Block 3B - Gynecological Cancers (Vulva, Vaginal)

ONCOL 310 - Clinical Oncology II. University of Alberta

vulva cancer epidemiology

• ___% of all cancers diagnosed in women

• __ cases per 100 000

• ____ cases per 100 000 over age of 75

• incidence is higher in ______

• 1% of all cancers diagnosed in women

• 2.5 cases per 100 000

• 15.5 cases per 100 000 over age of 75

• incidence is higher in white women than black

what is the exact cause of vulva cancer

unknown

etiological factors of vulva cancer

• increasing age, HPV, smoking, weakened immune system, precancerous conditions, skin conditions of vulva

what is the precursor condition to vulvar cancer

vulvar intraepithelial neoplasia (VIN)

what are the two most common histologies of vulva cancer

• 90% SCC

• 5% melanoma

  • others indlude adenocarcinoma, sarcomas, basal cell carcinoma

what are the two most common sites of vulva cancer

labia majora and minora

what features of vulva cancer are associated with nodal metastasis

tumor thickness, histologic grade, depth of invasion, location of tumor, tumor size

where can vulva cancer spread locally?

Along the vulva and perineum, Urethra, Vagina, Anus , Bladder, Rectum

what are the two primary LN involved in vulva cancer

superficial inguinal nodes and internal iliac nodes

what are the three most common metastatic sites of vulva cancer

liver, lung, bone

• rare, later, and will occur after LN involvement

how will vulva cancer present clinically?

pruritus, soreness, burning, tingling sensation or pain in the vulva

Wart-like growths, thickened skin, or lumps on the vulva or on either side of the opening to the vagina

Raw patches or ulcers, fluid leaking out from growth

Changes in the appearance of a mole on the vulva

Unusual bleeding or discharge that is not menstruation

Pain during urination or sexual intercourse

One or more swollen or hard lymph nodes in the groin

what is done during a physical exam when diagnosing vulva cancer

Feel uterus, ovaries, cervix, and vagina for anything irregular. Doctor will also look at vagina and cervix and may do a Pap test and an HPV test.

what biopsy is done if abnormal area is small? large area?

small area = excisional biopsy

large area = punch biopsy

what imaging tests can be done to diagnose vulva cancer

Chest X-ray

CT

MRI

PET

Ultrasound +/- FNAC (fine-needle aspiration cytology)

Referral to gynecologic oncologist

what is the most important prognostic indicator of vulva cancer

stage

• earlier = more favourable

other prognostic indicators of vulva cancer

Tumour size , Tumour volume, Local extent

Pathology

• SCC most favourable

Grade

Spread to lymph nodes

Location of the tumour

Symptoms

• Women who present with symptoms = less favourable

Age & General health (younger women better outlook than >60 yrs + good health)

Hysterectomy status

• Studies have shown an advantage for earlier hysterectomy

Stage I Vulva Cancer

Tumor confined to the vulva

• IA—Tumor size ≤ 2 cm and stromal invasion ≤ 1 mm *

• IB—Tumor size > 2 cm or stromal invasion > 1 mm *

Stage II vulva cancer

Tumor of any size with extension to lower one-third of the urethra, lower one-third of the vagina, lower one-third of the anus with negative nodes

Stage III vulva cancer

Tumor of any size with extension to the upper part of adjacent perineal structures or with any number of nonfixed, nonulcerated lymph nodes

• IIIA—Tumor of any size with disease extension to upper two-thirds of the urethra, upper two-thirds of the vagina, bladder mucosa, rectal mucosa, or regional lymph node metastases ≤ 5 mm

• IIIB—Regional ** lymph node metastases > 5 mm

• IIIC—Regional ** lymph node metastases with extracapsular spread

Stage IV vulva cancer

Tumor of any size fixed to the bone or fixed, ulcerated lymph node metastases, or distant metastases

• IVA—Disease fixed to the pelvic bone or fixed or ulcerated regional ** lymph node metastases

• IVB—Distant metastases

what is the primary treatment of vulva cancer

primarily surgical

• based on staging and risk of nodal involvement

treatment of stage I-II vulvar cancer

conservative surgery

treatment of stage III-IV vulvar cancer

RT or chemoRT

what surgery is used to treat early stage lateral vulvar tumors?

Radical or hemivulvectomy +/- unilateral or bilateral lymphadenectomy

what surgery is used to treat early stage central vulvar tumors?

