Campbell Penile CA Review + NCCN Penile 2021

Question 1

Penile lesion NOT associated with viral infection

Answer 1

BXO

Associated with viruses:
HPV infection:
Condyloma
Bowenoid
Erythroplasia of Queyrat

HHV-8:
Kaposi sarcoma

Question 2

Infection associated with cervical dysplasia: ___

Answer 2

HPV infection: principal etiologic agent in cervical cancer

Question 3

Major difference between Bowen disease vs. Erythroplasia of Queyrat

Answer 3

Location!
Queyrat: Glans penis or prepuce

Bowen disease: penile shaft skin, perineal, genitalia

Question 4

Kaposi sarcoma etiologic agent

Answer 4

Human Herpesvirus 8

Question 5

Where do penile cancers most commonly arise?

Answer 5

Glans

Glans (48%)
Prepuce (21%)

Question 6

Risk factors for development of SCCA of the penis: ___

Answer 6

Smoking
HPV infection
Phimosis
Tobacco chewing

Campbell: Gonorrhea NOT a risk factor
NCCN: STD = risk factor

Question 7

Preventive strategies to decrease incidence of penile cancer: ___

Answer 7

HPV vaccination
Daily genital hygiene
Avoid tobacco
Circumcision before puberty

CampbellReview: Adult circumcision appears to offer little or no protection from subsequent development of the disease.

Question 8

Campbell review TRUE statements:

Answer 8

Cancer may develop anywehere on the penis
Phimosis may obscure the nature of the lesion
Penetration of Buck fascia and tunica albuginea –> permits invasion of the vascular corpora
Cancer cells reach contralateral inguinal region –> lymphatic cross communications at the base of the penis

Question 9

Penile cancer initial spread: ___

Answer 9

Metastasis initially involves inguinal lymph nodes above the fascia lata

The lymphatics of the prepuce form a connecting network that joins with the lymphatics from the skin of the shaft. These tributaries drain into the superficial inguinal nodes (the nodes external to the fascia lata)

Question 10

Hypercalcemia in penile cancer

Answer 10

Parathyroid hormone-like substances released from the tumor. Parathyroid hormone and related substances may be produced by both tumor and metastases that activate osteoclastic bone resorption.

Question 11

Imaging with 100% sensitivity for cavernosal invasion: ___

Answer 11

Ultrasonography

Question 12

Stage T2 tumors: ___

Answer 12

Invade the corpus spongiosum but not the cavernosum

Question 13

Strongest prognostic factor for survival of penile cancer: ___

Answer 13

The extent of lymph node metastasis.

The presence and extent of metastasis to the inguinal region are the most important prognostic factors for survival in patients with squamous penile cancer.

Question 14

Criteria for curative resection (> 70% 5-yr survival) in patients treated for LN mets: ___

Answer 14

no more than two positive inguinal lymph nodes.
no positive pelvic lymph nodes.
absence of extranodal extension of cancer.
unilateral metastasis.

LN > 4 cm is often associated with extranodal extension of cancer

Question 15

Surgical staging is strongly considered in: ___

Answer 15

palpable adenopathy.
stage T1b or greater primary tumor.
presence of vascular invasion in primary tumor.
presence of predominantly high-grade cancer in primary
tumor.

Question 16

Inguinal procedures for non-palpable adenopathy: ___

Answer 16

(1) dynamic sentinel node biopsy,
(2) superficial dissection,
(3) modified complete dissections, and
(4) laparoscopic and robotic approaches.

Question 17

Adjuvant or neoadjuvant chemotherapy for the following: ___

Answer 17

single pelvic nodal metastasis
extranodal extension of cancer
fixed inguinal masses
single 6-cm inguinal lymph node

Question 18

Histology of majority of penile cancers: ___

Answer 18

SCCA

** The majority of tumors of the penis are squamous cell carcinomas demonstrating keratinization, epithelial pearl formation, and various degrees of mitotic activity.

