Vulvar melanoma at the M. D. Anderson Cancer Center: 25 years later.

The purpose of this study was to review the clinical course of patients diagnosed with vulvar melanoma. Charts of patients diagnosed between 1970 and 1997 were reviewed for demographics, lesion characteristics, disease duration and extent, and treatments. Actuarial survival curves were computed by the Kaplan Meier method and compared by Cox proportional hazards regressions. Fifty-one patients (median age 54) with vulvar melanoma presented with a vulvar mass (39%), pain (30%), bleeding (24%), and itching (20%). Anatomical distribution was mucosa of the vulva (65%), vulvar epidermal site (21%), or unspecified vulva (14%), with 20% having multifocal disease at diagnosis. Histologic types were superficial spreading or nodular (50% each). Median lesion characteristics were diameter 2 cm, Breslow index 4.4 mm, and Clark level IV. Distribution of patients per American Joint Committee on Cancer (AJCC) stage was 29%, 50%, 16%, and 7% for stages I, II, III and IV, respectively. Inguinal node metastases were unilateral in 16% and bilateral in 7%. Despite complete surgical resection, 32 patients (63%) recurred. Median survival for all patients was 41 months (range, 5-324), with 91% 5-year survival for patients with stage I and 31% for stage >or= IIA (P = 0.0002). As with cutaneous melanoma, the AJCC classification, Breslow's thickness, and Clark's levels are the major predictors of overall survival (P = 0.0001 each) and disease-free survival (P

Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.

BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.

Intraoperative lymphatic mapping and sentinel node identification with blue dye in patients with vulvar cancer.

OBJECTIVE: To determine the effectiveness of intraoperative lymphatic with blue dye alone as a means of localizing sentinel nodes in patients with vulvar cancer. METHODS: All patients undergoing primary surgical treatment for vulvar cancer were eligible for this prospective study. Isosulfan blue dye was injected intradermally at the edge of the primary tumor closest to the adjacent groin. Bilateral dye injections and groin dissections were performed if the tumor was within 2 cm of the midline. RESULTS: Fifty-two patients were enrolled in the study between 1993 and 1999. The median age was 58 years. Eighty-seven percent of the patients had T1 or T2 lesions, and 92% had nonsuspicious lymph nodes on palpation. Sixty-seven percent of the patients had squamous cell carcinoma; the remaining patients had melanoma or adenocarcinoma. The sentinel node was identified in 46 of the 52 patients (88%), comprising 22 of the 25 patients with lateral tumors and 24 of the 27 patients with midline lesions. The sentinel node was successfully identified in 57 of the 76 (75%) dissected groins. Sentinel node identification in the groin was hampered by the effects of prior excisional biopsy vs punch biopsy (11 of 25 vs 8 of 51, P = 0.007) and by the lateral vs midline location of the tumor (22 of 25 groins vs 35 of 51 groins, P = 0.067). During the first 2 years (1993-1994), a sentinel node could not be identified in 4 of the 25 (16%) patients and 13 of the 36 (36%) groins dissected, compared with 2 of the 27 (7%) of patients treated and 6 of the 40 (15%) groins dissected from 1995 through 1999 (P = 0.034). A total of 556 nodes were removed (median, 7 per groin), of which 83 (median, 1 per groin) were sentinel. The sentinel node was not identified in 2 of the 12 groins that proved to have metastatic disease. Both events occurred in the first 2 years of the study. There were no false-negative sentinel nodes. Since 1995, we have successfully identified the sentinel node in 16 of the 16 patients (25 of 25 groins) with T1 or T2 primary lesions, squamous histology, and nonsuspicious groin nodes on physical examination. CONCLUSIONS: Experience and careful patient selection can permit sentinel node identification with blue dye injection alone in more than 95% of patients with vulvar cancer.

High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer.

OBJECTIVE: The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer. METHODS: Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0. RESULTS: The optimal topotecan dose selected for future trials was 4.0 mg/m(2)/day x 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive. CONCLUSION: With a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer.

