actualizacion en el manejo del cancer de vulva

1. Actualización en
Carcinoma Invasor de Vulva
Cirugía y Radioterapia.
Begoña Díaz de la Noval
Fellow Unidad de Oncología-Ginecológica

2. Epidemiología
• Poco frecuente 4% - 4º
• >70a
• Alta comorbilidad.
• Histología:
– Carcinoma escamoso (90%)
– Melanoma maligno
– Paget Vulvar.
– Adenocarcinoma.
– Carcinoma Basaloide.
– Carcinoma de Glándula de
Bartolino

3. Diagnóstico
• Clínico
• Lesiones premalignas: liquen,
Paget, Bowen, Queyrat.
• Labio mayor > menor >
clítoris > periné.
• 5% multifocal.
• No screening
• 20% localmente avanzado
• Biopsia dirigida (estroma)

4. Estadificación quirúrgica FIGO 2009

5. Factores Pronósticos
Supervivencia a 5a: media 75%
Estadio I: 90%
Estadio II: 70-75%
E III: 40-25%
E IV: 20%
Márgen <8mm
ILV+
Infiltración >4-5mm
Tamaño ≥4cm

6. Taussig y Way (1940): disección radical en
Bloque (Supervivencia a 5a 60-70%)
• IUE
• osteomielitis púbica
• fístula rectovaginal o
rectoperineal
Tratamiento Quirúrgico
Carcinoma Invasor de Vulva
• Lesión vascular
• Mal cicatrización (dehiscencia, seroma, hernia)
• Tromboembolismo
• Linfedema (62%), Linfangitis (10%)
• Dolor crónico en MMII
• Alteración imagen corporal o sexualidad

7. Triple incisión
Hemivulvectomía
Linfadenectomía
ipsilateral

8. • Objetivo
– Control local de la
enfermedad.
• “radicalidad” con intención curativa.
– Control a distancia: afectación
ganglionar locorregional.
•BSGC
Tratamiento Quirúrgico
Actual del Carcinoma Invasor de Vulva

9. CONTROL LOCAL
Exéresis del Tumor
– Márgen quirúrgico 20mm.
• 10mm en zonas inevitables (uretra, ano).
• Márgen histológico ≥8mm.
De Hullu, Cancer 2002;95:2331-8.
Heaps JM. Surgical pathologic variables predictive of local recurrence in
squamous cell carcinoma of the vulva. Gynecol Oncol 1990 sep;
38(3):309-14.
– Excisión radical o profunda: hasta la fascia inferior del
diafragma urogenital.

10. Técnica: 1. Excisión Local
Radical Amplia
• IA
– No BSGC: ≤1mm invasión estromal G+<5%
• IB con T<4cm, invasión ≤5mm.
• No aumento de las recurrencias locales.
Iacoponi S. Análisis de Factores asociados a recurrencia
local en cáncer de vulva. Tesis doctoral, 2013.

11. 2. Hemi-Vulvectomía Radical
Modificada
– Exéresis radical de toda el área vulvar,
– IB T≥4cm, invasión estromal >5mm, ILV+
– <1cm de línea media, multicentricidad
– E≥II

12. 3. Exenteración Pelviana
– IVA sin afectación de pared
pélvica y/o ganglios
resecables.
– Recaida externa y limitada a la
región pélvica.
– Agotadas las alternativas
terapeúticas.
– No diseminación de la
enfermedad.
– Intención curativa (paliativa).

