Role of sentinel lymph node (SLN) dissection
Approximately 25%–30% of the patients with vulvar carcinoma present with lymph node metastases at diagnosis.41 Groin recurrence rate may be decreased to <1% by complete groin dissection; although, this produces significant morbidities.42
The last statement also indicates that ~80%–90% of patients with vulvar carcinoma having <2 mm invasion may be spared the morbidities of groin dissection. The role of SLN dissection is probably important in this group of patients. There are some large prospective trials confirming the high sensitivity of SLN dissection compared with complete groin dissection. A meta-analysis showed an overall sensitivity of 92% for the identification of sentinel node metastases using complete inguinofemoral node dissection as the reference,43 resulting in a negative predictive value of 97%–98%. Sensitivity was further enhanced with the use of both blue dye and Tc-99m, for tumor size <4 cm and lesions located >2 cm from the midline. Sensitivity was less in patients with clinically palpable inguinal nodes.44 Another analysis summarizing published literature totalling 383 patients showed a false-negative rate of 2.4%.45
Available literature suggests that the groin recurrence rates for patients undergoing SLN dissection alone are comparable with groin recurrence rates for patients who have complete lymph node dissection. The GROningen International Study on SLNs in vulvar cancer (GROINSS-V) was the first ever large prospective multicentric study that studied 403 patients with vulvar tumor size of <4 cm, stromal invasion of >1 mm, and negative SLNs. The study compared patients who underwent SLN biopsy with those who underwent full superficial node dissection for detecting positive SLN. The study found a groin recurrence rate of 2.3% over a median follow-up period of 35 months and a very low rate of surgical complications in the SLN biopsy group.46
Imaging is recommended prior to SLN biopsy to rule out grossly affected lymph nodes. Any affected nodes have decreased uptake of radiotracer or dye and hence that may not be identified as sentinel (the statement needs clarification). No modality as of now has been proven to be the best to differentiate metastatic from normal lymph nodes.
Based on current data, women who had a negative SLN may be observed without any further evaluation. Caution, however, should be maintained when performing SLN dissections on tumors >4 cm and located in the midline. Moreover, bilateral SLN dissection should be considered in lesions within 2 cm of the midline and in all lesions that cross the midline. If an SLN is not found, then a full groin node dissection is recommended47 and if the SLN is positive, then bilateral groin node dissection is recommended. Further information is needed regarding the appropriate treatment of positive SLNs and, in particular, on the management of micrometastases.
Due to the low incidence of this cancer, absence of randomized controlled trials, and low level of evidences, no standard indications and recommendations for the different adjuvant treatment modalities are available. With available data, patients with early-stage vulvar cancer, negative groin status, and favorable prognosis, usually do not require any adjuvant treatment.
But treatment of locally advanced vulvar cancer may require further treatment modalities such as radiotherapy and chemotherapy adjuvant to surgery, to improve local control rate and survival.48 LN metastases, large primary tumors, deep invasion, lymphovascular invasion, and close surgical margins are associated with increased risk of recurrence. But the role of adjuvant radiotherapy in such patients is still unclear. In a study by Akila Viswanathan, a surgical margin ≤5 mm have been seen to have a very high local recurrence rate, and adjuvant radiation at a dose of ≥56 Gy may decrease vulvar recurrence rates.49 Radiotherapy alone or in combination with lymph node (LN) dissection is highly effective in preventing inguinal node recurrence in patients with squamous cell carcinoma of the vulva.50 Based on the study by Gynecologic Oncology Group (GOG), 37 adjuvant groin and pelvic radiotherapies are considered as the standard of care for node-positive vulvar squamous cell carcinoma for patients with 2 or more LNs involved, extracapsular extension, or inadequate LN dissection.
In several studies, substantial benefit has been achieved with the addition of postoperative radiotherapy in 2 or more cases with positive inguinal nodes.51
But the role of radiation in cases with single LN positive is unclear. Because of the limited number of patients with single LN involved, adequate power was not achieved to determine the benefit of radiotherapy. Fons et al52 could not demonstrate a significant benefit of adjuvant radiotherapy in patients with single LN metastasis in either disease-free or disease-specific survival. Recurrence rates were also found to be similar between the radiotherapy and the no-radiotherapy arms (39% vs 32%). A Surveillance Epidemiology and End Result program analysis53 demonstrated a favorable prognosis in patients with a single positive lymph node receiving radiotherapy. However, it should be noted that no information about the size and location of tumor is available in this study. Moreover, adjuvant radiation did not significantly help women who had more than 12 LNs resected. In the recent and largest ever multicentric retrospective study by the AGO-CaRE-1,54 adjuvant radiotherapy was associated with an improvement in prognosis irrespective of the number of involved lymph nodes.
A randomized trial by Homesley et al55 compared radiotherapy with pelvic lymphadenectomy in 114 patients with inguinofemoral lymph node metastasis after radical vulvectomy and inguinofemoral lymphadenectomy. The dose of radiation was 45–50 Gy delivered bilaterally to the pelvic and inguinal nodes using anterior and posterior opposing fields. The difference in the groin recurrence rates was significant, favoring the adjuvant radiation therapy (5.1% vs 23.6%, P=0.02). Survival was also found to be better in patients who received postoperative radiotherapy (2-year survival 68% vs 54%, P=0.03). A large retrospective study from India revealed a significant survival for patients receiving postoperative radiotherapy (2-year survival 68% vs 54%, P=0.03) and a lower rate of relapse (5% vs 24%, P=0.02).56
According to present evidences, adjuvant radiotherapy to the groins and pelvis must be recommended after radical groin dissection when there are 2 or more affected lymph nodes or in the case of 1 lymph node metastasis with extracapsular spread or large size. This could be explained by the way of the fact that in 20%–30% of the patients with inguinofemoral lymph node metastases, pelvic lymph nodes are also affected.57 In such patients, irradiation of the vulva may also be considered, though evidences regarding this are low. In the case of only 1 intracapsular metastasis, the role of radiotherapy is currently unclear and needs further investigation.