship between sub-specialty training
and survival has been suggested [1].
Although recommendations and guidelines on the
management of ovarian cancer exist [7–13], to date, there
have been no thorough evidence-based reviews specifically
addressing the question Fdoes the type of surgeon operating
on patients with newly diagnosed ovarian epithelial cancer
influence long-term survival?_
The following review was conducted not only to examine
the quantity but also the quality of evidence regarding a
possible relationship between surgical specialty and survival
outcomes in ovarian cancer.

Methods
Our review followed the methodology established by
the 2001 U.S. Preventive Services Task Force (USPSTF)
and Canadian Task Force (CTF) guidelines [14,15]. An
analytic framework was constructed in order to better
understand the influence of surgical specialty on survival
in patients with newly diagnosed ovarian epithelial cancer
(Appendix Fig. 1). This framework was built around the
principle or Foverarching question_ Fdoes surgical specialty
influence survival in patients being operated on for newly
diagnosed ovarian epithelial cancer?_ The population of
interest was women with newly diagnosed ovarian
epithelial cancer in whom initial management was
surgical. The intervention of interest was the type of
surgeons operating on patients and included general
surgeons (GS), general gynecologists (GYN), and gynecologic
oncologists (GO). The principle outcomes of interest
were median and 5-year overall survival. Additional
outcomes important to the analysis included degree of
cytoreduction and proportion of patients with optimal
cytoreduction.
To facilitate the stage-dependent surgical approach to
ovarian cancer, the analytic framework was divided into two
parts: part 1 representing patients with advanced disease
requiring cytoreduction and part 2 representing patients with
early disease requiring accurate staging.
The goal of Part I of the framework was to address the
question Fdo patients with advanced stage ovarian epithelial
cancer who receive upfront surgical debulking have
different survival rates when operated on by GO, GYN, or
GS?_ The analytic framework for Part 1 also examined the
link between patients and survival by addressing two
questions:

1. Is the proportion of patients with optimal cytoreduction
influenced by surgical specialty? (Link 1)
2. Do patients who have optimal cytoreduction have an
improved survival? (Link 2)
The goal of Part II of the framework was to address
the question Fdo patients with early stage disease have
different survival when operated on by GO, GYN, or
GS?_
This part of the analysis also looked at a potential link
between patients with early stage disease and improved
survival by addressing the following questions:
1. Is the proportion of patients who receive complete or
comprehensive staging surgery influenced by surgical
specialty? (Link 1)
2. Do patients who have full staging surgery have an
improved survival? (Link 2)
The final component in each part of the framework
addressed potential adverse effects of exposure to different
types of surgeons.
Inclusion/exclusion criteria were set up to identify
articles pertinent to those components of the analytic
K.C. Giede et al. / Gynecologic Oncology xx (2005) 2 xxx –xxx


Results
Literature search
No evidence-based guidelines linking surgical specialty
with ovarian cancer outcomes were found within the
Cochrane database. The Medline search revealed 109
potential articles, of which 33 abstracts were selected for
review. Two additional abstracts were found when the
search was repeated in EMBASE, but no additional
abstracts were found in HealthSTAR.
From these 35 abstracts, 15 met the inclusion criteria for
review. Cross-referencing of existing reviews provided 3
additional studies for review. Thus, a total of 18 articles met
the inclusion criteria for review.


Discussion
The past three decades have brought advances in both the
medical and surgical management of ovarian epithelial
cancer [41]. Unfortunately, these advances have had little
impact on long-term survival [42], leaving ovarian cancer as
the leading cause of gynecologic cancer related mortality in
North America [43]. It is therefore imperative that we
understand where inroads have been made in order that we
maximize patient access to those treatments responsible for
improving outcome.

At the beginning of the 20th century, women with
ovarian cancer were operated on primarily by general
surgeons and general gynecologists [45]. It was not until
1970 that subspecialty training in gynecologic oncology was
established in the United States [46]. Such training has been
introduced even later to Europe [45,23,24]. Our review of
the relationship between surgical specialty and survival
outcome covers this transition period. In fact, several of the
studies we reviewed looked at the regional impact of
changing policies regarding the management of ovarian
cancer [23,24,26].