13. Oncoplastia
• Injerto de piel o Skin Graft
• Colgajo o Skin Flap:
– Cutáneo: piel + tejido subcutáneo
– Fasciocutáneo: + fascia
– Miocutáneo: + músculo

14. Colgajo/Flap
• Defectos anteriores o laterales:
– Z-plastia: Colgajo fasciocutáneo de avance en V o Y.
– Colgajo subcutáneo de pared abdominal inferior (a epigástrica superficial)
• Pequeños defectos.
– Colgajo fasciocutáneo neurovascular pudendo o de Singapur (a pudenda int).
– Colgajo miocutáneo gracilis (a circunfleja femoral medial), defectos medios.
– Colgajo miocutáneo tensor de la fascia lata
• Defectos posteriores:
– Colgajo miocutáneo recto abdominal (TRAM), grandes defectos.
– Colgajo fasciocutáneo glúteo (a. glútea inferior)
• Neovagina:
– Colgajo miocutáneo gracilis bilateral
– TRAM

15. Plastia simple. Colgajo de Avance V-Y

16. Z-plastia y Colgajo de Avance V-Y

17. Colgajo Fasciocutáneo Neurovascular
Pudendo o de Singapur

18. Colgajo miocutáneo Gracilis

19. Colgajo miocutáneo Gracilis

20. Colgajo miocutáneo Tensor de la Fascia
Lata

21. Fasciocutáneo Glúteo de Avance en Y

22. Neovagina- C Miocut Recto Abdom
Tubular (TRAM)

23. Neovagina- C Miocut Gracilis BL

24. CONTROL A DISTANCIA
DETECCION Y TRATAMIENTO DE LA
AFECTACION GANGLIONAR:
BSGC
• Menor morbilidad
• Focalizar el estudio histológico

25. BSGC
Técnica combinada (S 90-95%)
PreQx: TC99 nanocoloide de albúmina 0,5 mCi/0,15 ml
(18 mBq) x 4 Inyecciones peritumorales.
Qx: Azul / Verde 2 ml peritumoral.
Detección: PreQx: SPET-TC
Qx: Gamma-Sonda manual portátil
Qx: Visualización colorante
Extracción: GC caliente y/o azul (>10%) 1 ó 2
Ultraestadificación

26. Estadios
Quirúrgicos
I, II, III.
Indicaciones BSGC:
IB ó II, <4cm, unifocal, N0
clínico-radiológico.
Bilateralidad
S 97% FN 2%.
2% linfedema
Macrometástasis (≥2mm) o
Micrometástasis ( >0,2mm-
<2mm): Linfa inguino-femoral bl.
Células tumorales aisladas o
metástasis <0,2mm: Observación

27. Linfadenectomía Inguino-Femoral
Bilateral
≥4cm, multifocal, III, no posible GC, sospecha
clínico-radiológica o demostrada afectación
ganglionar.
La tasa de afectación global es del 10-15 % por lo
que en un 85-90 % la linfadenectomía es sólo un
procedimiento diagnóstico con una alta
morbilidad.
Radioterapia en ganglios + no es mejor que cirugia,
a pesar de menor morbilidad, tiene mayor
recurrencia y menor supervivecia.
Cochrane 2011

28. Linfadenectomía InguinoFemoral con
preservación de la Fascia del Femoral (90)

29. ¿Cuántos Ganglios?
Al menos 10-12 ganglios resecados (bilateral)
para un manejo óptimo.
Menos de 15 ganglios totales tiene un impacto
negativo en la supervivencia.
– Al menos 10 ganglios en la disección unilateral.
Benedetti Panici P et al. Prognostic role of inguinal lymphadenectomy in
vulvar squamous carcinoma. Gynecol Oncol 2015 (137):373-9.

30. Seguimiento
III-IV: TAC t-a-p
c/ 6mx2a –
12m/5a

31. Cirugía en la Recidiva
• Local: vulvar o perineal
– c/s RT previa.
• Regional: Ganglionar.
– Individualizar
• Enfermedad localmente avanzada y/o
agotadas las opciones terapeúticas.
– A distancia: Paliativo
• Exéresis: local amplia, vulvectomía radical,
exenteración pélvica c/s linfadenectomía.
Biopsia + RM pélvica
+ PET-TC

32. Conclusiones. Papel de la Cirugía
en el Cáncer de Vulva
Estadificación correcta.
Factores pronósticos.
• La cirugía es el estándar:
– Control local de la enfermedad.
• “Radicalidad” curativa.
• Recaída y Paliación.
– Control a distancia: ganglionar.
• Multidisciplinar e individualizado:
Oncoplastia, RT-BT y QMT.

