Treatment Protocols
Primary vulvar cancer is rare; American Cancer Society estimates for 2021 are for 6120 new cases and 1550 deaths. [1] More than 90% of vulvar cancers are squamous cell carcinomas. Other histologies, such as melanoma, adenocarcinoma, sarcoma, and basal cell carcinoma, are less common. [2] The treatment of vulvar cancer in this article focuses on squamous cell histology and does not include the treatment of preinvasive disease.
Early-stage vulvar cancer (stage I-II)
Treatment recommendations are as follows:
-
Reexcision may be considered if margins are positive or < 8 mm [4] ; however, a literature review by Milliken et al concluded that "a surgical resection margin of 2-3 mm does not appear to be associated with a higher rate of local recurrence than the widely used limit of 8 mm." [5] Alternatively, adjuvant radiation may be used rather than reexcision, especially if a repeat procedure would result in excessive morbidity [6]
-
Adjuvant radiation is based on pathologic risk factors (see below)
-
Stage II with extension to the distal third of the urethra or distal third of the vagina or with anal involvement can be treated with radical local excision with bilateral inguinofemoral lymphadenectomy; radiation to these regions can also be considered
Table 1. Summary of Indications for Inguinofemoral Lymphadenectomy [9] (Open Table in a new window)
Inguinofemoral lymphadenectomy |
Tumor size (cm) |
Stromal invasion (mm) |
No lymph node dissection required |
≤2 cm |
≤1 (without lymphovascular space involvement) |
Ipsilateral |
≤2 cm |
≤1 (plus lymphovascular space involvement) |
≤2 cm |
>1 mm |
|
>2 cm |
Any |
|
Bilateral |
Same as ipsilateral and - Midline tumor (< 1 cm) or - Involves anterior labia minora or - Positive ipsilateral lymph node (if lesion ≥2 cm and depth ≥5 mm) [10] |
|
Indications for adjuvant treatment of metastatic groin lymph nodes include the following [11] :
-
One lymph node micrometastasis (< 5 mm): No adjuvant radiotherapy
-
Any lymph node macrometastasis ≥5 mm: Adjuvant radiotherapy
-
Two or more lymph node micrometastases (< 5 mm): Adjuvant radiotherapy, including inguinal and pelvic fields
-
Any extracapsular spread: Adjuvant radiotherapy, 45 Gy in 25 fractions [11]
Oonk et al examined the size of the metastatic disease in sentinel lymph nodes and found that micrometastasis >2 mm carried a risk of recurrence; the investigators suggested that adjuvant treatment or completion inguinofemoral lymph node dissection be performed for such sentinel lymph nodes. [12]
A National Cancer Data Base (NCDB) analysis of 1797 patients with vulvar cancer who underwent extirpative surgery with confirmed inguinal nodal involvement treated with adjuvant radiotherapy concluded that the addition of adjuvant chemotherapy resulted in a 38% reduction in mortality risk. Unadjusted median survival with and without adjuvant chemotherapy was 44.0 versus 29.7 months, respectively (P=0.001). [13]
Locally advanced vulvar cancer (bulky stage III and stage IV)
Treatment recommendations are as follows:
-
There is no significant difference in overall survival rates or in treatment-related adverse events when chemoradiation (primary or neoadjuvant) is compared with primary surgery [14]
-
Radical surgery (radical vulvectomy plus bilateral lymphadenectomy): If partial removal of other involved structures is needed (eg, urethra, vagina, anus, bladder, rectum) and/or pelvic exenteration is necessary, consider preoperative chemoradiation
-
Concurrent chemotherapy: Most cancer centers have extrapolated from the cervical cancer literature and use weekly cisplatin as a chemosensitizer [18] ; a phase II study documented the safety and efficacy of weekly cisplatin (40 mg/m2 IV, not to exceed 70 mg/dose) [17, 19] ; previously studied regimens have included cisplatin plus 5FU [15, 20] and 5FU plus mitomycin C, [21] but these are not as commonly used
Metastatic vulvar cancer (stage IVB)
There are no standard treatment guidelines for metastatic vulvar cancer; however, the following should be noted:
-
Chemotherapy regimens for metastatic vulvar cancer are similar to those used for metastatic cervical cancer
-
Combinations of chemotherapy and radiation can be considered
Recurrent vulvar cancer
Recurrent vulvar cancer can be grouped into local (regional), groin, and distant categories, and the following should be noted:
-
Local recurrence carries a good prognosis and can be treated with resection or radiation
-
Recurrences in the groin carry a poor prognosis; a select few of these patients may benefit from surgical resection and radiation
-
Distant recurrence is treated with chemotherapy; paclitaxel has been used as a single agent [27]
-
Pembrolizumab was approved as second-line therapy for programmed death ligand 1 (PD-L1)-positive or microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) tumors. The US Food and Drug Administration also granted accelerated approval for unresectable or metastatic tumor mutational burden–high (TMB-H) (≥10 mutations/Mb) solid tumors in patients whose disease has progressed following prior treatment and who have no alternative treatment options. [28]
Tables
Inguinofemoral lymphadenectomy |
Tumor size (cm) |
Stromal invasion (mm) |
No lymph node dissection required |
≤2 cm |
≤1 (without lymphovascular space involvement) |
Ipsilateral |
≤2 cm |
≤1 (plus lymphovascular space involvement) |
≤2 cm |
>1 mm |
|
>2 cm |
Any |
|
Bilateral |
Same as ipsilateral and - Midline tumor (< 1 cm) or - Involves anterior labia minora or - Positive ipsilateral lymph node (if lesion ≥2 cm and depth ≥5 mm) [10] |
|
