Monk Vulvar Cancer 1 positive SNL prime Barcelona 24.01.2014 Bradley J. Monk, M.D., F.A.C.S, F.A.C.O.G Professor and Director Division of Gynecologic Oncology Department of Obstetrics and Gynecology Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, a Dignity Health Member University of Arizona Cancer Center-Phoenix

1. Interactive Clinical Case
Treatment of Patients With One Positive
Sentinel Node: Perspectives on Surgical
Radicality and Adjuvant Therapy
Bradley J. Monk, M.D., F.A.C.S, F.A.C.O.G
Professor and Director
Division of Gynecologic Oncology
Department of Obstetrics and Gynecology
Creighton University School of Medicine at St. Joseph’s Hospital
and Medical Center, a Dignity Health Member
University of Arizona Cancer Center-Phoenix
Arizona USA

2. • 66-year-old patient, ECOG 1, hypertension,
no other concomitant disease
• Presents with “itching and burning”
at posterior part of the vulva, midline
• Gynecologic examination reveals
2 cm ulceration, suspicious of
vulvar cancer, groins clinically
and radiologically clear
• Punch biopsy confirms squamous
cell cancer, G3, infiltration >3 mm
Clinical Case:

3. 1. Wide radical local excision with inguinal
sentinel node dissection
2. Wide radical local excision with complete
inguinofemoral groin node dissection
3. Radical complete vulvectomy with inguinal
sentinel node dissection
4. Radical complete vulvectomy with complete
inguinofemoral groin node dissection
What would you recommend for
initial treatment ?

4. • 66-year-old patient, ECOG 1, hypertension,
no other concomitant disease
• Initial surgical treatment with wide radical
local excision and bilateral inguinal sentinel
node dissection (no frozen section performed)
• Squamous cell vulvar cancer G3, R0 (>10 mm)
pT1b (24 mm diameter, 4 mm infiltration),
pN1a (1/3 sn) left 4 mm intracapsular
metastasis
Clinical Case, cont

5. 1. No further treatment; regular follow-up
2. Complete ipsilateral inguinofemoral groin
node dissection
3. Complete bilateral inguinofemoral groin node
dissection
4. No further surgical therapy but adjuvant
treatment with other modality (radiotherapy,
chemotherapy, etc)
What would you recommend for
the next step of treatment ?

6. Risk of Additional Lymph Node Metastasis
in Patients With Positive Sentinel-node
van der Zee AG, et al. J Clin Oncol. 2008;26(6):884-889; Oonk MH, et al. Lancet Oncol. 2010;11(7):646-652.
Risk of non-sentinel metastasis
18%

7. 1. No further treatment, regular follow-up
2. Complete ipsilateral inguinofemoral groin
node dissection
3. Complete bilateral inguinofemoral groin node
dissection
4. No further surgical therapy but adjuvant
treatment with other modality (radiotherapy,
chemotherapy, etc)
What would you recommend for
the next step of treatment ?

8. Ipsi- or Bilateral Groin Dissection in
Patients With Positive Sentinel-Node
• 80% of pts had unilateral +SN, 20% bilateral
• 85% underwent additional complete LNE
• Thereof 70% bilateral and 30% ipsilateral
van der Zee AG, et al. J Clin Oncol. 2008;26(6):884-889; Oonk MH, et al. Lancet Oncol. 2010;11(7):646-652.

9. 1. No further treatment, regular follow-up
2. Complete ipsilateral inguinofemoral groin
node dissection
3. Complete bilateral inguinofemoral groin node
dissection
4. No further surgical therapy but adjuvant
treatment with other modality (radiotherapy,
chemotherapy etc.)
What would you recommend for
the next step of treatment ?

