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Women's Cancer Center
Fall 1999
In this issue:
- Ovarian cancer survival impact of cytoreductive surgery
- Treatment of patients with endometrial cancer using minimally invasive surgery technology
- Recent Peer Review Publications by WCC
Dear Collegues,
The challenge of providing care to the gynecologic oncology patient in
the community setting has never been greater. As gynecologic oncology
fellowships have become an integrated part of training programs in this
country practice patterns in the community have changed to reflect this
calling for an increase in the availability of specialists. Along similar
lines patient awareness of specialists in this field has increased and
as expected rising demand has followed. Yet the underlying incidence of
gynecologic malignancies in the general population prevents a specialist
from maintaining an adequate clinical volume at a single institution resulting
in gynecologic oncologists "covering" multiple hospital staffs to the
best of their abilities. Requirements of IPA's, HMO's hospital-based medical
groups, and other "new" contractual aspects of medicine has only added
to our challenge.
The Women's Cancer Center in Northern California developed conceptually
and then in practice a means to address how to best provide care for the
gynecologic oncology patient regionally so as to maximize the number of
patients and physicians with access to sub-specialists while insuring
that appropriate postoperative care and consultation will be provided
on a daily basis. We have accomplished this by creating "true" Centers
of Excellence as local/regional hubs where particularly complex patients
are managed while caring for the more routine and vast majority of patients
at the referring physician's hospital. The implementation of this concept
has called for the development of teams of gynecologic oncologists.
New Center Opens in Modesto
The Women's Cancer Center has opened a new center in Modesto under the
direction of Babak Edraki, M.D. Dr. Edraki is Board eligible in Gynecologic
Oncology and hopes to bring to the community the ability to provide care
to the patient with gynecologic malignancy previously thought to be obtainable
only in a university setting. The Women's Cancer Center is the largest
group of gynecologic oncologists in the country and is a full-member institution
in the Gynecologic Oncology Group. In California only UCI and UCLA also
have this distinction. Our mission has and will continue to be the deliverance
of the finest care available to patients while working in conjunction
with physicians in the community. As a member of the Women's Cancer Center,
Dr. Edraki will have access to all group-wide GOG protocols and brings
special expertise in the area of minimally invasive surgery. The Women's
Cancer Center has pioneered the advancement of many of these procedures
for patients with gynecologic malignancies and results consistently demonstrate
that hospital stays and recovery can be shortened markedly while decreasing
costs.
Laparoscopic Radial Hysterectomy (Type III) with Aortic and Pelvic Lymphadenedtomy: Surgical Morbidity and Short-Term Follow-Up
SPIRTOS, N.M., EISENKOP, S.M., SCHLAERTH, J.B., AND BALLON, S.C.
WOMEN'S CANCER CENTER, PALO ALSO, CALIFORNIA
Objective
The purpose of this study was to identify and quantify surgical morbidity and provide short-term follow-up results in patients consented to undergo laparoscopic radical hysterectomy (type III) and retroperitoneal lymphadenectomy.
Design
The feasibility, safety, and surgical outcomes of a laparoscopic approach to radical hysterectomy and lymphadenectomy were determined in consecutive surgical candidates.
Materials & Methods
71 consecutive patients were consented to undergo this surgical procedure using argon beam coagulation (ABC) and endoscopic staplers. All had a Quetelet index of <35. The average age was 39.5 years (range 26-62 years). 65 patients had squamous cell carcinomas and 6 had adenocarcinomas of the cervix.
Results
All but four surgical procedures were completed laparoscopically. The average operative time was 215 minutes (range 180 to 430 minutes). The average blood loss was 250 ml. (range 50-700 ml.). One patient (1.4%) was transfused. Operative cystotomies occurred in three patients: two were repaired laparoscopically and one required laparotomy. One patient underwent laparotomy due to equipment failure. Two other patients underwent laparotomy to control bleeding sites. The average lymph node count was 34 (range 19-68). Eight patients (11.2%) had positive lymph nodes. All surgical margins were macroscopically negative but two had microscopically positive and/or "close" surgical margins. One patient developed a uretero-vaginal fistula post-operatively requiring re-operation. Follow-up has been provided on an every 3 month basis. There have been three (4.2%) documented recurrences with a minimum of two years follow-up.
