Gary C. Reid

Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix☆

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P less than 0.0001), and number of nodal metastases (P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter less than 1 cm) and no more than two nodes with metastases fell into the low-risk category; those patients with large cervical lesions (diameter greater than 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.

Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early-stage squamous carcinoma of the cervix with pelvic nodal metastasis: A matched-control study☆

In a retrospective study, 185 patients with previously untreated stage IB or IIA (International Federation of Gynecology and Obstetrics) squamous cell carcinoma of the cervix were found to have pelvic nodal metastasis at the time of Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Of these patients, 103 received adjuvant whole-pelvis irradiation and 82 received no adjuvant therapy. Median dose of pelvic irradiation was 5000 cGy. Among the irradiated patients, in 75% the dose was 5000 cGy or greater. Matching irradiated and nonirradiated patients according to stage, tumor size, and number and location of positive nodes yielded 60 pairs. Mean length of follow-up was 3.9 years for the 60 irradiated patients and 5.8 years for the non-irradiated patients. Kaplan-Meier overall and cancer-specific survival estimates for the two groups were not significantly different (P greater than 0.30). During the follow-up period, 21 surgery-only patients and 22 patients treated with adjuvant radiotherapy had recurrence, but adjuvant radiotherapy decreased the proportion of recurrences occurring in the pelvis alone--27% compared with 67% in the surgery-only group (P = 0.01).

Radical vulvectomy. The decision for the incision

Background. An analysis of survival and complications related to the type of radical vulvectomy operation performed is reported.

Squamous cell carcinoma of the vulva: Prognostic factors influencing survival

One hundred seventy-two cases of patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975 to 1988 are reported. The mean age was 66 years with a range of 21 to 101 years. The distribution by stage included Stage I, 65; Stage II, 44; Stage III, 50; and Stage IV, 13 patients. Groin node dissections performed on 145 patients showed negative nodes, 58%; unilateral positive nodes, 28%; and bilateral positive nodes, 14%. The distribution of patients with positive nodes was influenced by stage: Stage I, 14%; Stage II, 23%; Stage III, 72%; Stage IV, 92%. The overall cumulative 5-year survival was 71% and this was significantly influenced by stage of disease: Stage I, 94%; Stage II, 91%; Stage III, 36%; Stage IV, 26%. Stages I/II and III/IV were combined for analysis. In Stages I/II, survival was significantly influenced by tumor grade while size, patient age, and lymph node status did not influence survival. In Stage III/IV, survival was significantly influenced by tumor size, node status, and number of positive nodes while grade, patient age, and tumor location did not influence survival. Squamous cell cancer of the vulva is effectively treated with radical surgery but advanced-stage disease with regional metastases significantly alters survival.

The management of vaginal melanoma

Between 1964 and 1987 ten patients with vaginal melanoma were treated at the University of Michigan Hospital. Five of the six patients who underwent radical surgery had adequate information concerning the first site of relapse, and in four of these five, pelvic sites or locoregional lymph nodes were the first sites of recurrent disease. One of these patients developed a 17‐cm pelvic recurrence, which responded with a 75% reduction in size 3 months after completion of radiotherapy given in high individual fractions (400 cGy × 11). Three patients were managed with local resection, and all developed recurrent locoregional disease. One patient presented with metastatic disease. We conclude that locoregional control of vaginal melanoma is difficult to achieve with surgery alone. We hypothesize that preoperative radiotherapy to the pelvis (500 cGy × 6 given 3 days a week to the whole pelvis with subsequent consideration for a vaginal boost field) may improve the poor rate of locoregional control of vaginal melanoma that is seen when surgery alone is used.

Continuous infusion of low-dose 5-fluorouracil and radiation therapy for poor-prognosis squamous cell carcinoma of the uterine cervix

Ten patients with squamous cell carcinoma of the cervix metastatic to periaortic lymph nodes were treated with external-beam radiation therapy and synchronous infusion of intravenous 5-fluorouracil (5-FU) chemotherapy at doses of 350 mg/m2/day. The overall response rate was 90% with four complete responses (CR) and five partial responses (PR). The median duration of response was 11.8 months for CRs and 3.6 months for PRs. Toxicity was tolerable, with gastrointestinal symptoms and myelosuppression being noted most frequently. No patient experienced life-threatening toxicity. Median survival was 7.6 months, with only one patient being alive and free of disease at 2 years. In this pilot study we were unable to demonstrate a beneficial effect of continuous infusion of low doses of 5-FU chemotherapy concurrent with radiation therapy when compared to conventional radiotherapy in patients with advanced squamous cell carcinoma of the cervix.