10. No Further Surgical Therapy After Single
Positive SNL and Immediate Adjuvant Therapy
• GROINSS-V II Study (Initital design)
• SN positive:
– No full lymphadenectomy
– Radiotherapy 50 Gy
– Stopping rules based on groin recurrence
rate of 4% with maximum increase of 6%
van der Zee ESGO Biennial Meeting 2013

11. No Further Surgical Therapy After Single
Positive SNL and Immediate Adjuvant Therapy
• GROINSS-V II Study
• Interim Analysis
van der Zee ESGO Biennial Meeting 2013
No Groin
Recurrences
Groin
Recurrence
Total
ITC and Micro-metastases 45 1 (2%) 46
Macro-metastases 36 9 (20%) 45
81 10 (11%) 91
ITC = Isolated Tumor Cell

12. No Further Surgical Therapy After Single
Positive SNL and Immediate Adjuvant Therapy
• GROINSS-V II Study
• Revised protoocl reopened Sept 2010
– Negative SN: Follow-up
– Positive SN, met < or = 2mm: RT (50Gy)
– Positive SN, met > 2mm: Lymphadenectomy
plus RT (50Gy)
– Extracapsular growth or >1 positive node: RT
(56Gy)
van der Zee ESGO Biennial Meeting 2013

13. 1. No further treatment, regular follow-up
2. Complete ipsilateral inguinofemoral groin
node dissection
3. Complete bilateral inguinofemoral groin node
dissection
4. No further surgical therapy but adjuvant
treatment with other modality (radiotherapy,
chemotherapy etc.)
What would you recommend for
the next step of treatment ?

14. • 66-year-old patient, ECOG 1, hypertension, no
other concomitant disease
• Surgical treatment with wide radical local
excision and bilateral inguinal sentinel node
dissection, secondary complete bilateral LND
• Squamous cell vulvar cancer G3, R0 (>10 mm)
pT1b (24 mm diameter, 4 mm infiltration),
pN1a (1/21) 4 mm intracapsular metastasis
Clinical Case, cont

15. What would you recommend for
adjuvant therapy?
1. No further treatment, regular follow-up
2. Adjuvant radiotherapy of groins
3. Adjuvant radiotherapy of groins and pelvis
4. Adjuvant chemoradiation of groins
5. Adjuvant chemoradiation of groins and pelvis

16. Prognostic Role of Lymph Node
Metastases in Vulvar Cancer
2-year PFS rate 80% N- vs 40% N+ 2-year OS rate 93% N- vs 63% N+
Mahner S, et al. J Clin Oncol. 2012;30(15S): Abstract 5007.

17. Woelber L, …Mahner S, et al. Int J Gynecol Cancer. 2012;22(3):503-508.
0.00
0.25
0.50
0.75
1.00
15 8 4 4 0 0 0 0 0
nodes = 3
13 11 6 3 2 1 0 0 0
nodes = 2
20 14 10 7 7 6 4 4 4
nodes = 1
108 101 79 60 46 37 27 17 11
nodes = 0
Number at risk
0 12 24 36 48 60 72 84 96
analysis time (months)
0
1
2
>2
>2
disease-free
survival
Prognostic Role of the Number of Groin
Node Metastases in Vulvar Cancer

18. Prognostic Role of the Size of Groin
Node Metastases in Vulvar Cancer
Oonk MH, et al. Lancet Oncol. 2010;11(7):646-652.

19. GOG 37
Surgery vs Radiotherapy
Homesley HD, et al. Obstet Gynecol. 1986;68(6):733-740; Kunos C, et al. Obstet Gynecol. 2009;114(3):537-546.

20. AGO CaRE-1: Adjuvant Radiotherapy
in Node-Positive Patients
Adjuvant radiotherapy is standard of care
for node-positive vulvar cancer
Mahner S, et al. J Clin Oncol. 2012;30(15S): Abstract 5007.

21. Open Questions on Adjuvant
Radiotherapy
• Threshold of number of positive nodes?
• Radiation fields?
• Chemoradiation?