Question 19

Chemotherapeutic agent with significant pulmonary toxicity

Answer 19

Bleomycin

** Response rates of bleomycin, whether as a single agent or in combination with other agents, has not been shown to be superior to cisplatin alone, but has been associated with significant pulmonary toxicity and death in several series of patients treated for metastatic penile cancer.

Question 20

Primary penile melanoma is rare because: ___

Answer 20

Penile skin is protected from exposure to the sun.

Melanoma and basal cell carcinoma rarely occur on the penis, presumably because the organ’s skin is protected from exposure to the sun.

Question 21

Lymphomatous infiltration of the penis is most likely due to: ___

Answer 21

Diffuse disease

** When lymphomatous infiltration of the penis is diagnosed, a thorough search for systemic disease is necessary.

Question 22

Most frequent sign of metastatic involvement of the penis: ___

Answer 22

Priapism

** The most frequent sign of penile metastasis is priapism; penile swelling, nodularity, and ulceration have also been reported.

Question 23

Bushcke-Lowenstein tumor vs. condyloma acuminatum

Answer 23

The Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue.

Buschke-Löwenstein tumor displaces, INVADES, and destroys adjacent structures by compression. Aside from this unrestrained local growth, it demonstrates no signs of malignant change on histologic examination and does not metastasize.

Question 24

Treatment for small lesions of erythroplasia of Queyrat

Answer 24

Topical 5% 5-FU

Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser

Local excision

Imiquimod

Question 25

Standard treatment of choice for condyloma

Answer 25

Imiquimod cream

Question 26

3 types of penile Tis

Answer 26

Bowenoid papulosis
Bowen disease
Erythroplasia of Queyrat

Question 27

Initial evaluation of suspicious penile lesion:

Answer 27

H&P
Risk factors
◊ Balanitis, chronic inflammation, penile trauma, lack of neonatal circumcision, tobacco use,
lichen sclerosus, poor hygiene, sexually transmitted disease
Lesion characteristics
◊ Diameter, location, number of
lesions, morphology (papillary, nodular, ulcerous, or flat), relationship to other structures (submucosal, corpora spongiosa, cavernosa, and/or urethra)
• Histologic diagnosis
Punch, excisional, or incisional
biopsy
Assess HPV status

Question 28

PRIMARY TREATMENT

Tis or Ta

Answer 28

Topical therapyb
or b
Wide local excision
or b
Laser therapy (category 2B) or
Complete glansectomy
or
Mohs surgery in select cases (category 2B)

Question 29

PRIMARY TREATMENT
T1
Grade 1-2

Answer 29

Wide local excisionb
or c,d Partial penectomy
or b Glansectomy in select cases or b Mohs surgery in select cases or b
Laser therapy or d Radiotherapy

Question 30

PRIMARY TREATMENT
T1
Grade 3-4

Answer 30

Wide local excisionb
or c,d Partial penectomy
or c,d Total penectomy
or
Radiotherapy
or Chemoradiotherapy

Question 31

PRIMARY TREATMENT

T2 or greater

Answer 31

Partial penectomyc,d

or c,d Total penectomy or RT or chemoRT

Question 32

NON-PALPABLE INGUINAL LNs

Answer 32

LOW RISK:
Surveillance

INTERMEDIATE/HIGH RISK
T1b
Any T2 or greater
-- chest CT and abdominal/pelvic CT
-- ILND or DSNB

Question 33

PALPABLE INGUINAL LNs, NON-BULKY
after Chest CT + abdominal/pelvic CT

Unilateral LN <4 cm mobile

Answer 33

Low-risk primary lesion –> percutaneous LNB –> if negative, excisional biopsy or surveillance; if positive, ILND, consider NAC then ILND

High-risk primary lesion: ILND or consider NAC then ILND –> if pN1, surveillance;
if pN2-3:
PLND± adjuvant RT or chemotherapy or chemoRT
or chemoRT
or
chemotherapy

Question 34

PALPABLE INGUINAL LNs,
BULKY
Unilateral lymph nodes
≥4 cm (mobile) –> percutaneous LN biopsy

