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and the no-radiotherapy group (39% versus 32%). In multivariate subanalysis performed as part of
the AGO-CaRE-1 study218 (163 patients), adjuvant radiotherapy was associated with a not
statistically significant better PFS compared to patients without adjuvant treatment (adjustment for
age, Eastern cooperative oncology group (ECOG) performance status, Union internationale contre le
cancer (UICC) stage, grade, and invasion depth: HR = 0.88, 95% CI = 0.50-1.56, p = 0.67). Similar
results were obtained after control for multiple confounding factors by inverse probability of
treatment weighting (HRIPTW = 0.93, 95% CI = 0.51-1.67, p = 0.79).

Parthasarathy et al.219 have for their part reported a favourable 5-y disease specific survival (DSS) in
patients receiving adjuvant radiation. Controlling for age at diagnosis and extent of
lymphadenectomy, their data suggest that adjuvant radiation may improve the survival of these
patients although this only reached borderline statistical significance (HR = 0.57, 95% CI = 0.32-
1.03, p = 0.06). However, it should be noted that no information about the size and location of
tumour is available in this study. Moreover, adjuvant radiation did not significantly benefit women
who had more than 12 nodes resected (66.7 versus 77.3%, p = 0.23).

Adjuvant radiotherapy (multiple positive nodes): a randomised trial compared pelvic radiotherapy LoE 1+
with pelvic lymphadenectomy in 114 patients with inguinofemoral lymph node metastases after
radical vulvectomy and bilateral inguinofemoral lymphadenectomy220. The difference in regional
(groin) recurrence was significant, favouring the adjunctive radiation therapy group (5.1% versus
23.6%, p = 0.02). Survival proved also to be better in the patients who received postoperative
radiotherapy (overall survival (p = 0.03), relative survival (0.004), progression-free interval (0.03)).
In this study, the most dramatic survival advantage for radiation therapy was in patients who had
either of the two major poor prognostic factors present: 1) clinically suspicious or fixed ulcerated
groin nodes, and 2) two or more positive groin nodes. The long time results of this trial revealed a
persistent benefit for patients treated with pelvic irradiation221.

After a median survival follow-up of 74 months, the OS benefit for radiation in patients with
clinically suspected or fixed ulcerated groin nodes (p = 0.04) and two or more positive groin nodes
(p < 0.001) persisted. The relative risk of progression was significantly reduced in radiation patients
(HR = 0.39, 95% CI = 0.17-0.88, p = 0.02) after adjustment for age and adverse tumour
characteristics. Moreover, the cancer-related death rate was significantly higher for pelvic node
resection compared with radiation (HR = 0.49, 95% CI = 0.28-0.87, p = 0.015). The proportion of
patients developing post-operative wound infections, urinary tract infection, and other adverse
sequelae were similar between treatment approaches. However, it should be noted that patients with
positive groin nodes in the surgery group in this study did not receive adjuvant radiotherapy to the
groins.

In multivariate analysis of different nodal subgroups performed as part of the AGO-CaRE-1 study218 LoE 2+
(adjustment for age, ECOG performance status, UICC stage, grade, and invasion depth) adjuvant
radiotherapy was associated with statistically significant better progression-free survival (PFS) in
patients with two positive nodes (91 patients, HR = 0.31, 95 CI 0.14-0.71, p = 0.005), and in patients
with three positive nodes (56 patients, HR = 0.40, 95% CI = 0.16-0.98, p = 0.05) compared to
patients without adjuvant treatment. Similar results were obtained after control for multiple
confounding factors by inverse probability of treatment weighting (two positive nodes: HRIPTW =
0.24, 95% CI = 0.11-0.56, p < 0.001; three positive nodes: HPIPTW = 0.32, 95% CI = 0.13-0.79, p =
0.009). The benefit of adjuvant radiotherapy among patients with more than three positive nodes did
not reach statistical significance (21 patients, HR = 0.52, 95% CI = 0.24-1.10, p = 0.09/HRIPTW =
0.44, 95% CI = 0.17-1.17, p = 0.10).

11.2 Previous initiatives

Eight previous initiatives1-4,37-39,87 presenting guidelines on radiation therapy were identified.

 VULVAR CANCER - GUIDELINES 
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