Radical vulvectomy + bilateral lymphadenectomy +/- reconstruction

what is added to surgery if the early stage vulva cancer has close margins or positive LNs

adjuvent RT

what surgery is done for stage III and IV vulvar cancer

fairly individualized

• +/- vulvectomy +/- bilateral or unilateral lymphadenectomy +/- >1 LN MET…

list some of the rist factors that RT will be added to surgery for?

“+” margins

Lymphovascular invasion

“-” BUT close tumor margins (< 8 mm)

Tumor size

Depth of invasion > 1 mm

Spray or diffuse pattern of invasion

Nodal involvement (“+” sentinel LN, “+” LN’s post-inguinofemoral node dissection, > 1 metastatic LN &/or presence of extracapsular LN)

Whatis the primary treatment for Stage III-IV vulva cancer who is not a surgical candidate

radiation therapy ± concurrent chemo

Stage III-IV vulvar cancer RT

• energy

• technique

• treatment site

• D/F

• use of bolus

6 MV (or 15 if seperation > 24 cm)

POP

RT to primary site + pelvis + inguinal nodes

50 Gy / 25-28 fractions

eliminate cold spot on the vulva + inguinal nodes

what are the sup, inf, and lat borders for RT to vulva cancer

Sup = L4/L5 (common iliacs) or L5/S1 (int/ext iliacs)

inf = 2-3 cm below vulvar marker (entire vulva)

lat = 1.5 cm lat to pelvic brim (to invlcue inguinal nodes)

when would PORT be used for vulva cancer and what is the typical D/F

PORT is used to local recurrences in tumors with “+” margins, tumor > 4cm OR depth of invasion >7 mm

• D/F = 45-50 Gy / 20-25 fr

what is the typical set-up for RT for vulva cancer patients

supine, head on 10 cm sponge, hands on chest, ‘frog leg’ position for larger patients

Historical Phase I RT treatment of vulva cancer

• technique

• D/F

equally weighted POP (wider AP and narrow PA field)

• AP treats pelvic and inguinal area, PA treats pelvis only)

45-60 Gy / 2 fractions

Historical Phase II RT treatment of vulva cancer

• technique

• depth

electron boost to inguinal nodes (direct abuttment)

depth to inguinal nodes = 3-4 cm ± bolus

modern vulva cancer RT treatments use IMRT/VMAT to spare OARs. What OARs are spared?

IMRT improves tumor coverage while sparing femoral necks, small bowel, rectum, bladder, skin

vulvar cancer modern treatment

• energy

• technique

• D/F

6 MV

VMAT with 1 CW and 1 CCW arc

54 Gy / 30 fractions

what are the two main chemotherapies used in treating vulvar cancer

5-FU (alone or with cisplatin or mitomycin-c)

platinum based (alone or with 5-FU)

• cisplatin, carboplatin, paclitaxel, erlotinib

what are some vulva cancer RT related acute side effects

mucocutaneous reaction in the vulva, perineum, and inguinal folds

Fatigue

Erythema, dry desquamation, moist desquamation

Diarrhea

Radiation cystitis

Vaginal narrowing, dryness and painful intercourse

what are some vulva cancer surgery related acute side effects

wound infection

hematomas

seromas

hemorrhage

deep vein thrombosis

pulmonary embolism

osteitis pubis

loss of sensory perception in the anterior aspect of the thigh secondary to femoral nerve injury

what are some vulva cancer RT related chronic side effects

telangiectasis

atrophy of the skin

dryness of the mucosa of the vagina and vulva

narrowing of the vaginal introitus

avascular necrosis

what are some vulva cancer surgery related chronic side effects

lymphedema

chronic cellulitis of the inguinal areas

stenosis of the introitus

femoral hernias

rectovaginal or rectoperineal fistulas

sexual dysfunction

overall 5 year survival of vulva cancer

71%

most malignancies of the vagina are due to…

invasion from nearby tumors (cervix and vulva)

vaginal cancer epidemiology

• % of all gynecological malignancies

• age of peak incidence

• why increased incidence in younger women

• race effects

• 1-2% of all gynecological malignancies

• mean age is 65

• increased incidence in younger women due to HPV infections

• incidence higher in african american women, lowest for asian

what is the most common cause of vaginal cancer

HPV

other etiological risk factors of vaginal cancer

Previous cervical cancer

In-utero exposure to diethylstilboestrol (DES)

Previous hysterectomy

Smoking - 2x risk of vaginal cancer

Older than 60 years old

Having HIV

what is the most common pathology of vaginal cancer

squamous cell carcinoma - cells lining the inside of the vagina

what pathology of vaginal cancer is most likely to spread

adenocarcinoma - glandular cells in the lining of the vagina

what is the precurso lesion to SCC of the vagina

vaginal intraepithelial neoplasia (VAIN)

