Download Ovarian Cancer Staging

Ovarian Cancer Staging
Liz Y. Han, MD, and Robert L. Coleman, MD
P
rimary malignancy of the ovary is fortunately a relatively
uncommon condition. In 2007, an estimated 22,430 new
cases and 15,280 deaths are expected.1 However, the number
of women who succumb to this disease eclipses the total
contribution of all other distinct gynecologic cancers combined, distinguishing it as the most lethal. Histologically, the
most common form of the disease is epithelial, accounting for
more than 80% of primary malignant diagnoses. However,
ovarian cancer may also arise from the germ cells, ovarian
stroma, and other supporting tissues. In addition, a sizeable
proportion of younger women with ovarian cancer will have
a proliferative, but noninvasive element designated as “low
malignant potential” or “borderline” epithelial ovarian tumor. Individual risk factors and therapeutic options for these
subtypes are important to clearly distinguish given their occurrence in women of reproductive potential and unique
natural history.
The focus of this contribution will center on the management and care of patients with epithelial ovarian cancer;
however, surgical approaches to staging of these rarer ovarian
cancers are similar in the absence of desired fertility preservation. A brief outline of these considerations appears at the
end of this discussion.
Although the incidence of ovarian carcinoma ranks second
in all malignancies of the female reproductive tract, it remains
the most deadly. Risk factors for epithelial ovarian carcinoma
are well established. Although pregnancies and oral contraceptive use are protective, age is the strongest patient-related
risk factor. Overall, it is estimated that 1 in 70 women will
develop ovarian cancer in their lifetime with age-specific incidence peaking at 75 to 80 years of age.2 This is especially
startling considering the aging population of the United
States. Furthermore, a family history of ovarian cancer, breast
cancer, or both, is the second strongest risk factor. Women
who are heterozygous for mutations of either BRCA 1 or
BRCA 2 have an estimated lifetime risk of 16% to 60%.3 Other
risk factors may also include nulliparity, involuntary infertility, early menarche, and late menopause.2
Failure of early detection is the principle reason behind
ovarian carcinoma’s high mortality. More than 90% of
From the Department of Gynecologic Oncology, The University of TexasM.D. Anderson Cancer Center, Houston, TX.
Address reprint requests to Robert L. Coleman, MD, Professor, Director of
Clinical Research, The University of Texas-M.D. Anderson Cancer Center, Department of Gynecologic Oncology, 1155 Herman Pressler,
CPB6.3244, Unit 1362, Houston, TX 77030. E-mail: RColeman@
mdanderson.org.
1524-153X/07/$-see front matter © 2007 Elsevier Inc. All rights reserved.
doi:10.1053/j.optechgensurg.2007.08.002
women diagnosed with ovarian cancer have symptoms antedating the diagnosis by several months, however, these are
often vague (abdominal bloating, pelvic pressure, urinary
dysfunction, etc.) contributing to a delayed diagnosis.4 CA125 has proven to be an excellent marker of surveillance for
treatment response; however, its diagnostic value is yet to be
proven. Seventy-five percent of this malignancy is diagnosed
in advanced stages when the disease has spread beyond the
pelvis.1,5 The 5-year survival for these patients is only 30% to
40%.6 These factors underlie the importance of not only early
detection, but also proper surgical staging and optimal disease debulking with subsequent adjuvant chemotherapy to
maximize survival potential.
In general, the surgical principium of ovarian cancer is
accurate staging for limited disease and cytoreduction for
advanced or metastatic disease. Surgical staging in the absence of visible metastatic spread requires broad and directed
sampling of “at-risk” tissues sufficient to assign an appropriate stage in accordance with FIGO guidelines (Table 1). In
the presence of more advanced disease, surgical extirpation is
undertaken to remove the primary site of disease and levy the
greatest impact on tumor burden. Frequently this is referred
to as performing an “optimal cytoreduction” procedure.
