Treatment/Prognosis Flashcards
What is the Tx for vulvar CIS or VIN?
Pts with vulvar CIS or VIN can be treated with superficial local excision. If the labia minora or clitoris is involved, consider laser ablation.
How should the primary of a pt with FIGO stage I or II vulvar cancer be treated?
In a pt with stage I or II vulvar cancer, the primary can be resected via a WLE, which includes resection of the tumor + a gross 1.0-cm margin of normal tissue around it. WLE has the same LR as radical vulvectomy for stage I and II vulvar carcinomas. (Hacker NF et al., Cancer 1993)
Which large retrospective study failed to confirm significance of wide (>8 mm) margins for resected T1–2 lesions?
AGO-CaRE-1 (Arbeitsgemeinschaft Gyn↑kologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer): At median f/u of 35 mos, vulvar recurrence rates were 12.6% in pts with a margin <8 mm and 10.2% in pts with a margin >8 mm (NSS). (Woelber L et al., Eur J Cancer 2016)
What is the next step if margins are positive following surgical resection of vulvar cancer?
Re-excise if possible; otherwise, give adj RT. Adj RT is associated with an increase in LC and survival. (Chapman BV et al., Int J Radiat Oncol Biol Phys 2017; Faul CM et al., IJROBP 1997)
What are the guidelines for LN assessment for stage I–II vulvar carcinoma?
Nodal assessment may be excluded if <1 mm depth invasion and cN0
All other cN0: SLNB or inguinal LND
SLND established for unifocal stage I–II carcinoma, <4 cm, cN0
If ITC or micromets (>0.2 mm–2.0 mm) → RT or LND
If macromets (>2.0 mm) → full LND → RT
Strongly consider adding concurrent chemo for LN positive (Gill et al., Gynecol Oncol 2015)
Contralat assessment if <2 cm from midline (<3% risk)
If clinically LN positive → Inguinofemoral LND
Adequate Inguinal LND
>10 nodes each side
Superficial and deep assessment needed
LN+ to total LN removed ratio on each size needs to be ≤20% (GOG 37)
LND increases risk of lymphedema to ∼25% (GROINSS-V)
Attempts to lower morbidity by superficial dissection alone lead to higher rates of recurrence (GOG 74)
In which vulvar cancer pts is adj RT to the bilat groin and pelvis indicated? What RCTs explored this question?
Adj RT to the bilat groin and pelvis is recommended in pts with ≥2 +LN, >20% nodal positivity, a single node >5 mm, presence of ECE, or pts with SLN positive yet no nodal dissection was performed.
In GOG 37, 114 pts s/p radical vulvectomy + bilat inguinal LND. If LN+ were randomized to pelvic node dissection or pelvic and groin RT. The dose was 45–50 Gy.
Updated Analysis showed pelvic and groin RT group had a higher 6-yr RFS (48→59%) and CSS (49→71%). Subset analysis showed RT benefitted pts with clinical suspected or fixed ulcerated groin nodes or ≥2 groin LN. A ratio of >20% ipsi positive groin node/groin node dissected was associated with a decrease in cancer-related mortality, relapse, and contralat LN mets, but had a better OS in the RT group. The initial 2-yr OS benefit to RT (54→68%) was not significant at 6 yr (41 vs. 51%, p = NS). The benefit of RT was likely d/t the decrease in groin recurrence (24→5%), as recurrence in the pelvis (2% vs. 5%), vulvar (7% vs. 8%), or DM (15% vs. 16%) were the same.
(Kunos C et al., Obstet Gynecol 2009)
(Homesley HD et al., Obstet Gynecol 1986)
Also AGO-CaRE-1 (Arbeitsgemeinschaft Gyn↑kologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer) was a retrospective study evaluating 1,249 vulvar pts of which 447 (36%) were found to have positive pathologic groin nodes. 55% (244/447) of node positive pts rcvd adj Tx of which 84% was adj RT and 14% was adj CRT. Part of the analysis evaluated pts treated with or without adj RT or CRT. Adj Tx was associated with an increase in 3-yr PFS (26→40%). However, on subset analysis, the benefit was only for those with ≥2 positive LNs. (Mahner S et al., J Natl Cancer Inst 2015)
Is there data specifically supporting concurrent chemo being added to adj RT for LN positive pts?
Yes. A National Cancer Data Base (NCDB) analysis on pathologic inguinal LN pts treated with adj RT was conducted to determine the impact of the addition of adj chemo. The addition of adj chemo was associated with an increase in unadjusted MS (30→44 mos) and on adjusted propensity score matching, a 38% reduction in risk of death. (Gill BS et al., Gynecol Oncol 2015)
In pts with N0 vulvar cancer, does groin RT eliminate the need for inguinal LND? What RCT explored this question?