Answer 34

Cisplatin-based neoadjuvant chemotherapy followed by ILND c (preferred), consider PLND or c
ILND (preferred), consider PLNDc (in patients not eligible for cisplatin-based chemotherapy)

if 0-1 positive nodes with viable disease –> surveillance
if =>2 positive nodes or extranodal extension –> adjuvant chemotherapy and/or if pelvic nodes positive, adjuvant RT or chemoRT

OR

RT

OR

Chemoradiotherapy

Question 35

PALPABLE INGUINAL LNs BULKY

Unilateral lymph nodes (fixed)n or bilateral lymph nodes (fixed or mobile) –> percutaneous LN biopsy

Answer 35

Negative biospsy ==> excisional biopsy –> negative, surveillance; if positive –> NAC –> if responsive: ILND and PLND, or RT or chemoRT

Positive biopsy –> NAC –> then if responsive –> ILND and PLND or RT or chemoRT

If not eligible for NAC –> ILND and PLND or RT or chemoRT

then: surveillance

Question 36

ENLARGED PELVIC LNs

Percutaneous biopsy if technically feasible

Answer 36

Negative biopsy –> manage according to LN status

Positive biopsy:
SURGICAL candidate –> NAC –> imaging of chest/pelvis/abdomen –> stable or clinical response –> consolidation surgery
Disease progression or non-resectable –> XXX

NON-SURGICAL candidate –> chemoRT –> surveillance

Question 37

SURVEILLANCE SCHEDULE
Anatomic Site
Primary lesion

Answer 37

Initial treatment: 
• Topical therapy
• Laser therapy
• Radiation/Chemoradiation therapy • Wide local excision
• Glansectomy
• Mohs surgery
==> Clinical exam:
years 1–2, every 3 mo then years 3–5, every 6 mo then years 5–10, every 12 mo

• Partial penectomy • Total penectomy
==> Clinical exam
years 1–2, every 6 mo then years 3–5, every 12 mo

Question 38

LNs

Answer 38

Nx: Clinical exam:x,y
years 1–2, every 3 mo then years 3–5, every 6 mo

N0,N1: Clinical exam:x,y
years 1–2, every 6 mo then years 3–5, every 12 mo

N2,N3: • Clinical exam:x
years 1–2, every 3–6 mo then years 3–5, every 6–12 mo
Imaging: g Chest (CT
or x-ray)
◊ years 1–2, every 6 mo
Abdominal/pelvic (CTg or MRIg) ◊ year 1, every 3 mo then
◊ year 2, every 6 mo

Question 39

RECURRENT DISEASE

Recurrence of penile lesion:

Answer 39

Treat according to recurrence stage

Question 40

RECURRENT DISEASE
Local recurrence in inguinal region
No prior inguinal lymphadenectomy or RT

Answer 40

Single, mobile, <4cm LN –> percutaneous LN biopsy –> if negative, surveillance; if positive, ILND, then if pN1, surveillance; if pN2-3 –> PLND ± adjuvant chemotherapy or chemoRT

OR

Chemoradiotherapy

OR

Chemotherapy

Question 41

RECURRENT DISEASE
Local recurrence in inguinal region
Prior inguinal lymphadenectomy or RT

Answer 41

Fixed node, ≥4 cm node, or cN2/N3 disease –> Perc. LN biopsy –> treat accordingly

Chemotherapy then ILND 
OR 
ILND
OR
ChemoRT (if no prior RT)

Then surveillance

Question 42

METASTATIC DISEASE

Answer 42

Systemic chemotherapy
Cross-sectional imaging of chest/abdomen/pelvis

Complete/partial response or stable –> consolidation surgery –> surveillance

No response: subsequent line systemic therapy or consider radiotherapy for local control or clinical trial/best supportive care

Question 43

TOPICAL THERAPY

Answer 43

• For patients with Tis or Ta disease:

Imiquimod 5%, apply at night three times per week for 4–16 weeks. 5-FU cream 5%, apply twice daily for 2–6 weeks.