• VAIN 1: low grade, changes limited to upper ⅓ of the epithelium

• VAIN 2: changes in lower ⅔ of the epithelium

• VAIN 3: changes involving full thickness of epithelium, carcinoma in situ

vaginal cancer most commonly involves the _____ of the vaginal canal

superior 1/3 of vaginal canal

• lateral walls less involved

anterior wall vaginal lesions infiltrate ____

posterior wall lesios infiltrate _____

anterior wall: infiltrates vesicovaginal septum or urethra

posterior wall: infiltrates rectovaginal septum or rectal mucosa

advanced vaginal cancer will infiltrate ….

parametrium, paracolpi tissues, urogenital diaphragm, levator ani muscles, pelvic fascia, pelvic sidewall

what are the three most common sites of vaginal cancer distant mets

lung, liver, bone

what are some clinical presentations of vaginal cancer

• Abnormal bleeding from the vagina - post-coital, post-menopausal or between menstrual periods

• Vaginal discharge that smells foul or has blood in it

• Painful sexual intercourse

• Lump in the vagina that can be felt

• Constant pain in the pelvis, back, legs and perineum 

• Change in bladder habits - pain, burning or trouble urinating, the need to urinate often, blood in the urine and urgent need to urinate

• Change in bowel habits - blood in the stool, constipation and painful bowel movements

• Swelling in the legs or groin

in a physical exam that assists in diagnosing vaginal cancer, what is done?

• Pelvic exam (DR/vaginal exam if suspected spread into rectum) and Pap test to check for abnormalities that may indicate vaginal cancer

  • Based on those findings, your doctor may conduct other procedures to determine whether you have vaginal cancer

what is the gold standard for diagnosing vaginal cancer

biopsy

what imaging tests can be done to diagnose vaginal cancer

colposcopy, CXR, CT, MRI, FDG-PET

what can imaging cancers be used for after diagnosis of vaginal cancer

to learn more about the cancer and see if it has spread

what is the most prognostic indicator of vaginal cancer

stage

• earlier stage = more favorable

other prognostic indicators of vaginal cancer

• Tumour size 

• Tumour volume

• Local extent

• Pathology

  • SCC most favourable 

• Grade

• Spread to lymph nodes

• Location of the tumour

  • middle and lower ⅓ of vagina or those on the back wall have a less favourable prognosis

• Symptoms

  • women who present with symptoms = less favourable

•  Age & General health

  • younger women better outlook than >60 yrs + good health

  •  Hysterectomy status: studies have shown an advantage for earlier hysterectomy

what sites can vaginal cancer spread locally to?

urethra, bladder, cervix, rectum, parametrial tissues, and paracolpial tissues (vascular and connective tissue)

what are the three most involved LNs in vaginal cancer

paracervical nodes, internal iliac nodes, superficial inguinal nodes

vaginal cancer blood spread will occur after …

LN involvement

• rare and later

Stage 0 vaginal cancer

carcinoma in situ

stage I vaginal cancer

tumor confined to the vagina

stage II vaginal cancer

invasion o the paravaginal tssiues but no extension beyond pelvic side walls

stage III vaginal cancer

extension to pelvic side walls

stage IV vaginal cancer

spread beyond the true pelvis

• stage IVa: invasion of bladder/rectal mucosa and/or extension beyond the true pelvis

• stage IVb: distant metastatic disease

Vaginal cancer TNM staging - T

• primary tumor (T)TX - primary tumor cannot be assessed

• T0 - no evidence of primary tumor

• T1 - tumor confined to vagina

  • T1a - tumor confined to vagina, measuring ≤ 2 cm

  • T1b - tumor confined to vagina, measuring > 2 cm

• T2 - tumor invading paravaginal tissues but not to pelvic sidewall

  • T2a - tumor invading paravaginal tissues but not to pelvic sidewall, measuring ≤ 2 cm

  • T2b - tumor invading paravaginal tissues but not to pelvic sidewall, measuring > 2 cm

• T3 - tumor extending to pelvic sidewall (defined as muscle, fascia, neurovascular structures, or skeletal portions of bony pelvis; on rectal examination, there is no cancer-free space between the tumor and pelvic sidewall)

• T4 - tumor invading mucosa of bladder or rectum and/or extending beyond true pelvis (bullous edema not sufficient evidence to classify tumor as T4)