Conclusions
Laparoscopic radical hysterectomy (type III) can be successfully completed in patients with early-stage cervical cancer with acceptable morbidity. Short-term follow-up validates the adequacy of this procedure at this time.
Fig. 1. Resection of cardinal ligament with use of Endo-GIA.
Fig. 2. Colpotomy started anteriorly.
Fig. 3. Laparoscopic colpotomy.
Laparoscopic Radical Hysterectomy
by Nick M. Spirtos
Over the last seven years techniques have been developed that allow a
type III radical hysterectomy to be performed using minimally invasive
techniques. In this series of 71 patients, not only have we demonstrated
an ability to carry out this procedure, but the number of recurrences
do not suggest that there will be an adverse affect regarding outcomes
due to the procedure.
We believe that there are inherent advantages of performing the radical
hysterectomy laparoscopically when compared to radical vaginal hysterectomy.
The laparoscopic approach mimics our traditional abdominal approach and,
therefore, visualization is not subject dependent. Performing the procedure
laparoscopically is not dependent on the angle of the pubic arch or parity
and does not require a paramedical epistomoty.
In summary, as instrumentation continues to improve and oncologic surgeons
gain experience, it is our opinion that as the millennium approaches,
the radical hysterectomy of the 20th century will remain just that.
The Women's Cancer Center Welcomes Dwight Chen, M.D. & Eugene Kaplan, M.D.
Dwight Chen, M.D.
After receiving his undergraduate degree at Cornell University, Dr. Chen graduated from the George Washington University School of Medecine. His Obstetrics and Gynecology residency was at Cedars-Sinai Medical Center/University of California, Los Angeles, and he completed his fellowship training in Gynecologic Oncology at the University of Minnesota. Dr. Chen is a Board certified Gynecologic Oncologist and a Fellow of the American College of Obstetrics and Gynecology. Prior to joining the Women's Cancer Center, he was an Assistant Professor in the Division of Gynecologic Oncology at the University of Minnesota. While at Minnesota, he was the Director of Gynecology-Oncology at Hennepin County Medical Center and Park Nicollet Medical Center. He has authored numerous scientific publications and has lectured both nationally and internationally on many topics in the field of gynecologic cancer. Dr. Chen is considered an expert in the management of cervix cancer as well as in the use of advanced surgical techniques in treating women with pelvic malignancies.
Eugene Kaplan, M.D.
Dr. Kaplan received his medical degree in Russia and completed his residency
in obstetrics and gynecology at Loyola University and fellowship in pelvic
surgery at Allegheny University's Graduate Hospital. Under the guidance
of Drs. Thomas V. Sedlacek and Michael J. Campion, the training focused
on the most difficult types of abdominal and pelvic gynecologic surgeries
which included radical and modified radical hysterectomies, radical vulvectomies,
total pelvic exenterations and ovarian cancer cytoreductive surgeries.
His curriculum at Graduate also consisted of all aspects of advanced endoscopic
surgeries including LAVH's, laparoscopic lymph node dissections, and numerous
hysteroscopic procedures.
Dr. Kaplan's second year of training was under the mentorship of Dr. Marvin
H. Terry Grody in the Urogynecology-Pelvic Reconstructive Surgery Fellowship
at Temple University in Philadelphia.
Dr. Kaplan will see patients in the San Ramon and San Francisco offices
providing urogynecologic services and pelvic reconstructive surgery throughout
the East Bay and San Francisco areas.
Practice Update: Complete Cytoreductive Surgery is Feasible and Maximizes Survival in Patients with Advanced Epithelial Ovarian Cancer
A Prospective Study
S.M. EISENKOP, M.D.; R.I. FRIEDMAN, M.D., PH.D.; H.J. WANG, M.P.H.
Objective
Despite correlation between the completeness of surgical cytoreduction and survival for patients with advanced ovarian cancer, relatively few undergo complete cytoreduction. This study was initiated to prospectively determine the ability to surgically eliminate all visible disease in patients with stage IIIC and IV epithelial ovarian cancer and the associated impact of survival.