Guidelines and recommendations on managing patients
with ovarian cancer do exist. Although strongly advocating
that patients be treated by gynecologic oncologists, the
majority of these guidelines are not evidence-based
[12,13].

Evidence-based guidelines on the management of
patients with adnexal masses have recently been put forth
by the Society of Gynecology and Obstetrics of Canada [8].
In these guidelines, it has been recommended that all
patients with ovarian cancer have access to comprehensive
staging and optimal cytoreductive surgery. Unfortunately,
this review does not access who should perform that surgery
nor does it comment on the Fquality of evidence_ leading to
those recommendations.
We used the most recent USPSTF and CTF guidelines on
evidence-based reviews to access the internal validity of
each study reviewed [14,15]. Using this system allowed us
to make recommendations based on good quality of
evidence.
With this approach, we found good quality of evidence
demonstrating a 6- to 9-month median survival benefit for
patients operated on by gynecologic oncologists (P values
0.009 to 0.01) [23,32]. There was also good quality
evidence that the proportion of patients receiving optimal
cytoreductive surgery was significantly increased in patients
operated on by gynecologic oncologists [23,32]. Although
we did not conduct a full review of the link between
survival and degree of cytoreduction, we felt that existing
meta-analyses of this topic demonstrated that patient
populations with increased rates of optimal cytoreduction
had improved median survival rates [35,46].
For patients with early stage disease, we found good
quality of evidence to support a decreased recurrence rate
in patients receiving comprehensive staging [26]. There
was also fair quality evidence to support a 24% improved
survival rate in patients receiving comprehensive staging
by a gynecologic oncologist [27]. Furthermore, fair
quality of evidence demonstrated that gynecologic oncologists
were more likely to carry out comprehensive
staging [28].

We did not find evidence that comprehensive surgery
itself improves patient survival. Nevertheless, good data
from randomized trials clearly demonstrate the benefit of
full staging surgery [38,39]. Decreased recurrence rates and
subsequent improved survival are in large due to the ability
of comprehensive surgery to separate those patients with
true stage I disease from those with microscopic stage III
disease. It is the latter patient who benefits the most from
adjuvant chemotherapy.


Limitations
There were several limitations to our review. First, the
degree of heterogeneity among the patient populations,
surgical interventions, and reported outcomes made it
untenable to conduct a meta-analysis of the reported results.
Second, all the studies reviewed represented level II-b
evidence. However, well-designed cohort studies may be of
more value then poorly designed randomized studies [14].
That the majority of studies reviewed were conducted
by gynecologic oncologists could have led to self-interest
and publishing bias. However, the demonstration that
general gynecologists achieving higher rates of optimal
cytoreduction also had improved survival rates supports a
biological explanation for improved outcomes. Thirdly, our
review did not address the use of neoadjuvant chemo-
K.C. Giede et al. / Gynecologic Oncology xx (2005) xxx– xxx 7


Finally, the mere existence of guidelines does not
guarantee their application. Munoz et al. (1997) provided
a good review of patterns of care for women with ovarian
cancer in the United States [47], demonstrating that, even
with the existence of guidelines, only 10% of patients with
early stage disease, 71% of patients with stage III disease,
and 53% with stage IV disease received recommended
management. It is our hope that, with increasing emphasis
on evidence-based guidelines and increased physician
awareness of recommendations, these practices will change
for the better.

Conclusion

There is good level II-2 evidence demonstrating the
following:
1. Patients with advanced disease operated on by gynecologic
oncologists are more likely to receive optimal
cytoreductive surgery.
2. Patients with advanced disease operated on by gynecologic
oncologists have an improved median and overall
5-year survival.
3. Patients with advanced disease operated on by general
gynecologists can have survival equal to patients
operated on by gynecologic oncologists if rates of
cytoreduction are equal.
4. Patients with early stage disease are more likely to have
comprehensive staging when operated on by gynecologic
oncologists, allowing for better selection of patients
requiring adjuvant chemotherapy.

We conclude that patients with both advanced and early
stage ovarian epithelial cancer should be operated on by
specialists trained in Gynecological Oncology (level A and
level B recommendations based on good level II-2
evidence).