Gynecologic Oncology Group randomized trials of combined technique therapy for vulvar cancer.

Keys H. The Gynecologic Oncology Group (GOG) did a surgicopathologic study of vulvar cancer in which various prognostic factors in the primary lesion were evaluated and compared with the pathologic status of the lymph nodes in the groin dissections. In total, 558 patients were entered into this study (GOG Protocol 36) from November 1977 to February 1984. The 203 patients with positive groin nodes were eligible for a second study in which they were assigned randomly to receive either pelvic lymph node dissection or pelvic and groin irradiation (Protocol 37). One hundred fourteen patients were randomized to this study, and 53 of 59 patients in each treatment arm actually underwent the prescribed treatment. Acute and late toxicities were similar in both treatment arms. There was a significant difference in survival rate that favored the pelvic radiation treatment (P = 0.03). The largest difference in survival rates occurred in those patients with either of the poor prognostic findings (clinically suspicious fixed ulcerated nodes or two or more positive nodes). The 2-year survival rate was 68% for the radiation treatment arm and 54% for the surgical program. Pelvic radiation therapy has become the standard treatment for patients with positive groin nodes, especially if they are fixed or multiple. Based on these results, a subsequent study was designed to test whether radiation therapy could substitute for bilateral groin node dissection in patients with vulvar cancer (Protocol 88). Fifty-eight patients were enrolled in the study before entry was suspended on April 30, 1991, and the study was closed on November 1, 1991. In the first 49 evaluable patients, there were five groin recurrences in the irradiated patients, although there were no groin failures in the operated group. The radiation program used in this study may not have provided an adequate dose to the depth where the lymph nodes were located because the prescription called for dose calculations at a depth of 3 cm. Unless demonstrated in another study, groin irradiation cannot be used as an equivalent option to groin dissection. Aggressive preoperative chemoradiation treatment currently is being studied for patients with T3 lesions not amenable to standard radical vulvectomy. Surgical dissection of residual tumor plus bilateral groin dissections are to be done if the postradiation biopsy findings are positive. Patients with unresectable Stage T2 or T3 groin nodes are also eligible for this study (Protocol 101).

Obstet Gynecol 1986 Dec;68(6):733-40

Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes.

Homesley. 114 eligible patients with invasive squamous cell carcinoma of the vulva and positive groin nodes after radical vulvectomy and bilateral groin lymphadenectomy were randomized to receive either radiation therapy or pelvic node resection. Fifty-three of the 59 patients randomized to radiation therapy received a 4500- to 5000-rad tumor dose in five to 6.5 weeks bilaterally to the groins and to the midplane of the pelvis even if only unilateral positive groin nodes had been detected; no radiation was given to the central vulvar area. Fifty-three of the 55 patients randomized to further surgery had pelvic node resection performed on the side containing positive groin nodes either unilaterally or bilaterally. Acute and chronic morbidity was similar for both regimens. The two major poor prognostic factors were clinically suspicious or fixed ulcerated groin nodes and two or more positive groin nodes. The difference in survival for the 114 evaluable patients was significant, favoring the adjunctive radiation therapy group (P = .03). The estimated two-year survival rates were 68% for the radiation therapy group and 54% for pelvic node resection group. The most dramatic survival advantage for radiation therapy was in patients who had either of the two major poor prognostic factors present; at this time, the benefit of radiation therapy for the remaining patients is uncertain. In this randomized prospective study, the addition of adjunctive groin and pelvic irradiation therapy after radical vulvectomy and inguinal lymphadenectomy proved superior to pelvic node resection.

Int J Radiat Oncol Biol Phys 1992;24(2):389-96

Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study.