Hypersensitivity reactions and the utility of oral and intravenous desensitization in patients with gynecologic malignancies.

OBJECTIVES: The aims of this study were to characterize hypersensitivity reactions to chemotherapy in patients with gynecologic malignancies and to determine the utility of oral and intravenous desensitization. METHODS: We retrospectively reviewed patients with hypersensitivity reactions identified by direct physician query and by review of charts with ICD9 code E933.1 (Adverse Effect Anti-Neoplastic). RESULTS: Thirty-two patients were identified: 27 with ovarian cancer, 4 with primary peritoneal cancer, and 1 with cervical cancer. Nine patients experienced hypersensitivity reactions during the primary regimen and 23 during chemotherapy for recurrent disease. Hypersensitivity occurred following an average of nine courses. Hypersensitivity occurred secondary to paclitaxel (10) carboplatin (16), cisplatin (4), bleomycin (1), and paclitaxel/carboplatin combination therapy (1). Patients had previously received the agent in 93.8% of carboplatin reactions, in 54.5% of paclitaxel reactions, and in all other agent reactions. Hypersensitivity reactions most commonly included flushing, dyspnea/bronchospasm, back pain, chest discomfort, pruritus, erythema, and nausea and occasionally included alterations in blood pressure or pulse rate. Reactions were successfully treated in 96.9% of patients by interrupting the infusion and administering steroids, antihistamines, benzodiazepines, nebulized beta-agonists, and/or pressors. Seventeen patients underwent desensitization, one to two agents, with 94% success. Nine of ten patients had successful iv desensitization, and 8/10 patients had successful oral desensitization. One failure on the oral regimen had previous successful iv desensitization. CONCLUSIONS: Hypersensitivity reactions to chemotherapeutic agents do not necessarily require exclusion of a compound from the treatment regimen. Intravenous and oral desensitization protocols are useful for successful and safe administration of paclitaxel and platinum compounds in patients with prior hypersensitivity reactions.

Treatment of uterine papillary serous carcinoma with paclitaxel.

OBJECTIVE: The aim of this study was to determine the effectiveness and toxicity of monthly treatment with intravenous paclitaxel for women with advanced or recurrent uterine papillary serous carcinoma (UPSC). METHODS: Consenting women with histologically confirmed advanced (FIGO stage III or IV) or recurrent UPSC were treated on an Institutional Review Board approved protocol of a 24-h intravenous infusion of 200 mg/m(2) of paclitaxel every 3 weeks. Both measurable and nonmeasurable disease cases were enrolled. Treatment was continued until disease progression, patient intolerance, or (in women with nonmeasurable disease) completion of six courses. RESULTS: Twenty patients received from 1 to 11 cycles of therapy. Two women died of disease after 1 cycle of therapy and were not evaluable for response. Among 13 women with measurable tumor receiving 2 or more cycles of therapy, 4 had a complete clinical response and 6 had a partial response (objective response rate, 77%). The median time to progression was 7.3 months (range, 2-21 months). All 3 remaining patients with measurable disease had stable disease for a median of 6 months. The 5 patients without evaluable disease received 5 to 6 cycles of adjuvant paclitaxel. Three developed recurrence (range, 4-10 months; median, 7.2 months). Neutropenia was the major toxicity. Eleven of the 20 patients required G-CSF support, and 9 were hospitalized for neutropenic fever. One woman had reversible cardiac symptoms, which might have been related to paclitaxel treatment. At the time of analysis (mean follow-up, 23 months; range, 4.3-59.9 months), 13 women had died of disease, 4 were alive with disease, and 2 were disease free. All 3 disease-free patients had been treated for nonmeasurable advanced stage disease. CONCLUSION: Paclitaxel appears to have excellent activity in the treatment of advanced or recurrent UPSC, an uncommon but aggressive malignancy. Longer survival appears to be more common among women with small-volume disease.

In vitro and in vivo adenovirus-mediated p53 and p16 tumor suppressor therapy in ovarian cancer.

