C.Paul Morrow

Surgical pathologic spread patterns of endometrial cancer: A gynecologic oncology group study

The surgical pathologic features of 621 patients with Stage I carcinoma of the endometrium are presented. All patients were treated with primary surgery consisting of total abdominal hysterectomy, bilateral salpingo‐oophorectomy, selective pelvic and paraaortic lymphadenectomy and peritoneal cytology. An appreciable number of patients (144—22%) with Stage I cancers have disease outside of the uterus (lymph node metastasis, adenexal disease, intraperitoneal spread and/or malignant cells in peritoneal washings). Multiple prognostic factors particularly grade and depth of invasion are related to extrauterine disease. This study adds credence to the primary surgical approach with individualized postoperative therapy as indicated.

Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: A gynecologic oncology group study

Abstract Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology [adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR=8.1; all adenocanthomas, RR=1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0% vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients. These data seem to implicate malignant cytology as a serious adverse finding, especially with respect to the risk for regional/distant and abdominal failure.

Classification of radical hysterectomy

Since the first publications about surgery for cervical cancer, many radical procedures that accord with different degrees of radicality have been described and done. Here, we propose a basis for a new and simple classification for cervical-cancer surgery, taking into account the curative effect of surgery and adverse effects, such as bladder dysfunction. The international anatomical nomenclature is used where it applies. For simplification, the classification is based only on lateral extent of resection. We describe four types of radical hysterectomy (A-D), adding when necessary a few subtypes that consider nerve preservation and paracervical lymphadenectomy. Lymph-node dissection is considered separately: four levels (1-4) are defined according to corresponding arterial anatomy and radicality of the procedure. The classification applies to fertility-sparing surgery, and can be adapted to open, vaginal, laparoscopic, or robotic surgery. In the future, internationally standardised description of techniques for communication, comparison, clinical research, and quality control will be a basic part of every surgical procedure.

Pathologic models to predict outcome for women with endometrial adenocarcinoma: The importance of the distinction between surgical stage and clinical stage - A Gynecologic Oncology Group Study

Numerous pathologic factors have been identified as important in predicting outcome for women with endometrial adenocarcinoma. However, most patients have a mixture of good and bad factors. For these women, the prognosis is uncertain, and it is often unclear whether postoperative therapy is indicated.

Radical vaginal trachelectomy and pelvic lymphadenectomy for preservation of fertility in early cervical carcinoma

OBJECTIVE The aim of this study was to examine our experience with radical vaginal trachelectomy in women with early cervical cancers who desire to maintain fertility. METHODS Women who underwent radical vaginal trachelectomy with pelvic lymphadenectomy over a 6-year period are the basis of this report. Subjects were selected for this treatment on the basis of favorable cervical tumors and a desire to maintain fertility. All subjects were informed that this therapy did not represent standard treatment for early stage cervical cancer. Obstetrical and oncologic outcomes were evaluated. RESULTS Twenty-one women underwent this procedure. The median age was 30 years (range 23-41); 14 were nulligravid and 16 were nulliparous. Mean tumor diameter was 1.1 cm (range 0.3-3.0). Mean operative time was 318 min, with a mean blood loss of 293 cc, and average hospital stay was 3 days. Three patients had transient neuropathy postoperatively. No patient required laparotomy. Two patients had completion of radical vaginal hysterectomy for an inability to clear the cancer with trachelectomy and 1 had postoperative radiation for high-risk features on final pathology. With an average follow-up of 31.5 months, there have been no recurrences. Three women have become pregnant: 1 woman delivered twins at 24 weeks, 1 woman delivered a singleton at term, and 1 patient had rupture of membranes and chorioamnionitis at 20 weeks gestation. CONCLUSIONS Radical vaginal trachelectomy with pelvic lymphadenectomy permits preservation of fertility in selected patients. To date, with more than 150 cases reported in the literature, recurrence rates are comparable to those seen with radical hysterectomy.

Adenocarcinoma of the endometrium: its metastatic lymph node potential. A preliminary report.

Abstract Stage I adenocarcinoma of the endometrium has been evaluated prospective in 140 patients in regards to grade, depth of myometrial invasion, uterine size, pelvic and paraaortic lymph node metastasis. Metastasis to the lymph nodes appears to correlate well with other important prognostic factors. When additional cases are added and the total data base further analyzed, we hope to develop treatment protocols that will test optimal individualized management.

Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: A Gynecologic Oncology Group study

The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiation therapy for endometrial carcinoma in a randomized, prospective manner. The study population consisted of patients clinically stage I or II (occult) who, after surgical-pathologic evaluation, had one or more risk factors for recurrence: greater than 50% myometrial invasion, pelvic or aortic node metastasis, cervical involvement, or adnexal metastases. All patients without aortic node metastasis received 5000 rads to the whole pelvis at 160-180 rads per day. If aortic node metastasis was documented, aortic field radiation to the top of T12 was offered. The aortic target dose was 4500 rads at 150 rads per day. After completion of radiation therapy, the patients were randomized to receive doxorubicin bolus therapy (60 mg/m2 starting dose) to a maximum cumulative dose of 500 mg/m2. Between November 1977 and July 1986, 92 patients were entered into the doxorubicin (DOX) treatment arm, and 89 patients entered the no-DOX arm. There was no statistically significant difference in survival or progression-free interval of the two arms. The 5-year survival rates for patients with deep myometrial invasion, cervical involvement, and pelvic node metastases were similar (63-70%), whereas the rate for patients with aortic node metastases was 26%. There was no significant difference in the recurrence pattern between the two treatment arms. There were no cases of grade 3 or 4 cardiac toxicity. Twelve patients (6.9%) developed small bowel obstruction after radiation therapy. There were three treatment-related deaths in the DOX arm and two in the radiation therapy-only arm. We conclude that, because of protocol violations, small sample size, and the number of patients lost to follow-up, this study was unable to determine what effect use of doxorubicin as adjuvant therapy had on recurrence, progression, and survival of the endometrial cancer study population. The combination of surgical staging and postoperative radiation as used in this study appears to increase the risk of bowel complications.

The utility of the revised International Federation of Gynecology and Obstetrics histologic grading of endometrial adenocarcinoma using a defined nuclear grading system. A gynecologic oncology group study

Background. The histologic grade of endometrial adenocarcinoma is related to the aggressiveness of the tumor and probability of death from disease. However, the ideal system for assignment of histologic grade remains controversial. In 1988, the International Federation of Gynecology and Obstetrics (FIGO) revised its recommendations for grading typical endometrial adenocarcinoma, such that grade is determined primarily by the architecture of the tumor and secondarily modified in the presence of “notable nuclear atypia”; this phrase, however, has never been defined, and therefore the prognostic validity of this system is unknown.

Cold-knife conization versus conization by the loop electrosurgical excision procedure: A randomized, prospective study

Abstract Objective: Our purpose was to compare the diagnostic ability and treatment efficacy of conization by the loop electrosurgical excision procedure with cold-knife conization. Study Design: One hundred eighty women who required conization for diagnosis and treatment of cervical dysplasia or microinvasive cervical carcinoma were prospectively enrolled in a randomized clinical trial to receive either cold-knife conization or conization by the loop electrosurgical excision procedure. Conization complications, rate of lesion clearance, and therapeutic outcome were assessed for the 2 study groups. Results: There were no statistically significant differences in the complication rate ( P = 1.00), the rate of lesion clearance ( P = .18), or the rate of disease recurrence ( P = .13) between the 2 study groups. The mean follow-up was 11.2 months in the cold-knife conization group and 10.4 months in the loop-excision conization group. Conclusion: Cold-knife conization and loop-excision conization yield similar diagnostic and therapeutic results. (Am J Obstet Gynecol 1999;180:276-82.)

Pelvic exenteration: Ten-year experience at the European Institute of Oncology in Milan

OBJECTIVES Analyze morbidity and survival after pelvic exenteration (PE) of gynecological malignancies. METHODS We reviewed 106 consecutive patients with gynecologic malignancies who underwent PE from June 1996 to April 2007 at the Division of Gynecology, European Institute of Oncology (IEO), Milan. RESULTS PE was performed for cancer of the cervix (62 patients), vagina (21 patients), vulva (9 patients), endometrium (9 patients), ovary (4 patients) and 1 uterine sarcoma. Mean age was 53.6 (30-78) years. 97% of the patients received radiotherapy before PE and 3 patients had PE as primary treatment. We performed 53 anterior, 48 total and 5 posterior PE. Median operation time, estimated blood loss and hospital stay were respectively 490 (200-780) minutes, 1240 (300-6500) ml and 21.6 (11-55) days. No residual tumor was left in 93% of the patients. Median follow-up was 22.3 (1.6-117) months. There were no post-operative deaths (<30 days from surgery) nor intra-operative mortality. Total morbidity rate was 66%; 48% of patients had early complications (<30 days after PE) whereas 52 patients (48.5%) had late complications; 70% of these occurred to the urinary tract and 25% were due to bowel occlusions or fistulas. Overall survival was 52%, 35%, 19% and 16% respectively for cervical, endometrial, vaginal and vulvar cancer. CONCLUSIONS PE is a feasible technique with no post-operative mortality and high percentage of long-survivors, although the morbidity rate still remains significantly high. Careful patient selection, pre- and post-operative care and optimal surgical skills in a Gynecologic Oncologic Center are the cornerstones to further improve quality of life and survival for these patients.