Methods
Between 1990 and 1996, 163 consecutive patients underwent primary cytoreduction. The goal was the excision or ablation of all visible disease prior to initiation of systemic platinum-based combination chemotherapy. A multivariate analysis determined which clinical and pathologic variables influenced the probability of achieving complete cytoreduction (logistic regression) and survival (Cox proportional hazards model).
Results
One hundred thirty-nine patients (85.3%) underwent removal of all visible tumor, 22 (13.5%) had cytoreduction to 1 cm residual disease, and 2 (1.2%) had unresected bulky disease. The median and estimated 5-year survival for the entire cohort was 54 months and 48%, respectively. The probability of achieving complete cytoreduction was influenced independently by the pre-operative Gynecologic Oncology Group performance status (0-1 vs. 2-3, p = 0.004), the number of mesenteric and intestinal serosal implants (75 implants, P = 0.005), and stage (IIIC vs. IV, P = 0.006). The probability of survival was independently influenced by age (61 years, P + 0.003), volume of ascites (1 liter, P = 0.01), stage (IIIC vs. IV, P = 0.004), histology (clear cell and mucinous vs. all other, P = 0.03), and the completeness of cytoreductive operation (complete vs. incomplete cytoreduction, P = 0.02).
Conclusions
Complete cytoreduction is possible for the majority of patients and improves
survival, even compared to operations with minimal (</=1cm) residual disease.
Unless their medical condition prohibits anesthesia and surgery, patients
with advanced epithelial ovarian cancer should undergo primary cytoreductive
surgery with the intention of complete tumor removal.
Gynecologic Oncology 69: 103-108 (1998) Article No. GO984955
Women's Cancer Center Research Foundation Approved
The Women's Cancer Center recently had its foundation approved. The foundation
will be dedicated to funding clinically applicable research as well as
establishing centers in the community that will hopefully function as
both an information center as well as a meeting place for women with cancer.
For more information, please call Michael Seeley at (650) 326-6503
Ovarian Cancer Survival Impact of Cytoreductive Surgery
Cytoreductive surgery, or tumor debulking, has been advocated for the treatment of women with advanced epithelial ovarian cancer for nearly two decades. Patients with stage III and IV epithelial ovarian cancer from the 1970's and 80's who had cytoreductive surgery that accomplished resection of all metastases >2 centimeters in greatest cross sectional dimension had better longevity than patients with bulkier residual disease. Although patients who were visibly disease-free survived the longest, cytoreductive operations resulting in < 1-2 centimeters of unresected disease were defined as optimal outcomes because most patients had residual peritoneal metastatic implants, and often had extensive unresected pelvic and upper abdominal disease due to massive contiguous growth, bulky retroperitoneal lymphadenopathy, and confluent disease on the diaphragm.Over the last decade surgical procedures have been described that theoretically permit excision of all visible disease for the vast majority of patients. Women's Cancer Center physicians have innovated a procedure called the modified posterior pelvic exenteration that permits massive pelvic disease involving the reproductive organs, pelvic peritoneum, and recto-signoid colon to be excised while maintaining normal rectal function.1 They also have proven the benefit of debulking grossly involved aortic lymph nodes and ablating widespread peritoneal metastases using the Argon Beam Coagulator.2,3
Our experience with the management of women with the most advanced cases of epithelial ovarian cancer at the Women's Cancer Center in Encino-Tarzana was recently published.4 163 consecutive women with stage IIIC and IV disease were operated on. Our approach was unique in that we were willing to utilize all described techniques in an attempt to render patients to be visibly disease-free rather than the accepted traditional outcome of < 1-2 centimeters of unresected disease. We were able to accomplish resection of all visible disease for 139 (85%) patients and 161 (98.8%) had < 1 centimeter of residual disease. Previously only 10-30% of other overall study groups were reported to be visibly disease-free after cytoreduction.