PURPOSE: The objectives of this study were to determine the effects of adenovirus-mediated p16 and p53 on growth and apoptosis in ovarian cancer cells and on survival in nude mice implanted with human ovarian cancer cells. EXPERIMENTAL DESIGN: SKOV-3 ip1 (p53 and p16 null), 2774 (p53 and p16 mutant), and OVCA 420 (p53 and p16 wild-type) cells were used for in vitro studies. SKOV-3 ip1, 2774, and Hey A8 (p53 and p16 wild-type) cells were used in the nude mouse studies. The E1-deleted adenoviruses containing p53, p16, or beta-galactosidase cDNA were transfected into the different cell types or inoculated into the nude mice after injection with ovarian cancer cells. RESULTS: Cell counting, microtetrazolium, and anchorage-independent growth assays on transfected cells demonstrated that p16 and the p16/p53 combination suppressed growth, whereas p53 did not (except in the anchorage-independent growth assay). Although cells infected with the p16/p53 combination had decreased growth compared with cells infected with either tumor suppressor alone, the difference was only statistically significant compared with p53. p16, p53, and the p16/p53 combination all increased apoptosis in the cells. In the nude mice, p16 treatment resulted in the longest survival for all three models, although it only reached statistical significance for the 2774 and SKOV-3 ip1 groups. CONCLUSIONS: Overall, p16 demonstrated greater growth inhibition than p53 both in vivo and in vitro. The p16/p53 combination demonstrated a consistent trend toward increased growth suppression and apoptosis over p16 or p53 alone. Adenovirus-mediated p16 may be a viable future treatment for ovarian cancer.

Secondary cytoreductive surgery for localized intra-abdominal recurrences in epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to evaluate the role of secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer with an apparent solitary intra-abdominal focus. METHODS: We conducted a retrospective review of patients with epithelial ovarian cancer who underwent secondary cytoreduction for recurrence at the University of Texas M. D. Anderson Cancer Center between 1985 and 1994. Eligible patients included those who had a laparotomy to resect a tumor that was apparently solitary. Cytoreductive surgery was defined as optimal if the diameter of the largest residual tumor was < or =2 cm and suboptimal if >2 cm. RESULTS: Twenty-five patients met our eligibility criteria. Their mean age was 55 years (range, 35-73 years). The median time from primary diagnosis to recurrence was 37.6 months. Tumor was found to be confined to a solitary site in 15 patients (60%), to two sites in 6 (24%), and to three or more sites in 4 (16%). Surgical procedures included cytoreduction in 10 patients, intestinal resection in 8, splenectomy in 3, and limited biopsies in 4. Secondary cytoreduction was optimal in 18 of 25 patients (72%). The median postsecondary cytoreduction survival was 25.1 months for patients who had suboptimal secondary cytoreduction compared with 56.9 months for those who had optimal cytoreduction (P = 0.08). CONCLUSIONS: Secondary cytoreductive surgery for recurrent ovarian cancer at an apparently solitary intra-abdominal site resulted in optimal residual tumor in a high proportion of patients. Although there was no survival advantage for patients whose tumor was optimally debulked, there was a trend toward improved survival. A large prospective randomized trial of secondary cytoreduction for recurrence is recommended.

Reliability and validity of the functional assessment of cancer therapy-ovarian.

PURPOSE: To report the reliability and validity of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) in a consecutive series of outpatients with epithelial ovarian cancer. PATIENTS AND METHODS: Two hundred thirty-two ovarian cancer patients attending an outpatient gynecologic oncology clinic completed questionnaires at baseline. The patients' FACT-O scores were compared with their performance status, disease stage, treatment status, and other factors hypothesized to be related to quality of life. Patients received a second questionnaire either one week after baseline to assess the instrument's test-retest reliability and/or two months after baseline to evaluate its sensitivity to change in performance status. RESULTS: Internal consistency and test-retest reliability of the FACT-O were adequate. Overall, the scales correlated with other measures as expected; all correlations were in the hypothesized direction. Patients with advanced disease, poor performance status, and who were receiving active treatment had lower scores on physical, functional, and ovarian cancer-specific scales. The total FACT-O and emotional well-being scores were lower for patients with poor performance status and patients in active treatment. The FACT-O total and all subscale scores except emotional well-being were sensitive to decreases in performance status. CONCLUSION: Overall, the FACT-O provides a reliable and valid assessment of the quality of life of women with ovarian cancer, and is appropriate as a brief quality of life assessment in clinical trials and descriptive studies.