Vaginal cancer TNM staging - N

• NX - regional lymph nodes cannot be assessed

• N0 - no regional lymph node metastasis

• N0(i+) - isolated tumor cells in regional lymph node(s) ≤ 0.2 mm

• N1 - pelvic or inguinal lymph node metastasis

Vaginal cancer TNM staging - M

• M0 - no distant metastasis (no pathologic M0; use clinical M to complete stage group)

• M1 - distant metastasis

what is the treatment of vaginal cancer based on?

based on clinical staging and risk of nodal involvement

what are the two goals of treatment of vaginal cancer

• treat to cure

• vaginal preservation of anatomy and function

what is the most common treatment of vaginal cancer

radiation therapy

what is the primary treatment of vaginal cancer with unfavourable factors?

neoadjuvent chemo + radical surgery

what are some unfavourable factors that chemo and sx would be used to treat vaginal cancer

cervix primary site, large lesion, extensive disease

what is the treatment of small superficial stage I and minimal stage II vaginal cancer

brachytherapy (interstitial and intracavitary)

what is the treatment of large stage I and II vaginal cancer

EBRT + intracavitary brachytherapy

what surgery may be used to treat stage I and II vaginal cancer and why?

radical hysterctomy + lymphadenectomy

• preserve ovarian and sexual function

what is the primary treatment for advanced stage vaginal cancer

definitvie RT

what is the treatment plan for stage III and IVA vaginal cancer

interstitial + intracavitary brachy + EBRT

what surgery can be used for stage IVA vaginal cancer

Primary pelvic exenteration + pelvic lymphadenectomy OR neoadjuvant chemoRT

what is the treatment plan for stage IVB vaginal cancer

palliative EBRT and concurrent CT

what chemotherapies are used in the treatment plans of vaginal cancer

cistplatin or 5FU

overal chemo adds minimal 5 year survival benefit, but there seems to be increased benefit in stages ….

II-IV

why may surgery be chosen for early stage vaginal cancer (I-II: tumor limited to vaginal mucosa)

• preserve ovarian and sexual function

• eliminate risk for radiation-induced malignancies

what surgical procedures (3) can be used for disease in the upper vagina for patients with an intact uterus

radical hysterectomy

vaginectomy with 1 cm dx-free margins

pelvic lymphadenectomy

what surgical procedure can be used for disease in the lower vagina

Radical wide local excision with 1 cm margin + bilateral groin node dissection

what surgical procedure can be used for stage IV disease with vesical or rectal-vaginal fistulas

bilateral inguinofemoral lymphadenectomy

what hysterctomies performed open or laparoscopically?

laparoscopically

what is the primary benefit of doing EBRT and brachy therapy?

organ preservation

vaginal cancer EBRT

• energy

• technique

• field size

• D/F

• accessories

• 15 MV (6 MV potentially for diff field weight)

• AP/PA (unequal weighting) or 4FB

• 15×15 cm or 15 × 18 cm

• 45-50.4 Gy / 25-28 f

• 2 cm bolus for clinically palpable LNs

what should the EBRT fields include?

Encompass entire vagina, paravaginal area to pelvic sidewalls, LN’s at risk

• distal common iliac, internal iliac, external iliac, obturator, presacral (+ inguinals if distal 1/3 to ½ of vagina)

what are two options for the boost added to EBRT for vaginal cancer? what does should tumor receive after the boost?

brachy or IMRT

• boost primary tumor to 70-80 Gy

what are the sup, inf, lat borders for the AP/PA fields of EBRT treatment of early stage vaginal cancer

sup = L5/S1

inf = bottom of obturator foramen

• for lower 1/3 vaginal lesions we extend length inferiorly to include inguinal nodes

lat = 1.5 cm lat of pelvic brim

what are the ant and post fields for the lat fields of EBRT treatment of early stage vaginal cancer?

ant = mid pubic symphysis

post = S2-S3

brachytherapy is indicated for all patients with ….

primary or recurrent vaginal cancer

Brachytherapy vaginal cancer treatment

• Dose rates (2)

• source

• D/F for intracavitary (<0.5 cm thick)

• D/F for interstitial (> 0.5 cm thick)

• HDR or PDR

• Ir-192

• 60-65 Gy / 3 fractions (10-20 mins long)

• 70-85 Gy / 3 fractions (10-20 mins long)

give an example typical dose prescription for a EBRT + brachy boost for vaginal cancer

45 Gy in 25 fractions EBRT and 5.5 Gy x 5 fractions HDR brachytherapy with CTV D90 = 79.8 Gy