The accomplishment of complete cytoreduction for patients who would have had unresected disease if operated on with conventional strategy would be irrelevant if these outcomes failed to translate into improvements in survival. Some investigators have speculated that successful resection reflects comparatively less biological aggressiveness rather than increased operative effort, and add that differences in tumor biology account for perceived survival benefits from cytoreductions. The overall median and 5-year estimated survivals (54 months and 48%) from the current series exceed all previously published outcomes. The 85% of patients in this series that had complete cytoreduction survived longer than those having conventional (< /=1-2 cm residual disease) cytoreduction in other series. The 62 month median survival and 52% estimated 5-year survival for disease-free patients in the current series compare favorably to median (40-70 months) and estimated 5-year (40-75%) outcomes of selected patients with lesser tumor burdens undergoing complete resection. Most importantly, our series establishes that survival benefits from complete cytoreductions previously reported for small percentages of overall series are reproducible for large groups of unselected patients who undergo complete cytoreduction, and that the impact of innate biological aggressiveness of many tumors can be offset, and in some cases negated with complete cytoreduction.
It is our hope that this landmark manuscript will dramatically change the manner in which women with advanced ovarian cancer are operated on nationwide, and that their prognosis for survival may be further improved when truly maximal operative effort is combined with future adjunctive treatment strategies yet to be developed in the biotechnology industry.
References
1. Eisenkop, S.M.; Nalich, R.H.; Tong, N.N.H. Modified posterior exenteration
for ovarian cancer. Obstetric Gynecology 78:879-885 (1991)
2. Eisenkop, S.M.; Nalich, R.H.; Wang, H.; Teng, N.N.H. Peritoneal implant
elimination during cytoreductive surgery for ovarian cancer: Impact of
survival. Gynecologic Oncology 51:224-229 (1993).
3. Spirtos, N.M.; Gross, G.M.; Freddo, L.; et al. Cytoreductive surgery
in advanced epithelial cancer of the ovary: The impact of aortic and pelvic
lymphadenectomy. Gynecologic Oncology 56:345-352 (1995).
4. Eisenkop, S.M.; Friedman, R.L.; Wang, H. Complete cytoreductive surgery
is feasible and maximizes survival in patients with advanced epithelial
ovarian cancer: A prospective study. Cynecologic Oncology 69: 103-106
(1998).
Gynecologic Oncology Group Open Protocols
Endometrium:
GOG #122: Whole abdominal radiotherapy vs. combination doxurubicin-cisplatin
chemotherapy in advanced endometrial carcinoma, a quality of life companion
study to GOG #122 (Phase III)
GOG #137:A randomized double-blinded trial of estrogen replacement
therapy vs. placebo in women with stage I or II endometrial adenocarcinoma.
GOG #167: A two-part study of the treatment of atypical endometrial
hyperplasia. Part A: A prospective study of immediate hysterectomy. Part
B: A randomized phase II study of medroxyprogesteron acetate vs. depoprovera.
GOG #177:A randomized study of doxurubicin + cisplatin vs. doxorubicin
+ cisplatin + 3-hour paclitaxel with G-CSF support in patients with primary
stage II & IV or recurrent endometrial carcinoma, phase III.
GOG #LAP2: A phase III randomized clinical trial of laparoscopic
pelvic and para-aortic node sampling with vaginal hysterectomy and BSO
vs. open laparotomy with pelvic and para-aortic node sampling and abdominal
hysterectomy and BSO in uterine sarcomas and endometrial adenocarcinoma,
clinical stage I, IIA, grades I, II, III.
Cervix:
GOG #127N: A randomized phase II evaluation of bryostatin in persistent
or recurrent non-squamous cell carcinoma of the cervix, phase II.
GOG #128E:Evaluation of vinorelbine (Navelbine) in persistent or
recurrent non-squamous cell carcinoma of the cervix, phaseII.
GOG #141: Treatment of patients with suboptimal ("bulky") stage
IB carcinoma of the cervix: A randomized comparison of radical hysterectomy
and pelvic and para-aortic lymphadenectomy with or without neoadujvant
VCR and cesplatin chemotherapy (phase III).
GOG #150: A phase III randomized study of whole abdominal radiotherapy
(WAR) vs. combinations ifosfamide-masna with cisplatin in optimally debulked
stage I, II, III or IV carcinosarcoma (CS) of the uterus (also cervical
sarcoma).
GOG #165: A randomized comparison of radiation plus weekly CDDP
vs. radiation plus PVI (Protracted Venous Infusion) 5-FU in patients with
stage IIB, IIIB, and IVA carcinoma of the cervix.