The definition of optimal cytoreduction in ovarian carcinoma remains controversial, although the most widely accepted is residual disease less than 1 cm.7 The survival advantage gained from debulking was first described by Meigs
in 1934,8 and explored in a systematic fashion by Griffiths in
1975 where longer survival is associated with lesser residual
disease.9 Since then, the survival advantage of optimal debulking is further proven retrospectively by various authors;
in fact, Bristow and co-workers demonstrated that for each
10% decrease in residual tumor volume, there is a 5.5%
increase in median survival.10,11
Currently, there is a trend to establish optimal cytoreduction as no visible residual disease. Published studies have
demonstrated that prognosis is directly related to number of
residual implants as well as volume of residual disease.12,13
Various series reflect optimal cytoreduction is obtainable in
approximately 20% to 25% of patients presenting with advanced ovarian cancer.14,15 Furthermore, in GOG trials examining primary cytoreduction and adjuvant chemotherapy,
patients with no visible residual disease had the best prognosis for survival.6,16,17 Therefore, some authors have concluded that all efforts including resection, ablation, aspiration of all visible disease as allowed by medical status and
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Table 1 Ovarian Cancer Staging by FIGO Criteria (1986)
I. Growth limited to the ovaries
IA. Tumor limited to one ovary; capsule intact, no tumor
on ovarian surface; no malignant cells in ascites or
peritoneal washings
IB. Tumor limited to both ovaries; capsules intact, no
tumor on ovarian surface; no malignant cells in
ascites or peritoneal washings
IC. Tumor limited to one or both ovaries with any of the
following: capsule ruptured, tumor on ovarian surface; malignant cells in ascites or peritoneal washings
II. Tumor involves one or both ovaries with pelvic
extensions
IIA. Extension and/or implants on uterus and/or tube(s);
no malignant cells in ascites or peritoneal washings
IIB. Extension to other pelvic tissues; no malignant cells
in ascites or peritoneal washings
IIC. Pelvic extension with malignant cells in ascites or
peritoneal washings
III. Tumor involves one or both ovaries with peritoneal
metastasis outside the pelvis and/or retroperitoneal or
inguinal node metastasis
IIIA. Microscopic peritoneal metastasis beyond pelvis
IIIB. Macroscopic peritoneal metastasis beyond pelvis 2
cm or less in greatest dimension
IIIC. Peritoneal metastasis beyond pelvis more than 2
cm in greatest dimension and/or regional lymph
node metastasis
IV. Distant metastasis (excludes peritoneal metastasis) to
liver parenchyma or malignant pleural effusion
intraoperative patient stability should be performed to
achieve complete cytoreduction.18
Ovarian Carcinoma Staging
Preoperative Evaluation and Considerations
Preoperative imaging with computed tomography (CT) scan
is most helpful in initial evaluation of disease spread. In addition, CT findings such as diffuse disease sites and peritoneal thickenings may be predictors of suboptimal debulking.19-22 Other predictors for suboptimal debulking include
preoperative CA-125 level greater than 500.23 In patients
with extensive disease and elevated CA-125 with multiple
comorbidities, neoadjuvant chemotherapy may be another
option.
Published retrospective data revealed that up-front chemotherapy can reduce morbidity and mortality while offering higher rates of optimal interval cytoreduction without
survival compromise.24,25
Ovarian Carcinoma Staging
After appropriate preoperative medical and anesthesia assessment, patients requiring formal staging or cytoreduction
should undergo exploration with laparotomy. Incidental
early stage ovarian cancers discovered during laparoscopic
evaluation of an adnexal or pelvic mass may be staged via
laparoscopy as long as the same procedure and staging biopsies can be obtained including retroperitoneal lymph nodes.
L.Y. Han and R.L. Coleman
The debulking procedure begins generally with a midline
vertical skin incision from the level of the pubic symphysis
extending cephalad around the umbilicus to a point felt sufficient to evaluate the upper abdomen and diaphragmatic
peritoneum. We generally prefer extension around the right
side umbilicus or directly through the umbilicus, in case a
diverting colostomy is necessary as part of the cytoreduction
procedure. The abdomen is then opened to the peritoneum
with care exercised inferiorly to avoid injury to the bladder. If
a patient has massive ascites, drainage at the most ventral
aspect of the abdomen before opening is prudent. In the
absence of ascites, 100 to 150 mL of sterile saline is used to
obtain washings from the pelvis, paracolic gutters, and diaphragm bilaterally. This fluid should be sent for permanent
cytological evaluation.
