J.T. Wharton

Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer

A retrospective matched-control study was conducted to review our experience with FIGO stage III and IV epithelial ovarian cancer in patients referred after initial laparotomy and biopsy only. The study group comprised 22 patients; planned treatment was two to four cycles of chemotherapy, interval debulking surgery, six more chemotherapy cycles, and second-look laparotomy. Two control groups were matched with the study group according to FIGO stage, histologic type, and grade (2 or 3) and patient age +/- 5 years. The first control group (22 patients) had greater than 2 cm residual disease after initial surgery; their planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. The second control group (18 patients) was referred after initial laparotomy and biopsy only; their disease was immediately reexplored and debulked. Subsequent planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. All patients received cisplatin-based chemotherapy. Optimal cytoreduction to less than or equal to 2 cm was achieved for 77% of the study group vs 39% of the immediate-reexploration group (P = 0.02). Median survival times for the three groups were not different (16 vs 19.3 vs 18 months, respectively) (P = 0.58). Within the study group, patients who were optimally debulked survived significantly longer than those who were not (18.1 vs 7.5 months) (P = 0.02). Morbidity of the interval debulking procedure was acceptable. Study findings suggest that patients with bulky residual disease have a uniformly poor prognosis regardless of the timing of further surgery.

Adjuvant chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC) for early-stage high-risk endometrial cancer: A preliminary analysis☆

Abstract Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors with middle- or outer-third myometrial invasion (16), grade 3 tumors with any degree of myometrial invasion (17), presence of extrauterine disease with no gross residual (17), or a high-risk histologic subtype including papillary serous (4), adenosquamous (5), or clear cell (1) tumors. Patients received PAC (50/50/500 mg/m 2 ) at 4-week intervals for six cycles. Thirty patients (90%) completed therapy. Toxicity included severe neutropenia in 14 patients, neutropenic sepsis in 2 patients, and doxorubicin-related cardiomyopathy in 1 patient. There were no treatment deaths. Current median follow-up is 25 months. Nine patients (27%) have developed a recurrence, 7 of whom died, after a median interval of 14 months. Eight of the 9 with recurrence initially had extrauterine disease ( P = 0.02). The resulting 2-year actuarial progression-free and overall survival rates were 79 and 83%, respectively. The median progression-free interval was 29 months for patients with extrauterine disease and 45 + months for those with no extrauterine disease ( P = 0.02). These results suggest that a phase 3 randomized trial comparing adjuvant PAC with radiation therapy is warranted.

Pelvic exenteration in the elderly patient

Advanced age is frequently considered a contraindication to radical exenterative surgery. We reviewed the outcomes of 63 patients age 65 years or older who underwent pelvic exenteration between 1960-1991 at The University of Texas M. D. Anderson Cancer Center. Sixty-three percent had preexisting medical illnesses. Major or potentially lifethreatening complications were noted in 38% of the patients. An additional 38% experienced minor complications. Sixty percent experienced one or more infectious complications, including pyelonephritis, wound infection, sepsis, and flap necrosis. When both major and minor complications were considered, infectious morbidity was the single largest category. Although they are riot life-threatening, nonspecific infectious morbidity and transient confusion were the most frequent individual complications, occurring in 26 and 24% of patients, respectively. Twenty-four percent of the patients experienced no complications. Thirty-four percent of the postoperative survivors suffered late major morbidity. Operative mortality was 11%; multisystem failure was the most frequent cause of death. After a mean follow-up of 4 years, 22 patients were alive with no clinical evidence of disease. Twenty-one patients died of recurrent disease, with a median time to recurrence of 9.6 months. The 5-year survival rate for the group was 46%. In comparison, 363 patients younger than age 65 who underwent exenteration during the same period experienced an operative mortality rate of 8.5% and a 5-year survival rate of 45%, neither of which were significantly different from the rates found for the older group (P=.51 and .52, respectively). The morbidity and mortality of pelvic exenteration in our elderly patients are comparable to those noted in previous studies of younger patients, with similar 5-year survival rates. Therefore, age should not be considered a contraindication to exenteration.

Prognostic factors in stage IB squamous cervical cancer patients with low risk for recurrence

About one-half of cervical cancer patients whose tumors recur after radical surgery have negative lymph nodes and clear resection margins. We evaluated 95 patients with squamous cell tumors who underwent radical hysterectomy and pelvic lymphadenectomy between January 1975 and December 1985 and who were thought to be at low risk for recurrence to see whether other clinical or histopathologic factors were predictive of tumor recurrence. Detailed retrospective record review and complete pathology review were accomplished for each case. The 5-year actuarial survival rate was 89%. Nine patients developed recurrent disease (9.5%), of whom eight died. Several clinical features were evaluated as possible prognostic factors: patient age (P=.26), patient race (P=.60), cervical diameter (P=.24), extent of gross cervical involvement (P=.36), and presence of contact bleeding (P=.82). Histopathologic features were examined: depth of invasion (P=.31), number of mitoses (P=.42), character of the tumor-stromal border (P=.15), histologic differentiation (P=.02), lymph-vascular space invasion (P=.56), and width of tumor (P=.23). Depth of invasion did correlate with increasing tumor width (P<.001). Once node- and margin-positive patients are excluded, differentiation may be the only feature useful in identifying patients at risk for recurrence. Because almost one-half of our patients had poorly differentiated tumors, sole use of this feature as a criterion for adjuvant therapy would have resulted in overtreatment of low-risk patients.