Question 44

LASER THERAPY

Answer 44

selected (clinical stage Tis, Ta, and T1 Grade 1–2) primary penile tumors

Application of 3%–5% acetic acid to the potentially affected genital skin can be used to identify suspected sites of human
papillomavirus (HPV)-infected skin that turns white upon exposure

smoke) evacuator is required during penile laser treatments

CO2, Nd:YAG, KTP

Question 45

Wide Local Excision

Answer 45

Early stage penile cancer
Margins depend on location:
- Shaft = wide local excision, with or without circumcision
- Distal prepuce = circumcision alone

STSG or FTSG
Positive margins = re-resection may be considered

Glans resurfacing in highly select patients

Question 46

Mohs Micrographic Surgery

Answer 46

• Mohs surgery is an alternative to wide local excision in select cases.
Thin layers of cancerous skin are excised and viewed microscopically until a tissue layer is negative for the tumor.
Allows for increased precision, though the success rate declines with higher stage disease.
• May be preferable for a small superficial lesion on the proximal shaft to avoid total penectomy for an otherwise fairly low-risk lesion.

Question 47

Penectomy

Answer 47

Standard for high-grade
Functional penile stump must be preserved, negative margins must be obtained
Partial or total penectomy when invasion into corpora cavernosa is necessary to achieve negative margins
INTRAOP FROZEN sections to determine margins

Question 48

Surgical management for inguinal and pelvic LNs

Answer 48

Standard or modified ILND or DSNB is indicated in patients with penile cancer in the absence of palpable inguinal adenopathy if high-risk
features for nodal metastasis are seen in the primary penile tumor: Lymphovascular invasion
≥pT1G3 or ≥T2, any grade
>50% poorly differentiated
• DSNB is only recommended if the treating physician has experience with this modality.
• If positive lymph nodes are found on DSNB, ILND is recommended.
• PLND should be considered at the time or following ILND in patients with ≥2 positive inguinal nodes on the ipsilateral ILND site or in the
presence of extranodal extension on final pathologic review.
• A bilateral PLND should be considered either at the time or following ILND in patients with ≥4 positive inguinal nodes (in total among both
sides).1

Question 49

NAC prior to ILND or PLND

Answer 49

TIP: paclitaxel, ifosfamide, cisplatin

NAC with TIP preferred (prior to ILND) for >= 4 cm ILN if fNA is positive for metastatic penile CA

**Patients not eligible to receive TIP and are surgical candidates should undergo surgery without neoadjuvant chemotherapy.

Question 50

Adjuvant chemotherapy after ILND or PLND

Answer 50

Preferred regimen: TIP
Other: 5-FU + cisplatin

Consider adjuvant EBRT or chemoRT for patients with high-risk features: 
PLN metastates
Extranodal extension
Bilateral inguinal LNs involved
4-cm tumor in LNs

Question 51

Subsequent-line Systemic Therapy for Metastatic Disease

Answer 51

Preferred:

• Clinical trial
• Pembrolizumab if unresectable or metastatic microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR)

Useful in Certain Circumstances

• Paclitaxel
• Cetuximab

Question 52

Radiosensitizing Agents and Combinations (ChemoRT)

Answer 52

Preferred:

• Cisplatin alone or combination with 5-FU
• Mitomycin C in combination with 5-FU

Oher:
- Capecitabine

Question 53

TIP regimen

preferred

Answer 53

Paclitaxel 175 mg/m2 IV over 3 hours on Day 1 Ifosfamide 1200 mg/m2 IV over 2 hours on Days 1–3 Cisplatin 25 mg/m2 IV over 2 hours on Days 1–3 Repeat every 3 to 4 weeks

Question 54

5-FU + cisplatin regimen (not recommended for neoadjuvant setting)

Answer 54

Continuous infusion 5-FU 800–1000 mg/m2/day IV on Days 1–4 or Days 2–5
Cisplatin 70–80 mg/m2 IV on Day 1
Repeat every 3 to 4 weeks