At this point, a survey of the abdomen and pelvis is performed to evaluate the disease extent. A methodical and thorough system should be adopted in this evaluation to encompass the following: upper abdomen including the liver
surface, gall bladder, dome of the diaphragm bilaterally, the
stomach, pancreas, and retroperitoneally, the kidneys. The
small bowel is examined from the cecum to the ligament of
Treitz, paying attention to both serosal disease as well as
mesenteric involvement, and same technique is applied to
the large bowel survey. The entirety of the peritoneal surface,
including the paracolic gutters should be palpated for disease
presence. The omentum is fanned out for visual inspection.
Next, the pelvic organs such as ovaries, fallopian tubes and
uterus, including the anterior and posterior cul-de-sacs,
rectosigmoid, are evaluated.
What appears to be early stage ovarian carcinoma (ie,
stages I and II) by initial abdominal and pelvic survey merit
additional peritoneal and lymph node biopsies as information gained may upstage the diagnosis in 25% of cases.26
Random peritoneal biopsies should be performed in the pelvis and abdomen, including the paracolic gutters. The most
manageable approach is completed using pickups and Metzenbaum scissors to excise the peritoneum in the locations
listed and applying electrocautery for hemostasis (Fig 1).
Lymph node biopsies are obtained from the pelvis as well as
the para-aortic regions. Pelvic lymphectomy begins with adequate exposure of the external iliac vessels (Fig 2). The nodal
bundle straddling the vessels can be peeled away using a combination of sharp dissection with the Metzenbaum scissors and
hemo-clips to occlude the arterioles and venules to achieve hemostasis. The external iliac vein is then retracted laterally with
exposure of the obturator space that allow for collection of additional nodal tissue whereas carefully dissecting the obturator
nerve. The retroperitoneum dissection is then extended superior and medially with electrocautery, carefully avoiding the ureter as it courses over the common iliac vessels, and retracted
laterally to allow for adequate visualization (Fig 3 A, B). The
inferior mesenteric artery is then isolated approximately 3 cm
superior to the aortic bifurcation and the nodal bundle around
the aorta is retrieved in a similar fashion. The superior border of
this dissection is the renal vein.
Routine appendectomy is not indicated in ovarian staging.
However, if frozen section returns with a diagnosis of mucinous tumor of the ovaries, 8% of the appendices are involved;
therefore, appendectomy should be performed.27 Liver resection and splenectomy are not part of ovarian cancer staging;
Ovarian cancer staging
Figure 1 (A, B) Suggested location of tissue biopsies required for systematic evaluation for metastatic disease, based on
theorized flow of metastatic cells in abdominal cavity.
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L.Y. Han and R.L. Coleman
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Figure 2 Adequate sampling of lymphatic tissues in the pelvis should include four areas: obturator, external iliac,
junctional, and common iliac nodes.
therefore, should only be performed as part of a radical debulking with a feasible aim for optimal cytoreduction.
Total Abdominal
Hysterectomy With Bilateral
Salphino-Ophorectomy and Omentectomy
The core of ovarian carcinoma staging involves total abdominal hysterectomy and bilateral salphino-ophorectomy, followed by omentectomy (see “Hysterectomy” elsewhere in
this issue). As tumors often distort the anatomy and generate
dense adhesions, restoration of normal anatomy is paramount before starting any procedure. Furthermore, careful
isolation of the ureter from the beginning provides tremendous advantage.
Once adequate exposure of the pelvis is obtained, Kelly
clamps are then placed on the uterine cornua bilaterally to
apply traction during the procedure. The round ligaments
are identified and suture ligated with absorbable sutures and
transected. This step allows the division of the anterior and
posterior leaflets of the broad ligament that provides an entry
into the retroperitoneal space where on clearance of the areolar tissues, the ureter is found along the medial surface of the
broad ligament. A small window is made in an avascular
space of the broad ligament to isolate the infundibular pelvic
(IP) ligaments encompassing the ovarian vessels. The IP
ligaments then are double clamped, suture ligated and
transected.