Survey of female gynecologic oncologists and fellows: balancing professional and personal life.

OBJECTIVE: The aim of this study was to determine how female gynecologic oncologists have dealt with the challenge of combining childbearing and a career in gynecologic oncology and to identify other issues which need to be addressed to improve job satisfaction. METHODS: This survey of female members of the Society of Gynecologic Oncologists and fellows addressed demographics, timing of childbearing, type and cost of childcare, satisfaction with childcare choices, and mentorship. Those without children were queried about plans and reservations. Open-ended questions investigated how female gynecologic oncologists felt job satisfaction could be improved. RESULTS: A total of 65/110 (59%) attendings and 18/36 (50%) fellows responded. Three-fourths of respondents felt that the ideal time to have children was postfellowship. Timing of childbearing caused moderate to severe stress in the personal relationships of 23% of respondents. Median maternity leave was 6 weeks (1-120 days). Seventy-eight percent of female gynecologic oncologists with children employed a nanny. Over half of the respondents estimated weekly childcare cost at over $400. A successful balance between family and full-time practice was the most commonly cited quality of an ideal mentor. Sixty-six percent of the respondents replied to open-ended questions with narrative answers, revealing three major areas for improvement: childcare issues, increased flexibility in hours and duties (clinical, surgical, and research), and the need for more female mentoring. CONCLUSIONS: This survey highlighted the concerns of female gynecologic oncologists about achieving a successful balance between family and professional duties. It also revealed the ways in which women have responded and identified other issues that may be targeted to improve job satisfaction.

Depression, anxiety, and quality of life in patients with epithelial ovarian cancer.

OBJECTIVE: The aims of this study were to evaluate psychological distress and quality of life (QOL) in patients with epithelial ovarian cancer (EOC) and to examine the relationship between these problems and health and demographic variables. METHODS: Of 344 consecutive patients identified, 246 completed questionnaires. Four dimensions of QOL were assessed including physical, functional, emotional, and social/family well-being, as well as concerns specific to ovarian cancer patients. Depression was measured with the Center for Epidemiologic Studies-Depression (CES-D) scale and anxiety was measured by the State Anxiety Subscale of the Spielberger State-Trait Anxiety Inventory. Performance status was evaluated by the Zubrod score. RESULTS: Sixty-five patients (26%) had early stage disease; 181 (74%) had advanced disease. One hundred twenty-one patients (49%) were under active treatment, while 124 (51%) were seen for posttherapy surveillance. Forty-eight (21%) met CES-D cutoff criteria for a clinical evaluation for depression, and 29% scored above the 75th percentile for anxiety. Performance status was related to depression, anxiety, and QOL problems, except in the domain of social well-being. CONCLUSIONS: Clinically significant depression and anxiety may be more prevalent in patients with EOC than previously reported. Future studies of screening for and treating psychological distress are being designed to improve QOL in these women.

Pharmacoeconomic considerations in treating ovarian cancer.