The need for inguinal node dissection in N0 vulvar cancer prior to groin RT is controversial. In GOG 88, 58 pts with cN0 vulvar cancer s/p radical vulvectomy were randomized to bilat inguinofemoral and pelvic LND (+nodes rcvd RT) vs. bilat groin-only EBRT (50 Gy). LR, PFS, and OS favored the LND arm. (Stehman FB et al., Cancer 1992)
But there are major criticisms of GOG 88
a. CT was not used for staging.
b. 50 Gy is not adequate for pts with gross nodes evident by CT.
c. Pts were treated with electron fields prescribed to a depth of 3 cm, which may not adequately cover the inguinal/femoral nodal regions. Koh et al. reported the avg femoral vessel depth ranges from 2 to 18 cm. He also reported on 5 pts who recurred after prophylactic RT in GOG 88 and showed all rcvd potential doses of <47 Gy and 3 pts rcvd more than 30% under dosing. (Koh WJ et al., Int J Radiat Oncol Biol Phys 1993)
What are the indications for adj RT to the primary site after surgical management?
The relative indications for adj RT to the primary site are based upon Heaps factors.
+Margins
Close margins (<8 mm fixed specimen or <1 cm by frozen)
LVSI
2+ Heaps factors (thickness >2.5 mm, >1 cm deep, LVSI, infiltrative/mixed growth pattern)
(Heaps JM et al., Gynecol Oncol 1990)
The most important risk for local recurrence is +margin. Salvage surgery leads to a lot of morbidity.
What is the Tx approach for pts with stages III–IV vulvar cancer?
Tx options for stages III–IV vulvar cancer:
Surgery (if –margins can be achieved) + RT(+/– chemo)
Neoadj CRT (phase II) → surgery; for those initially unresectable
Definitive CRT
What studies support neoadj CRT in initially unresectable vulvar cancer?
GOG 205 was a phase II trial of 58 pts with T3–4 vulvar SCC unable to obtain radical vulvectomy s/p CRT with 40 mg/m2 of weekly cisplatin. RT was 57.6 Gy @ 1.8 Gy/daily with a CD after 45 Gy to gross Dz + margin with no Tx break. cCR was 64% and pCR rate was 50% (22% with cCR still had residual Dz). When compared to prior GOG 101, the cCR (48→64%) and pCR (31→50%) was higher. (Moore DH et al., Gynecol Oncol 2012)
GOG 101 was a phase II study of 73 pts with unresectable vulvar cancer given concurrent cisplatin/5-FU + RT. RT was bid to 47.6 Gy with planned Tx break. 97% of pts were converted to resectable Dz. (Moore DH et al., IJROBP 1998)
Estimate the 5-yr OS by FIGO stage.
5-yr estimated OS by FIGO stage:
Stage I: 90%
Stage II: 81%
Stage III: 68%
Stage IV: 20%
(Gonzalez-Bosquet J et al., Gyn Oncol 2005)
What are the commonly used neoadj, adj and definitive RT doses for vulvar cancer?
Neoadj RT doses
a. Nodal regions and vulva: 45.0–50.4 Gy
b. High-risk sites (gross Dz): 55.8–59.4 Gy
Adj RT doses
a. –Margin, +LVSI: 50.4–54.0 Gy
b. Close or margin positive: 56.0–59.4 Gy
c. Inguinal LN positive regions: 50.4–54.0 Gy
d. ECE regions: 56.0–59.4 Gy
Definitive RT doses
a. Unresectable Dz: 66–70 Gy to primary site with concurrent weekly cisplatin +/– 5-FU
b. Gross nodal Dz: 56–59.4 Gy
(Chapman BV et al., Int J Radiat Oncol Biol Phys 2017)
(Viswanathan AN et al., Gynecol Oncol 2013)
What are the anatomic boundaries of the inguinal LNs?
The key point to remember is that the groin nodes are usually very medial to the inguinal–femoral vessels. Therefore, the classic 7 mm–1 cm margin around the vessels, commonly done for pelvic LN contouring is inaccurate.
Radial boundaries: Sartorius muscle, Rectus Femoris, Iliopsoas, lat edge of pectinus or medial edge of abductor longus
Cranially: Follow the external iliac transitioning to the inguinal vessels
Caudal: Either the inf trochanter or 2 cm below the junction of the great saphenous and the common femoral vein
(Beriwal et al., Pract Radiat Oncol 2012)
(Gaffney DK et al., Int J Radiat Oncol Biol Phys 2016)
What are the ongoing trials for vulvar carcinoma pts?
GOG 279 is a phase II trial evaluating the addition of concurrent gemcitabine and cisplatin to IMRT. Pts with primary locally advanced (T2/3, N0–3, M0) unresectable by standard radical vulvectomy rcv concurrent weekly gemcitabine and cisplatin with IMRT. Pts rcv a core Bx to vulvar or if gross Dz present, surgical removal of gross Dz at primary and/or groin LNs, within 6–8 wks after completion of therapy. Primary outcome is pCR. Secondary outcomes are cCR, vulvar-PFS, groin-PFS, and toxicity.
GOG 270/GROINSS-V II
a. T<4 cm w/ DOI>1 mm; cN0
b. Originally: SLNB– → observation, SLNB+ → RT
c. Pts with macromets: 20% risk of additional +LNs vs. 2% with micromets
i. Crossed prespecified safety border in macromets cohort
ii. Amended: SLNB+ (<2 mm) → RT; if >2 mm, LND → RT +/– chemo