The anterior leaflet of the broad ligament is then incised
inferiorly along the uterine contour then the bladder reflection to construct a bladder flap. The bladder is then gently
dissected off the lower uterine segment as well as the cervix.
Cephalad traction on the uterus facilitates this process. The
uterine vessels are skeletonized, clamped, transected, and
ligated. The cardinal and uterosacral ligaments are sequentially clamped, transected, and stitched followed by the complete amputation of the uterus with intact cervix using Jorgensen scissors. The vaginal cuff is then reapproximated
using a series of figure-of-eights. Vaginal cuff hemostasis is
vital as it is one of the most common site of postoperative
hemorrhage.28 Occasionally, the pelvis structures present as a
diffuse amalgamation incorporating bladder peritoneum,
uterus, fallopian tubes, and ovaries as well as the sigmoid
colon. This may be effectively accomplished through modified posterior exenteration procedure described below.29
The omentum is then fanned out and its attachments to the
transverse colon are identified (Fig 4 A-C). The posterior
leaflet of the omentum is then incised with electrocautery,
and an avascular space between the omentum and the transverse mesocolon is developed superiorly to the level of the
lesser sac by finger dissection. Along the greater curvature of
the stomach, the omental side of the gastroepiploic and its
anastomotic short gastric vessels are isolated and transected
with linear dissecting stapler to free the entire omentum.
Special Surgical Considerations
The abdominal and pelvic survey renders a diagnosis of stage.
In advanced ovarian carcinoma (ie, stages III and IV), what
ensues this evaluation is the decision making process to determine whether an optimal cytoreduction can be achieved.
Optimal cytoreduction rates are varied and dependent on
tumor volume and location.30 The possible morbidity incurred from a radical debulking procedure should be balanced against the survival benefits gained from an optimal
debulking; however, if optimal disease resection cannot be
achieved, then radical surgery fails to be justified as prognosis
is uninfluenced by residual disease greater than 2 cm.11
Ovarian cancer staging
Figure 3 (A, B) Paraortic node sampling should include tissue from below and above the level of the inferior mesenteric
artery bilaterally.
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Figure 4 (A-C) The omentum can contain a substantial amount of metastatic disease. In cases of no visible disease, it
represents a large surface area for early implantation underscoring its importance in surgical staging. Supracolic
resection is often necessary for bulky omental disease.
Many have commented on the radicality of ovarian cancer
debulking to achieve optimal cytoreduction, especially in
bulky stage IIIC and IV diseases. Patients may require extensive upper abdominal organ resections such as diaphragm
peritonectomy or full-thickness resection, splenectomy with
or without distal pancreatectomy, cholecystectomy for gallbladder surface tumor or resection of parenchymal liver or
porta hepatic disease in addition to possible ablative upper
abdominal procedures using electrocautery, Cavitron ultrasonic aspirator (CUSA) or argon-beam coagulator (ABC).31
Moreover, patients may also exhibit extensive tumor spread
in the pelvis, often involving the rectosigmoid and the
cul-de-sac where a modified posterior exenteration and low
rectal anastomosis must be performed.29
Isolated diaphragmatic tumors can often to be ablated.
However, extensive diaphragmatic disease can be removed
by stripping the peritoneum away from the muscle, and more
invasive implants often require full thickness resection with
repair. Postoperative complications often include pneumothorax and symptomatic pleural effusion that necessitate medical
interventions (see “Surgical Management of Diaphragm Disease
in Ovarian Cancer” elsewhere in this issue).32
Superficial splenic metastasis can be ablated, and splenectomy is performed for the following indications: (1) involvement of the splenic surface, hilum, and/or vasculature with
bulky disease contiguous with omental metastases; (2) isolated or confluent hilar and/or capsular metastases that could
not be resected, ablated, or aspirated; and (3) parenchymal
metastases.33 The gastrosplenic and splenorenal ligaments
are divided and separated from the spleen at the level of the
splenic flexure of the colon, and its vessels are clamped, cut
and ligated with absorbable sutures. If disease is involved in
the hilum and the pancreatic tail, the distal pancreas is mobilized with electrocautery as well. The splenic artery and vein
are then dissected away from the pancreas and clamped, cut and
ligated. The pancreas is then divided with a linear stapler.33
Ovarian cancer staging
59
the paravesical and pararectal spaces. The lateral ligaments
can then be serially ligated close to the pelvic sidewall with
the specimen on cephalad traction. The vagina and rectum
are transected at the level of the levator muscle and above the
levator sling, respectively. The rectum can then be processed
for anastomosis with a mobilized descending colon using an
automatic surgical stapler.34 A diverting ileostomy may be
indicated if the anastomotic suture line is felt to be tenuous.