33. Radioterapia en cáncer de vulva
Isabel Rodríguez
Oncología Radioterápica

34. MOST DEATHS ARE DUE TO UNCONTROLLED LOCOREGIONAL DISEASE
Risk of groin node metastasis
 Lymphovascular space invasion
 Deep stromal invasion of >5mm
 Large primary tumor size
 Positive or close surgical margins (8mm)
Risk of local recurrence
Risk of local recurrence

35. SURGERY
1st scenario
Early disease
(STI-STII)
VULVAR CANCER
Close margins (<8mm)
+ margins
LVSI
Invasion >5mm
Tumor ≥ 4cm
Adjuvant Radiotherapy
Objective
 LRR
 OS

36. AGAINST - Groenen SM et al. 2010
- Höckel M et al. 2010
- Woelber L et al. 2011
- Catanzarite T et al. 2012
FOR - Heaps JM et al. 1990
- Faul CM et al. 1997*
- De Hullu JA et al. 2002
- Chan JK et al. 2007
Postoperative RT reduce LRR
from 58% to 16% in:
• close/positive margins
Postoperative RT improve OS in:
• positive margins
No difference in LRR
*
Adjuvant RT
Close margins (<8mm)
+ margins
VULVAR CANCER
Summary I
In the absence of robust evidence, adjuvant local RT should be
offered if re-excision will not be possible, since recurrence has a
poor prognosis regardless of any salvage treatment.
Salom EM. Curr Treat Options 2002

37. AGAINST - Rouzier R et al. 2002
- Tantipalakorn C et al. 2009
FOR - Burger MP et al. 1995
- Katz A et al. 2003
- Chan JK et al. 2007
VULVAR CANCER
* GOG 145 …
This controversy reflects the ongoing problem of a lack of reliable
prognostic factors, especially in node-negative vulvar cancer.
Adjuvant RT
Adjuvant local RT should be offered, since recurrence has a
poor prognosis regardless of any salvage treatment.
Summary II

38. Technical aspects
• Radiotherapy (EBRT) • Brachytherapy
VULVAR CANCER
ADJUVANT RT
Target volume = primary tumor bed
Early disease

39. Adjuvant RT
to the nodal region
is less controversial.
radical vulvectomy
±partial resection of
surrounding organs
2nd scenario
Locally
advanced ST
III
VULVAR CANCER
 + inguinofemoral lymph node affectation is the most important
prognostic factor (for recurrence and survival ) in vulvar cancer
 Large primary tumors (≥ 4cm) and LVSI also correlate with an
increased risk for local recurrence in vulvar cancer
Homesley HD et al. 1986 / 1991, Burger MP et al. 1995, Beller U et al. 2006

40. At present, only patients with 2 or more + lymph nodes or at least 1
with ECI are treated with adjuvant radiotherapy, based on…
Gynecol Oncol 1992, Cancer 1994,Cancer 1995,
Gynecol Oncol 2004, Obstet Gynecol 2009
However, growing evidence show that patients with only 1 nodal
macrometastasis might benefit from adjuvant treatment.
Curr Opin Oncol 2010, Int J Gynecol Cancer 2012
VULVAR CANCER
Adjuvant RT
Results from the largest retrospective multicenter study on vulvar cancer
(AGO CaRE-1) with more than 1600 patients showed an improvement in
prognosis from adjuvant radiotherapy irrespective of the number of nodes
affected.
J Clin Oncol 2012
Evidence

41. The potential benefit of chemoradiation for node-positive vulvar cancer
has not been systematically addressed.
Some studies with small number of patients showed a benefit in
survival although the difference was not statistically significant.
Han SC et al. Int J Radiat Oncol Biol Phys 2000
VULVAR CANCER
Adjuvant RT + CHT
Evidence