GOG #171:Expression of the MN protein in atypical glandular cells
of undetermined significance (AGUS or ACCUS) as a potential diagnostic
biomarker of cervical dysplasia/neoplasia, phase II.
Uterus:
GOG #130D: Evaluation of topotecan in the treatment of persistent
or recurrent carcinosarcoma (mixed mesodermal tumors) of the uterus, phase
II.
GOG #150:A phase III randomized study of whole abdominal radiotherapy
(WAR) vs. combination ifosfamide-mesna with cisplatin in optimally debulked
stage I, II, III, or IV carcinosarcoma (CS) of the uterus (also cervical
sarcoma).
GOG #161: A phase III trial of ifosfamide vs. ifosfamide plus paclitaxel
in patients with advance, persistent or recurrent carcinosarcoma (mixed
mesodermal tumor) of the uterus.
Ovary:
GOG #125I: Phase II evaluation of aminocampatothecin (9AC) in
recurrent, plat-resistant and refractory ovarian and primary peritoneal
carcinoma.
GOG #133: A randomized trial of adjuvant intraperitoneal recombinant
interferon alpha-2 in stage III ovarian carcinoma inpatients who have
no evidence of disease after surgery and chemotherapy, phase III.
GOG #152: A phase III randomized study of cisplatin and Taxol with
interval secondary cytoreduction vs. cisplatin and Taxol. in Patients
with suboptimal stage III epithelial ovarian carcinoma.
GOG #162: A phase III randomized trial of cisplatin with paclitaxel
administered by either 24-hour infusion or 96-hour infusion in patients
with selected stage III and stage IV epithelial ovarian carcinoma.
GOG #172: A phase III randomized trial of intravenous paclitaxel
and cisplatin vs. intravenous paclitaxel intraperitoneal cisplatin and
intraperitoneal paclitaxel in patients with optimal stage III epithelial
ovarian carcinoma and primary peritoneal carcinoma.
GOG #175: A randomized phase III trial of IV carboplatin (AUC 6)
and paclitaxel 175 mb/m2 q 21 days x3 courses plus low dose paclitaxel
40 mg/m2 vs. IV carboplatin (AUC 6) and paclitaxel 175 mg/m2 q 21 days
x3 courses plus observation in patients with early stage ovarian carcinoma.
GOG #9302: Laparoscopic staging in patients with incompletely staged
cancer of the ovary, primary fallopian tube carcinoma and primary peritoneal
carcinoma.
Vulvar:
GOG #173: Intraoperative lymphatic mapping in patients with stage I and II squamous carcinoma of the vulva.
Fertility Conservation in Patients with Early-Stage Cervical Cancer
NICK M. SPIRTOS, M.D. AND JOHN B. SCHLAERTH, M.D. WONEN'S CANCER CENTER, PALO ALTO, CALIFORNIA
May 23, 1999, Linda Leeper gave birth to Scott Leeper. Scott was the
first infant in the United States delivered following a fertility-sparing
procedure performed with curative intent for patients with invasive cervical
cancer (Stage I to IIA). As previously reported in the WCC newsletter
in the winter of 1997, radical trachelectomy was first performed in France
with early results suggesting this procedure was associated with reasonable
risk and favorable outcome without sterilization of patients desirous
of maintaining their reproductive organs. Since that report, physicians
at the WCC have performed 16 radical trachelectomies and lymph node dissections.
Surgery was performed in conjuction with Dr. William "Buzz" Brown at Community
Hospital of Los Gatos on September 22, 1997. The surgery, although technically
complex, was uncomplicated. Within approximately a year, without assisted
reproductive technology, Mr. And Mrs. Leeper conceived. At approximately
28 weeks gestation, premature rupture of the membranes occurred resulting
in a cesarean section performed by Dr. Martin Silverman, Dr. Brown's partner,
in May of 1999. Scott weighs 7 lb. and is a picture of good health, as
is his mom.
As this is a new procedure and only a small number of patients are available
for follow-up, radical trachelectomy should be carefully considered as
one option for patients intent on maintaining their reproductive organs.
In our next issue, Dr. Schlaerth and Spirtos will provide a more complete
discussion of this procedure and the experience at the Women's Cancer
Center.
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