Nonepithelial and Low
Malignant Potential Tumors
Approximately 15% of ovarian malignancies occur in women
of reproductive age, therefore, special consideration must be
given to fertility sparing surgical approaches such as unilateral cystectomy and oophorectomy in the setting of proper
staging with cytology and multiple pelvic and abdominal
biopsies.35 Ovarian germ cell tumors (with the exception of
dysgerminomas) are almost always unilateral, therefore,
preservation of the contra-lateral ovary and uterus is often
feasible.36 Approximately 80% of juvenile granulose cell tumors, a subset of sex cord stromal ovarian carcinoma, is
diagnosed in women under 20 years of age.35 Considering
that 95% of this type of tumor is unilateral, and confined to
the ovaries at time of diagnosis, this tumor type can be appropriately treated with conservative measures as well.
Low malignant potential (LMP) tumors of the ovary typically is found in younger women when compared with their
epithelial ovarian carcinoma counterparts, and account for
15% of all epithelial ovarian carcinoma, and has a 10-year
survival of 90%.37 For both serous and mucinous LMP tumors, 60% and 90% of cases are confined to one ovary,
therefore, affording the opportunity for fertility sparing surgeries.35 However, because LMP tumors are often diagnosed
on permanent sections for pathological evaluation, a management dilemma arises as to the clinical relevance of restaging.
Retrospective data have shown that patients with provisional
stage IA disease are upstaged 7% to 15% when re-operated
for complete diagnosis, and current recommendations remains conflicting.38,39 However, serous histology and initial
cystectomy are two risk factors that contribute to upstaging
and patients with these risk factors should be considered for
re-exploration.
Figure 5 Pelvic disease may be extensive, including the cul-de-sac
and recto-sigmoid. A modified posterior exenteration and rectosigmoidectomy may be necessary.
Conclusion
For contiguous tumor involvement of the cul-de-sac and
the rectosigmoid, a modified posterior exenteration and low
rectal anastomosis may be necessary (Fig 5 A, B).33 The procedure begins with bilateral opening the peritoneum covering the rectosigmoid colon to mobilize the colon. Care is
taken to preserve the ureters. A linear stapler is then applied to
the rectosigmoid colon slightly below the sacral promontory.
The rectum is then dissected away from the sacrum to the coccyx, and the rectal stalk is sequentially ligated and transected
from its lateral attachments. The hysterectomy is performed as
previously described with the exception that the ureters are
cleared from the cardinal web bilaterally, and the combination of the uterine and rectal dissections allows for opening of
Proper ovarian staging provides vital information in terms of
patient diagnosis and prognosis. Published studies have
demonstrated that survival of women with advanced ovarian
carcinoma is improved when the primary surgery is performed by gynecologic oncologists versus general gynecologists or surgeons.40-42 A recently published study examined
proper staging techniques for early stage ovarian carcinoma,
and found that significantly more gynecologic oncologists are
likely to perform lymph node dissection than general gynecologists and surgeons. Furthermore, patients treated by gynecologic oncologists had better outcomes compared with
their counterparts treated by generalists.43 Nonetheless, hospital and surgeon specific procedure volumes are not strong
predictors of survival outcomes after surgery for ovarian cancer among older women.44 As cytoreduction is intimately
L.Y. Han and R.L. Coleman
60
intertwined in this surgical staging process, appropriate referral to a gynecologic oncologist is often indicated.
22.
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