Campbell Penile CA Review + NCCN Penile 2021 Flashcards
Penile lesion NOT associated with viral infection
BXO
Associated with viruses: HPV infection: Condyloma Bowenoid Erythroplasia of Queyrat
HHV-8:
Kaposi sarcoma
Infection associated with cervical dysplasia: ___
HPV infection: principal etiologic agent in cervical cancer
Major difference between Bowen disease vs. Erythroplasia of Queyrat
Location!
Queyrat: Glans penis or prepuce
Bowen disease: penile shaft skin, perineal, genitalia
Kaposi sarcoma etiologic agent
Human Herpesvirus 8
Where do penile cancers most commonly arise?
Glans
Glans (48%)
Prepuce (21%)
Risk factors for development of SCCA of the penis: ___
Smoking
HPV infection
Phimosis
Tobacco chewing
Campbell: Gonorrhea NOT a risk factor
NCCN: STD = risk factor
Preventive strategies to decrease incidence of penile cancer: ___
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.
Campbell review TRUE statements:
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
Penile cancer initial spread: ___
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)
Hypercalcemia in penile cancer
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.
Imaging with 100% sensitivity for cavernosal invasion: ___
Ultrasonography
Stage T2 tumors: ___
Invade the corpus spongiosum but not the cavernosum
Strongest prognostic factor for survival of penile cancer: ___
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.
Criteria for curative resection (> 70% 5-yr survival) in patients treated for LN mets: ___
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
Surgical staging is strongly considered in: ___
palpable adenopathy.
stage T1b or greater primary tumor.
presence of vascular invasion in primary tumor.
presence of predominantly high-grade cancer in primary
tumor.
Inguinal procedures for non-palpable adenopathy: ___
(1) dynamic sentinel node biopsy,
(2) superficial dissection,
(3) modified complete dissections, and
(4) laparoscopic and robotic approaches.
Adjuvant or neoadjuvant chemotherapy for the following: ___
single pelvic nodal metastasis
extranodal extension of cancer
fixed inguinal masses
single 6-cm inguinal lymph node
Histology of majority of penile cancers: ___
SCCA
** The majority of tumors of the penis are squamous cell carcinomas demonstrating keratinization, epithelial pearl formation, and various degrees of mitotic activity.
Chemotherapeutic agent with significant pulmonary toxicity
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.
Primary penile melanoma is rare because: ___
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.
Lymphomatous infiltration of the penis is most likely due to: ___
Diffuse disease
** When lymphomatous infiltration of the penis is diagnosed, a thorough search for systemic disease is necessary.
Most frequent sign of metastatic involvement of the penis: ___
Priapism
** The most frequent sign of penile metastasis is priapism; penile swelling, nodularity, and ulceration have also been reported.
Bushcke-Lowenstein tumor vs. condyloma acuminatum
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.
Treatment for small lesions of erythroplasia of Queyrat
Topical 5% 5-FU
Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
Local excision
Imiquimod
Standard treatment of choice for condyloma
Imiquimod cream
3 types of penile Tis
Bowenoid papulosis
Bowen disease
Erythroplasia of Queyrat
Initial evaluation of suspicious penile lesion:
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
PRIMARY TREATMENT
Tis or Ta
Topical therapyb or b Wide local excision or b Laser therapy (category 2B) or Complete glansectomy or Mohs surgery in select cases (category 2B)
PRIMARY TREATMENT
T1
Grade 1-2
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
PRIMARY TREATMENT
T1
Grade 3-4
Wide local excisionb or c,d Partial penectomy or c,d Total penectomy or Radiotherapy or Chemoradiotherapy
PRIMARY TREATMENT
T2 or greater
Partial penectomyc,d
or c,d Total penectomy or RT or chemoRT
NON-PALPABLE INGUINAL LNs
LOW RISK:
Surveillance
INTERMEDIATE/HIGH RISK T1b Any T2 or greater -- chest CT and abdominal/pelvic CT -- ILND or DSNB
PALPABLE INGUINAL LNs, NON-BULKY
after Chest CT + abdominal/pelvic CT
Unilateral LN <4 cm mobile
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
PALPABLE INGUINAL LNs,
BULKY
Unilateral lymph nodes
≥4 cm (mobile) –> percutaneous LN biopsy
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
PALPABLE INGUINAL LNs BULKY
Unilateral lymph nodes (fixed)n or bilateral lymph nodes (fixed or mobile) –> percutaneous LN biopsy
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
ENLARGED PELVIC LNs
Percutaneous biopsy if technically feasible
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
SURVEILLANCE SCHEDULE
Anatomic Site
Primary lesion
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
LNs
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
RECURRENT DISEASE
Recurrence of penile lesion:
Treat according to recurrence stage
RECURRENT DISEASE
Local recurrence in inguinal region
No prior inguinal lymphadenectomy or RT
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
RECURRENT DISEASE
Local recurrence in inguinal region
Prior inguinal lymphadenectomy or RT
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
METASTATIC DISEASE
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
TOPICAL THERAPY
• 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.
LASER THERAPY
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
Wide Local Excision
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
Mohs Micrographic Surgery
• 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.
Penectomy
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
Surgical management for inguinal and pelvic LNs
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
NAC prior to ILND or PLND
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.
Adjuvant chemotherapy after ILND or PLND
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
Subsequent-line Systemic Therapy for Metastatic Disease
Preferred:
- Clinical trial
- Pembrolizumab if unresectable or metastatic microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR)
Useful in Certain Circumstances
- Paclitaxel
- Cetuximab
Radiosensitizing Agents and Combinations (ChemoRT)
Preferred:
- Cisplatin alone or combination with 5-FU
- Mitomycin C in combination with 5-FU
Oher:
- Capecitabine
TIP regimen
preferred
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
5-FU + cisplatin regimen (not recommended for neoadjuvant setting)
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