Ovarian cancer is the leading cause of death in women with gynaecological cancers. The most common type of ovarian cancer is epithelial ovarian cancer. Referred to as the 'silent' killer, this disease is difficult to detect because of the lack of specific symptoms. The majority of women who have ovarian cancer are diagnosed in the advanced stages. While the exact cause of ovarian cancer remains elusive, it is believed that the events relating to incessant ovulatory function play a major role in the development of this disease. Long term prognosis of women with ovarian cancer remains grim. Although ovarian cancer is highly responsive to chemotherapy, most women will develop persistent or recurrent disease after primary treatment. The standard front-line treatment is paclitaxel in combination with a platinum-based agent; however, toxicities associated with paclitaxel must be weighed against the clinical benefit. The economic issues associated with the treatment of ovarian cancer involve costs of chemotherapy agents and management of supportive care. Patient preferences and quality-of-life issues are also of major importance because of the short survival benefit for most patients. Therefore, quality of life must be maximised alongside efforts to prolong survival. More research is necessary to determine what trade-offs (e.g. adverse effects of treatment) patients are willing to make for modest gains in survival.

Intensive-dose ifosfamide and etoposide with filgrastim for cytoreduction before peripheral blood stem cell collection in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the antitumor activity and toxic effects of intensive-dose ifosfamide plus etoposide with filgrastim given as stem cell mobilization therapy before high-dose chemotherapy for recurrent or persistent ovarian cancer. METHODS: We studied 32 patients with epithelial ovarian cancer who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 (total dose) by continuous infusion over 72 h; etoposide was given at 150 mg/m2 in 2-h infusions every 12 h during the same 72-h period; and filgrastim was given at 10 microg/kg/day subcutaneous injection from day 5 through completion of stem cell harvest. RESULTS: Nine (64%) of the 14 patients assessed responded to the treatment. The target stem cell dose was achieved with a median of 1 apheresis (range 1-5 aphereses). Nonhematologic toxicity was limited to grade 2 nephrotoxicity in one patient and grade 2 hepatic toxicity in three patients. CONCLUSIONS: In this patient group, intensive-dose ifosfamide plus etoposide with filgrastim was well tolerated and produced antitumor activity.

Posttherapy surveillance of women with cervical cancer: an outcomes analysis.

OBJECTIVE: The aim of this study was to develop a surveillance program that optimizes clinical outcome following primary treatment of women with cervical cancer. METHODS: The records of 1096 patients with FIGO stage IB cervical cancer treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed by site, presence or absence of symptoms, method of detection, and survival. Univariate and multivariate analyses using a Cox proportional hazards model were performed. RESULTS: One hundred thirty-three patients (13%) developed recurrent disease. Of these, 114 were symptomatic and 19 were asymptomatic at the time of recurrence. Thirty-seven patients recurred in the central pelvis, 21 each in the lung or pelvic wall, 22 in nodes, and 35 in other sites. The median disease-free interval was 17 months for symptomatic patients and 16 months for asymptomatic patients. The median survival from initial diagnosis was 31 months for symptomatic and 83 months for asymptomatic patients (P = 0.001). The median survival from recurrence was 11 months for symptomatic and 42 months for asymptomatic patients (P < 0.001). Multivariate analysis revealed that symptom status at time of recurrence was a significant predictor of survival, even when known prognostic factors were considered (P < 0.001). All asymptomatic pelvic recurrences were diagnosed by pelvic exam; all asymptomatic pulmonary recurrences were detected by chest radiographs. Pap smears did not detect a single asymptomatic recurrence. CONCLUSIONS: Posttherapy surveillance programs are directed toward asymptomatic patients in whom early detection of recurrence may impact survival. These data indicate that a subset of women may benefit from surveillance. A model for surveillance is proposed.

Cavitational ultrasonic surgical aspiration for the treatment of vaginal intraepithelial neoplasia.