Stehman Members of the Gynecologic Oncology Group randomized 58 patients with squamous carcinoma of the vulva and nonsuspicious (N0-1) inguinal nodes to receive either groin dissection or groin radiation, each in conjunction with radical vulvectomy. Radiation therapy consisted of a dose of 50 Gray given in daily 200 centiGray fractions to a depth of 3 cm below the anterior skin surface. RESULTS: The study was closed prematurely when interim monitoring revealed an excessive number of groin relapses on the groin radiation regimen. Metastatic involvement of the groin nodes was projected to occur in 24% of patients based on this Group's previous experience. On the groin dissection regimen, there were 5/25 (20.0%) patients with positive groin nodes. These patients received post-operative radiation. There were five groin relapses among the 27 (18.5%) patients on the groin radiation regimen and none on the groin dissection regimen. The groin dissection regimen had significantly better progression-free interval (p = 0.03) and survival (p = 0.04). CONCLUSION: Radiation of the intact groins as given in this study is significantly inferior to groin dissection in patients with squamous carcinoma of the vulva and N0-1 nodes.

Int J Radiat Oncol Biol Phys 1993 Nov 15;27(4):963-7

Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used.

Petereit. University of Wisconsin Medical School. To update a previous retrospective study that compared inguinofemoral irradiation (N = 23) to lymphadenectomy (N = 25) for N0,N1 vulvar carcinoma with more patients and longer follow-up. These results, unlike the recent randomized Gynecologic Oncology Group (GOG study), suggest that radiation is a viable alternative to groin dissection, and the differences may be explained on the basis of irradiation technique. the decision was made to offer patients with squamous cell carcinoma of the vulva and clinically negative groins (N0,N1), either lymphadenectomy or inguinofemoral irradiation based on clinical factors. Because of the acute skin reaction and possible underdosing of deep femoral nodes with electrons as used in the GOG study, opposed photon fields to 50 Gy were used. From 1983 to 1991, 48 patients underwent a radical vulvectomy followed by either lymphadenectomy (Group I, n = 25) or inguinofemoral irradiation (Group II, n = 23). RESULTS: The actuarial nodal control was 100% in Group I and 91% in Group II (p = 0.14). In addition, there was no difference in cause specific survival at 3 years (96% and 90%, respectively, p = 0.47). The morbidity of lymphadenectomy (Group I) included: 16% lymphedema, 16% seromas, 44% infection, and 68% wound separation. In the irradiated patients (Group II), 16% developed lymphedema and only 9% had a significant skin reaction. CONCLUSION: Based on this analysis of local control and survival with longer follow-up and more patients, irradiation of the N0, N1 inguinofemoral nodes may be a viable alternative to lymphadenectomy for squamous cell carcinoma of the vulva if proper radiation technique and dose are used. In addition, the acute and delayed morbidity of lymphadenectomy exceeds that of irradiation.

Int J Radiat Oncol Biol Phys 1997 Jul 1;38(4):749-53

Does T1, N0-1 vulvar cancer treated by vulvectomy but not lymphadenectomy need inguinofemoral radiation?

Manavi. University of Vienna, Austria. 135 patients with invasive vulvar carcinoma in Stage T1 without clinical evidence of inguinal lymph node involvement underwent simple vulvectomy performed by hot-knife resection without lymphadenectomy. Although 65 patients (Group 1) received postoperative inguinofemoral radiation therapy, 70 patients (Group 2) did not, and none received local vulva irradiation.The 5-year survival rates were 93.7% in Group 1 and 91.4% in Group 2. The complication rates were, 7.7% in Group 1 and 2.9% in Group 2, 2.7% for vaginal stenosis (two patients in each group), 1.5% for inguinal pain (one patient in Group 1), 1.5% for rectovaginal fistula (one patient in Group 1), 1.5% for vulvar infection (one patient in Group 1). The 5-year survival rates in both groups were similar to those reported in the literature for radical vulvectomy and inguinal lymph-node dissection (83-96%).  Although our data showed similar results in both groups, we are not recommending at this time to omit groin radiation in general, but it may be justified in low-risk cases.

Int J Radiat Oncol Biol Phys 2000 Nov 1;48(4):1007-13

Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.

Montana GS, Thomas GM, Moore DH, Saxer A, Mangan CE, Lentz SS, Averette HE

Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.

Purpose: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation.Methods and Materials: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery.

Results: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. Conclusion: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.