Radical wide excision and selective inguinal node dissection for squamous cell carcinoma of the vulva

Limited resection of some vulvar cancers may provide cure rates equivalent to those obtained with radical vulvectomy and bilateral inguinal node dissection. Rapid recovery, fewer complications, and better functional result have been described as advantages to less extensive procedures. Since 1978, 32 patients with invasive squamous cell cancer of the vulva (depth greater than 1 mm) and clinically negative inguinal lymph nodes underwent radical wide excisions as primary therapy. Mean age at diagnosis was 61 years. Seventeen patients had T1 and 15 had T2 tumors. Resection of the primary lesion was tailored to lesion location and size, and dissection was carried to the deep perineal fascia. Twenty-two patients had unilateral superficial inguinal lymph node dissections, five with midline lesions had bilateral superficial dissections, and five had node samplings which included deep inguinal nodes. Depth of invasion ranged from 1.5 to 13.0 mm. Mean largest lesion dimension was 23 mm. Five-year lifetable survival for the entire group was 84%. Univariate analysis of potential prognostic variables showed no significant recurrence or survival differences for patient age (P = 0.56), symptom duration (P = 0.57), FIGO stage (P = 0.67), tumor grade (P = 0.20), tumor location (P = 0.26), depth of invasion (P = 0.56), or resection margin status (P = 0.63). Thirty-one percent of patients had perioperative complications, and 16% developed delayed complications. Mean hospital stay was 10 days. Three patients (10%) developed new or recurrent vulvar disease and underwent additional therapy. None have died of disease, although one is alive with persistent tumor. Radical wide excision and selective inguinal lymphadenectomy constitute a reasonable alternative to radical vulvectomy with bilateral inguinal node dissections for squamous tumors clinically limited to the vulva. Outcome may not be strongly influenced by lesion size or depth of invasion.

Endometrioid carcinoma of the ovary: Retrospective review of 145 cases

From 1967 through December 1987, 145 patients with endometrioid carcinoma of the ovary were treated at the University of Texas M. D. Anderson Cancer Center. Thirty-eight patients (26.2%) had stage I disease, 28 (19.3%) stage II, 60 (41.4%) stage III, and 11 (7.6%) stage IV; 8 patients (5.5%) were unstaged. Grade 2 or 3 histology was seen in 119 patients (82.1%). In addition to surgical therapy, 128 patients underwent chemotherapy, including single-agent therapy, noncisplatin combination therapy, and cisplatin-based therapy. No statistically significant improvement in median survival was noted among these three chemotherapy groups for stages II, III, and IV (P = 0.22). A significant improvement in median survival was noted for those patients who achieved a complete clinical response, regardless of type of chemotherapy (96 or more months for single-agent therapy, P = 0.001; 31.5 months for noncisplatin combination therapy, P = 0.016; and 85 months for cisplatin-based therapy, P = 0.0001). Synchronous ovarian and uterine malignancies were seen in 18 patients (12.4%). No difference in survival was seen for patients with endometriosis (P = 0.13) or endometrial cancer (P = 0.09) when compared with those who did not have these histologic findings.

Secondary cytoreductive surgery in epithelial ovarian cancer: Nonresponders to first‐line therapy

ate differentiation. Intraoperative studies demonstrated that the tumor secreted testosterone, androstenedione, 17 alphahydroxyprogesterone, and estradiol, but not dehydroepiandrosterone sulfate. These findings support the thesis that hormonal manipulation tests cannot differentiate between adrenal and ovarian virilizing tumors. Nor does the oral contraceptive suppression of testosterone secretion exclude an ovarian malignancy. The patient remains free of recurrence after 7 years.

Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC)

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.

Adjuvant chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC) for early-stage high-risk endometrial cancer: A preliminary analysis

Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors with middle- or outer-third myometrial invasion (16), grade 3 tumors with any degree of myometrial invasion (17), presence of extrauterine disease with no gross residual (17), or a high-risk histologic subtype including papillary serous (4), adenosquamous (5), or clear cell (1) tumors. Patients received PAC (50/50/500 mg/m2) at 4-week intervals for six cycles. Thirty patients (90%) completed therapy. Toxicity included severe neutropenia in 14 patients, neutropenic sepsis in 2 patients, and doxorubicin-related cardiomyopathy in 1 patient. There were no treatment deaths. Current median follow-up is 25 months. Nine patients (27%) have developed a recurrence, 7 of whom died, after a median interval of 14 months. Eight of the 9 with recurrence initially had extrauterine disease (P = 0.02). The resulting 2-year actuarial progression-free and overall survival rates were 79 and 83%, respectively. The median progression-free interval was 29 months for patients with extrauterine disease and 45+ months for those with no extrauterine disease (P = 0.02). These results suggest that a phase 3 randomized trial comparing adjuvant PAC with radiation therapy is warranted.

Transitional cell carcinoma of the ovary: A matched control study of advanced‐stage patients treated with cisplatin‐based chemotherapy

OBJECTIVE: The purpose of this study was to compare patients with advanced-stage transitional cell carcinoma of the ovary with those who had poorly differentiated serous carcinoma for surgical response and survival. STUDY DESIGN: Sixty-two patients with transitional cell carcinoma were identified through a retrospective review and were matched with serous carcinoma patients for stage and residual disease. All patients received cisplatin-based chemotherapy. End points selected for analysis were surgical response, progression-free survival time, and survival time. Univariate and multivariate regression analyses were also performed. RESULTS: The surgical complete response rate for patients with transitional cell carcinoma was 37%, compared with 11 % for those with serous carcinoma (p < 0.001). The survival time was significantly longer for the patients with transitional cell carcinoma (median 52.3 vs 22.0 months) (p < 0.001). Multivariate analyses strengthened these findings. CONCLUSION: Transitional cell carcinoma of the ovary is significantly more chemosensitive and associated with a better prognosis than the more common serous carcinoma. (AM J OesTET GVNECOL 1993;168:1178-87.)