The role of pelvic exenteration for sarcomatous malignancies

Pelvic exenteration, although performed most frequently for recurrent squamous cell carcinoma of the cervix and vagina, has been used in selected patients with pelvic sarcoma. Nine patients with various histologic types of sarcoma treated by pelvic exenteration are reported. During this 23-year time period, 46 patients with sarcoma were evaluated for possible exenteration. Patients with embryonal rhabdomyosarcoma (sarcoma botryoides) were excluded because these pediatric tumors are now treated with less radical operative procedures, plus radiation and chemotherapy. Six patients had exenteration as primary treatment, and three patients had exenteration as secondary treatment. Four patients developed recurrent disease (mean 5.2 months), and all four died of disease. Five patients were alive at 5 and 10 years, for an absolute survival of 55%. All three patients with mixed mesodermal tumors died of recurrent disease, compared with 83% survival for patients with other sarcoma types. Pelvic exenteration may play a limited but important role in the therapy of pelvic sarcoma.

Urinary incontinence following radical vulvectomy

Although incontinence has been reported after radical vulvectomy, its relationship to operative technique, anatomy, and treatment has not been defined. Twenty-one patients having vulvectomies for vulvar cancer were prospectively evaluated preoperatively and postoperatively with urodynamic function studies. A portion of the urethra was removed in four patients undergoing radical vulvectomy, and 14 had a vulvectomy excision that came within 1 cm of the distal urethra. Six patients (28%) developed a change of continence, with three developing total incontinence, two stress incontinence, and one urge incontinence. All four patients who had a portion of the urethra excised developed stress or total incontinence. The other two patients with incontinence (one total, one urge) had the vulvectomy excision that came close to the urethra. No patient had a change in continence when surgery did not involve or come close to the urethra. When the four patients with a distal urethral resection were compared with patients in whom the urethra was not excised, there was a significant decrease postoperatively in functional urethral length (P<.0001), anatomical urethral length (P<.0001), and distal urethral pressure transmission ratios in Q3 (P=.004), Q4 (P=.02), and Q5 (P=.005); but no difference in urethral support (Q-tip test), flow rates, residual urine, bladder capacity, maximal urethral pressure, resting closure pressure, or squeeze pressure. Histologic examination of urethral specimens demonstrated that a portion of the compressor urethrae muscle was often excised. Radical vulvectomy by itself does not cause incontinence, but it would appear that removal of a portion of the urethra increases the chance of incontinence. This observation has important implications for women who are to undergo vulvectomy and for our current concepts of continence.

A comparison of staging systems for squamous cell carcinoma of the vulva

A review of 172 patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975-1989 was performed to compare the 1988 FIGO Staging System to the 1970 FIGO Staging System. The stage distribution according to the 1970 FIGO Staging System was stage I, 65; stage II, 44; stage III, 50; and stage IV, 13. The cumulative 5-year survival under the old system was stage I, 94%; stage II, 91%; stage III, 36%; and stage IV, 26%. The distribution changed under the 1988 FIGO system to stage I, 58; stage II, 36; stage III, 49; stage IVA, 16; and stage IVB, 13. The cumulative survival also changed to stage I, 94%; stage II, 89%; stage III, 71%; stage IVA, 19%; and stage IVB, 8%. The new FIGO stage distribution shifted for the worse due to the influence of positive lymph nodes found at the time of surgery. The survival was then analyzed for death from all causes. This was markedly decreased when compared to the cumulative corrected survival. This relates to the high number of other primary malignancies and the age of the patients. Among these 172 patients, other primary malignancies included squamous cell cancer of the cervix (11), squamous cell cancer of the vagina (2), endometrial cancer (3), squamous cell cancer of the lung (2), colon cancer (3), and others (6). An additional 5 patients died from myocardial infarction within 2 years of diagnosis. The new 1988 FIGO Staging System provides for better discrimination of survival between stages than the 1970 FIGO Staging System.

The surgical management of recurrent squamous cell carcinoma of the vulva

Thirty-four patients with recurrent/persistent squamous cell carcinoma of the vulva were treated at the University of Michigan Medical Center from 1975-1988. At follow-up, 19 patients (56%) were free of disease and 15 were dead of disease. Three patients developed a “bridge” recurrence, one patient each with original stages I, II, and IV. Two of these patients were free of disease and one patient died of disease. Ten patients had metastatic disease to the groin lymph nodes at the time of recurrence, and all of these patients are dead of disease. Therapy for the recurrence consisted of five radical vulvectomies (80% survival), four pelvic exenterations (25% survival), and 25 wide radical excisions (56% survival). The lymph node status was highly significant in predicting outcome, with zero of ten patients remaining free of disease when the lymph nodes were involved and 19 of 24 free of disease when the lymph nodes were uninvolved (P<.0001). Factors that did not influence survival included the institution where the initial surgery was performed and the interval from initial therapy to recurrence. Twenty patients received their initial therapy at the University of Michigan and 12 (60%) were free of disease. Fourteen patients were referred from outside institutions for their recurrence and seven (50%) were free of disease. Nineteen patients had a recurrence within 2 years and nine were free of disease, ten patients recurred between 2-10 years of whom seven were free of disease, and five patients recurred after 10 years with three free of disease. Radical excision of localized recurrent vulvar cancer provides acceptable survival results when the regional lymph nodes are not involved.