42. Currently, adjuvant radiotherapy of the groin and pelvis should be
recommended after radical groin dissection in the case of:
•2 or more affected lymph nodes
•1 affected lymph node with ECI or an enlarged lymph node
VULVAR CANCER
Adjuvant RT
In the case of only 1 intracapsular metastasis, the role of
radiotherapy is of unclear significance.
Burger MP et al. 1995, Woelber et al.2009
However, adding adjuvant RT to the primary tumor bed should be
decided based on pathological prognostic factors.
SummaryLocally
advanced ST
III

43. INCREASE IN TOXICITY
NEOADJUVANT APPROACH
EMERGED
Plastic
reconstruction
procedures
are often
necesary
High complication rates
10% operative mortality
Quality of life
Need for adjuvant treatments
(RT / RT+CHT)
pelvic
exenteration
3rd scenario
Locally advanced
ST IV

44. downsizing/downstaging
Avoid pelvic exenteration
Without comprimising survival
VULVAR CANCER
Neoadjuvant…

45. Neoadjuvant RT
Neoadjuvant CHT
… 80’s
Boronow RC 1982,1987; Hacker NF 1984
 downsizing 70-85% of p
 5-year survival 72%
 Overall RR 56%
 33% pathological downstaging
… 90’s
Durrant 1990, Benedetti-Panici 1993
VULVAR CANCER
Neoadjuvant…
Evidence

46. EVIDENCE
• The GOG (101) Phase II trial to
determine the feasibility of using
preoperative CHT-RT to treat
unresectable T3 or T4 tumors
5-Fu + CDDP
RT doses of 47.6 Gy – split course
 high RR and improved local control
 RR of 33/71 (46.5%).
 At a median FU of 50 months:
- 54.9% were alive and without
evidence of recurrent disease.
 Toxicity was acceptable
 38/46 N2-N3 (95%) resectable
 20% were alive and without
evidence of recurrent disease
Year 1998
Year 2000
Neoadjuvant
RT + CHT

47. • The GOG (205) Phase II trial to assess the
efficacy and toxicity of using preoperative
CHT-RT* (w/cisplatin +d/RT) to treat
unresectable T3 or T4 tumors . *Dose 57,6 Gy
 cCR in 64% (37/58)
 78% pCR (50% of total)
 69% completed treatment
Year 2012
Neoadjuvant
RT + CHT
Conclusion
This combination of RT plus weekly cisplatin produce high clinical
and pathologic complete response rates with acceptable toxicity
Summary
Standard treatment for locally advanced vulvar cancer includes
neoadjuvant chemoradiotherapy with weekly cisplatin and doses
of RT above 47.6 Gy.
Locally advanced
ST IV

48. Definitive RT + CHT
Neoadjuvant RT + CHT
Definitive RT + CHT
Surgery
Conclusions
No significant difference
between chemoradiation and
primary surgery in:
 OS
Treatment-related AE
No data on QL
Effectiveness and safety
 2 retrospectives studies
 1 RCT
or
compared to
REVIEW (year 2011)

49. Radiation Treatment
Treatment volume
Dose
Techniques
EBRT
 3DCRT
 IMRT
 Vulva
 Bilateral iliac nodal areas
 Inguinofemoral nodal areas
 48.2 ± 5 Gy (neoadjuvant)
 50 - 60 Gy (adjuvant)
 66 – 70 Gy (definitive)
 Brachytherapy
Technical aspects
Locally
advanced ST
III

50. Treatment volume
Organs at
risk

51. tumor
tumor
3D CRT IMRT
IMRT Reduce toxicity
rectum

52. VULVAR CANCER
Conclusions
Adjuvant RT should be offered if adverse
prognostic factors are present.
RT ± CHT after surgery is recommended
when there are 2 or more + groin lymph
nodes or 1 with ECI.
Adjuvant RT after surgery is recommended
if microscopic residual disease is present.
Early disease
(STI-STII)
Locally
advanced ST
III
Locally advanced
ST IV Neoadjuvant RT±CHT could make exenteration
unnecesary.
Definitive RT-CHT is still under investigation

53. Effective and safe oncological treatments
that do not impair long term functional
QoL
Thank you for your attention
Rising incidence of vulvar cancer in
younger and more active women