VWOG richtlijn vulvacarcinoom Herfst symposiumVVOG Kinepolis Brugge Frédéric Amant Namens VWOG bestuur

Tissue is the issue! Vulvar intraepithelial disease Squamous cell carcinoma (90%) Verrucoid cancer Basal cell ca Adenocarcinoma Paget’s disease Bartholin gland carcinoma (40% squamous) Melanoma Malignant mesenchymal tumors Metastatic

VIN III: Triad of three P’s: parakeratosis, pigment, papulae

Vulvar Intraepithelial Neoplasia Low grade VIN: subclinical HPV infection High grade VIN: - moderate to severe dysplasia - undisputed malignant potential - 30-50% co-existence with vulvar ca - S/ no, pruritus, burning, pain, dysuria - R/ surgical excision (laser, cold knife)

Diagnostic work-out KO: operability & groin Chest X-ray CT abdomen, inclusive groin SCC in blood On indication: recto- en cystoscopy, CT-thorax

Treatment modalities in vulvar cancer Stage Ia (< 1mm depth of invasion  0% + inguin LN partial vulvectomy Stage Ib-III (partial) vulvectomy inguinofemoral lymphadenectomy/ sentinel node procedure Stage IVa exenteration/neoadjuvant CT/45-65Gy Stage IVb palliation

Total vulvectomy

The price of less radical surgery Surgical tumor-free margin > 8 mm: no vulvar recurrence, n=91 < 8 mm: 21/44 (48%) vulvar recurrence Heaps et al., Gynecol Oncol 1990;38:309-14 >8 mm: no vulvar recurrence, n=39 < 8 mm: 9/40 (22.5%) vulvar recurrence de Hullu et al., Cancer 2002;95:2331-8

What is an adequate resection margin. Ibrahim et al What is an adequate resection margin? Ibrahim et al., IGCS 2006, Santa Monica Abstract 36 15 consecutive patients At least 10 mm clear margin macroscopically Reduction of clear margin 15% post resection 15% tissue fixation 15% microscopically Totalling 45% reduction 1 cm is insufficient as macroscopic margin

With urethral resection Without urethral resection (n=17) Impact of partial (< 1.5 cm) urethral resection de mooij et al., Int J Gynecol Cancer 2007;17:294-7 With urethral resection (n=18) Without urethral resection (n=17) P-value Preoperative 0.502 Continent 13(72%) 13(76%) Incontinent 3(17%) 1(6%) Unknown 2(11%) 3(18%) Postoperative 0.860 14(78%) 15(88%) 4(22%) 2(12%) Questionnaire 0.494 6/8 (75%) 9/12(75%) 2/8(25%) 3/12(25%)

femoral artery and vein M Pectineus m adductor longus M abdominis, sheet femoral artery and vein M sartorius

Apex of the femoral triangle vein Sartorius muscle Femoral artery

Ipsilateral superficial inguinal lymphadenectomy Stehman et al Ipsilateral superficial inguinal lymphadenectomy Stehman et al., Obstet Gynecol 1992;79:490-7 Prospective evaluation N = 155 7.3% inguinal recurrence rate Historical control: 0% inguinal recurrence rate Recurrence rate varies from 0-8.6% (Berman 1989; Stehman 1992; Burke 1995; Gordinier 2003; Kirby 2005) Number of recurrences attributable to decision to leave the femoral nodes

SLN plus lymphadenectomy Sentinel node dissection is safe in the treatment of early-stage vulvar cancer: morbidity Van der Zee et al., JCO 2008;26:884-9 Morbidity SLN dissection only SLN plus lymphadenectomy P Short term Total N° of patients 264 47 Wound breakdown, n (%) 31 (11.7) 16 (34.0) < .0001 Cellulitis, n (%) 12 (4.5) 10 (21.3) Hospital stay, days 8.4 13.7 Long term 119 Lymphedema, n (%) 5 (1.9) 30 (25.2) Recurrent erisipelas, n (%) 1 (0.4) 19 (16.2)

Fig 2. (A) Cumulative proportion of groin recurrences in patients with unifocal vulvar cancer < 4 cm and negative sentinel node (dark blue line); 95% CIs are also given (light blue lines) 6/259 (2.3%) 97% 3y survival Van der Zee, A. G.J. et al. J Clin Oncol; 26:884-889 2008

Sentinel node dissection is safe in the treatment of early-stage vulvar cancer: quality control at each step Van der Zee et al., JCO 2008;26:884-9 Injection of radioactive tracer Interpretation of lymphoscintigram Surgeon: 10 patients/year/surgeon Pathology: experience with ultrastaging

Flow chart sentinelklierprocedure de Hullu et al Flow chart sentinelklierprocedure de Hullu et al., Gynecol Oncol 2004;94:10-5 Patient met T1 of T2 (<4cm) vulvair carcinoom zonder verdachte liezen Radiologie (Ct of MR) om verdachte klieren te identificeren; zo verdacht echografie + fijne naald aspiratie Metastase: volledige lymphadenectomie Geen metastase Geen sentinel lymfeklier: technisch falen? Logistiek probleem? Sentinel lymfeklier procedure met gecombineerde techniek (preoperatief lymphoscintigraphy met 99m Technetium gelabeld nanocolloid en patent blauw). Verwijderde SLNs voor vriescoupe. Intraoperatieve palpatie om vaste lymfeklieren te voelen. Patholoog informeert gynaecoloog over aantal SLN’s. Brede locale excisie. In liezen met een positieve SLN bij vriescoupe een volledige inguinofemorale lymphadenectomie. Bij problemen ter identificatie van de SLNs eerst verwijderen primaire tumor om radioactiviteit te verminderen en nadien de SLN’s Definitieve pathologie: (micro) metastase in SLN(‘s): secundaire volledige lymphadenectomie. Ja: herhaal procedure Nee: volledige inguinofemorale lymphadenectomie Zo meer dan 1 intranodale metastase of extranodale groei: postoperatieve radiotherapie FOLLOW-UP

< 8 mm resection margin Significant lymfatic permeation Indications for postop radiochemotherapy of the groin and ipsilateral hemipelvis Vulvar > 4 cm Ø < 8 mm resection margin Significant lymfatic permeation Inguinofemoral Macrosc + nodes  2 microscopic nodes