OBJECTIVE: The aim of this study is to determine whether cavitational ultrasonic surgical aspiration (CUSA) is effective and safe for treating vaginal intraepithelial neoplasia (VAIN). METHODS: We conducted a retrospective chart review of 46 patients who were treated with CUSA for VAIN in a single gynecologic oncology practice between 1981 and 1999. RESULTS: At initial presentation, 39% of treated patients had grade I VAIN, 20% had grade II, and 41% had grade III. The mean duration of follow-up from initial CUSA treatment was 21 months. Twenty-nine patients (63%) were initially treated with CUSA, 7 patients (15%) with laser vaporization, 7 patients (15%) with surveillance by Papanicolaou smear, 1 patient (2%) with partial vaginectomy, 1 patient (2%) with 5-fluorouracil, and 1 patient (2%) with loop excision. Patients initially treated with CUSA had a higher percentage of grade III VAIN at diagnosis (48%) than did patients initially treated with other methods (29%). A significantly greater proportion of patients initially treated with CUSA had no recurrence of VAIN (66%) compared with patients initially treated with other methods (0%) (P < 0.0001). A significantly greater proportion of patients who were treated for recurrent disease with CUSA had no further recurrence (52%) compared with patients treated for recurrent disease with other methods (9%) (P < 0.001). No patient treated with CUSA reported adverse effects; 7 patients treated with other methods reported dysuria, burning, and pain. CONCLUSION: These initial data suggest that CUSA is a safe and effective method for treating VAIN and may be an appropriate treatment for many patients.

High-dose ifosfamide and etoposide with filgrastim for stem cell mobilization in patients with advanced ovarian cancer.

High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation has shown promise as treatment for recurrent or persistent epithelial ovarian cancer. We evaluated the stem cell mobilization regimen of high-dose ifosfamide plus etoposide in 32 patients with epithelial ovarian cancer, who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 by continuous i.v. from days 1 to 3. Etoposide was given at 150 mg/m2 every 12 h for six doses on days 1-3. Filgrastim was given at 10 microg/kg/d s.c. from day 5 until the completion of peripheral blood stem cell harvest. Fourteen of 32 patients had measurable or evaluable disease before mobilization therapy and were assessed for response. In nine (64%) of the 14 patients, treatment response was demonstrated, and these patients received a second cycle of mobilization therapy. The target CD34+ cell dose (>8 x 106 cells/kg) was achieved with a median of one apheresis (range 1-5). A median of 25.1 (range 8.0-122.5) x 106 CD34+ cells/kg body weight was collected. Non-hematologic toxicity was limited to grade 2 renal dysfunction in one patient and grade 2 hepatic dysfunction in three patients. In this patient group, high-dose ifosfamide plus etoposide with filgrastim support was well tolerated, lead to successful stem cell harvest and had antitumor activity.

Paget's disease of the vulva: pathology, pattern of involvement, and prognosis.

OBJECTIVE: The aim of this study was to determine prognostic factors and risk factors for recurrence in patients with Paget's disease of the vulva. METHODS: The medical records of 76 patients with a diagnosis of Paget's disease of the vulva were retrospectively reviewed. The diagnosis in each case was confirmed by reviewing the pathology. Patients were then divided into four groups by diagnosis: intraepithelial Paget's disease (IEP) (n = 46), invasive Paget's disease (IP) (n = 9), intraepithelial Paget's disease with underlying adenocarcinoma (IEPUA) (n = 13), and intraepithelial Paget's disease with a coexisting cancer (CCA) (n = 8). Comorbid conditions, location of disease, pathologic diagnosis, method of treatment, margin status, and current status of the patient were evaluated. Descriptive statistical data and univariate analysis were generated using the Statview statistical package. RESULTS: A diagnosis of IEPUA, IP, or CCA predicted a poor survival (P = 0. 0017). Patients who had received chemotherapy or radiation as treatment had a poor survival (P < 0.0001 and 0.0002). Patients with clitoral Paget's disease had a higher incidence of death from disease (P = 0.026). When death from all causes was considered, patients treated with wide local excision (WLE) had a significantly longer survival than patients treated with other more radical treatments (P = 0.02). Risk factors for recurrence included treatment with WLE (P = 0.004). CONCLUSIONS: Patients with IP, IEPUA, or CCA have a poorer prognosis than patients with IEP. Location of Paget's disease is important for prognosis; and patients with clitoral Paget's disease may require more aggressive treatment. WLE is associated with a higher risk of recurrence, but overall patients with WLE tend to survive longer than patients treated more radically.