22. GOG 37
Number of Positive Nodes?
• Is there a different
effect of radiotherapy
with regard to the
number of positive
nodes?
Homesley HD, et al. Obstet Gynecol. 1986;68(6):733-740; Kunos C, et al. Obstet Gynecol. 2009;114(3):537-546.

23. AGO CaRE-1
Number of Positive Nodes?
1 pos. LN 2 pos. LN
3 pos. LN > 3 pos. LN
Mahner S, et al. J Clin Oncol. 2012;30(15S): Abstract 5007.

24. SEER – Analysis
Treatment Effect in 1 Positive Node?
Parthasaraty A, et al. Gynecol Oncol. 2006;103(3):1095-1099.

25. Open Questions on Adjuvant
Radiotherapy
• Threshold of number of positive nodes?
– Prognosis deteriorates with 1 “macrometastasis”
– Positive effect of adjuvant therapy so far only
“proven” for patients with 2 or more positive nodes
– Positive effect assumed in case of extracapsular
spread
• Radiation fields?
• Chemoradiation?

26. • “Homesley GOG37 standard”
– Inguinal field + pelvic field
• However: risk of pelvic metastasis generally
low and particularly increases with 3 or more
positive inguinal nodes
– Inguinal field enough?
– Surgical assessment of pelvic nodes to determine
extent of radiation?
Radiation Fields for Adjuvant Therapy
in Node-Positive Vulvar Cancer
- 8 consecutive patients with positive groin nodes 1997-2004
- Laparoscopic pelvic lymphadenectomy
- no pelvic radiotherapy if nodes were negative
- radiation of the groins
→ interesting concept, warrants further study
Currently not safe for routine treatment
Klemm P, et al. Gynecol Oncol. 2005;99(1):101-105.

27. Open Questions on Adjuvant
Radiotherapy
• Threshold of number of positive nodes ?
– Prognosis deteriorates with 1 “macrometastasis”
– Positive effect of adjuvant therapy so far only
“proven” for patients with 2 or more positive nodes
– Positive effect assumed in case of extracapsular
spread
• Radiation fields?
– “Homesley Standard”: inguinofemoral + pelvic fields
• Chemoradiation ?

28. Clinical Trials on Adjuvant
Chemoradiation in Vulvar Cancer
• No phase III data
• 1 small and heterogenous series using
5-FU/Mitomycin
Han SC, et al. Int J Radiation Oncology Biol Phys. 2000;47(5):1235-1244.

29. P = ns P = ns
Subgroup of patients with adjuvant RCT
Han SC, et al. Int J Radiation Oncology Biol Phys. 2000;47(5):1235-1244.

30. Subgroup of patients with primary RCT
Han SC, et al. Int J Radiation Oncology Biol Phys. 2000;47(5):1235-1244.

31. Moore DH, et al. Gynecol Oncol. 2012;124(3):529-533.

32. AGO CaRE-2 Study
Patients with node-
positive primary
vulvar cancer
R
Adjuvant radiotherapy* plus
simultaneous chemotherapy
with 6 cycles cisplatinum 40
mg/m²
Adjuvant
radiotherapy*
* Radiotherapy fields per
institutional standards

33. What would you recommend for
adjuvant therapy?
1. No further treatment, regular follow-up
2. Adjuvant radiotherapy of groins
3. Adjuvant radiotherapy of groins and pelvis
4. Adjuvant chemoradiation of groins
5. Adjuvant chemoradiation of groins and pelvis

34. Conclusion: Treatment of Vulvar Cancer
With One Positive Sentinel Node
• Full groin dissection, ipsilateral or bilateral
• Prognosis impaired already with 1 intranodal
metastasis >2mm
• Adjuvant radiotherapy significantly improves outcome
in patients with 2 or more positive lymph nodes
• Surgical assessment of pelvic nodes to limit pelvic
radiotherapy to patients with pelvic metastases is an
interesting concept, but needs further studies
• Trial on adjuvant chemoradiation logical next step
to improve outcome of node-positive patients

35. Thank You
Bradley.monk@chw.edu