Radiation Oncology: A Question-Based Review

Penile Cancer

Jing Zeng and Alexander Lin

image Background

What is the estimated annual incidence of penile cancer Dx in the U.S.? What % of male cancers does this represent? How is this different in developing countries?

There are ~1,500 new cases/yr of penile cancer in the U.S., representing <1% of male cancers. In developing countries, it can account for 10%–20% of all male cancers.

Name 3 factors associated with the risk of developing penile cancer.

Risk factors for penile cancer:

1.     Lack of circumcision

2.     Phimosis

3.     HPV infection

4.     HIV infection

Others factors that may also be associated include smoking, PUVA therapy, and family Hx.

What causes condyloma acuminata?

Condyloma acuminata, more commonly known as genital warts, are associated with HPV infection. They are usually benign but can undergo malignant transformation.

What is the difference between erythroplasia of Queyrat (EQ) and Bowen Dz?

Both EQ and Bowen Dz are CIS conditions. EQ occurs within the penile mucocutaneous epithelium (glans and prepuce), whereas Bowen Dz occurs within follicle-bearing epithelium (penile shaft).

What are the 2 most common anatomic locations for penile cancer?

The glans and prepuce are the 2 most common locations for penile cancer. Less common locations include the coronal sulcus and the shaft. Lesions can appear as a mass, ulceration, or inflammation.

To what LNs do penile cancers primarily drain to 1st?

Inguinal LNs are the initial site of nodal involvement in penile cancers → iliac and pelvic nodes.

What is the anatomic position of the penis?

The anatomic position of the penis is erect; the descriptors dorsal and ventral refer to the anatomic position.

Approximately what % of men with penile cancer and palpable inguinal LAD have pathologically positive nodal mets?

Overall, ~58% of palpable inguinal nodes in pts with penile cancer are actually positive for cancer mets on pathology. The rest of the nodes are reactive.

In men with penile cancer and clinically negative nodes, what is the likelihood of occult nodal mets?

In men with penile cancer and clinically negative nodes, the likelihood of occult nodal mets depends on the tumor stage, grade, and presence of LVI. Roughly, it can be 11%–20% for T1 lesions and up to 60%–75% for T2-T3 lesions.

What % of men with penile cancer present with DM lesions?

Hematogenous spread of penile cancer is rare until late in the Dz course and is found in only 1%–10% of men at initial presentation.

What are the most common sites for DM in penile cancer?

Lung, liver, and bone are the most common sites for DM in penile cancer.

What is the most common histology in penile cancer?

Squamous cell carcinoma accounts for 95% of penile malignancies. Other histologic subtypes such as sarcoma, urethral tumors, lymphoma, and basal cell carcinoma are extremely rare.

image Workup/Staging

What is the workup for penile cancer?

Penile cancer workup: H&P, CBC, chemistry panel, MRI penis/pelvis. Consider PET/CT and inguinal sentinal LN Bx.

How should clinically negative LNs in penile cancer be evaluated?

Clinically negative LNs in penile cancer should be evaluated with CT, MRI, or PET scan, but the FPR and FNR are both high regardless of the imaging modality. Inguinal sentinel LN Bx is promising (FNR 7%).

Should clinically negative nodes in penile cancer undergo inguinal dissection?

The toxicity of inguinal LND should be weighed against the likelihood of occult nodal mets in penile cancer. LND may be considered for ≥T2 tumors or for high-grade lesions. Recent studies suggest that sentinel LN Bx may be a reasonable alternative (Leijte JA et al., JCO 2009).

How should clinically positive LNs in penile cancer be evaluated?

Historically, palpable inguinal LNs in penile cancer can be managed by a 6-wk trial of antibiotics. Newer, alternative approaches include FNA or open Bx.

What is the AJCC 7th edition (2009) T staging for penile cancer?

1.     Tis: CIS only

2.     Ta: noninvasive verrucous carcinoma

3.     T1a: invades subepithelial connective tissue without LVI and is not poorly differentiated (i.e., not grades 3–4)

4.     T1b: invades subepithelial connective tissue with LVI or is poorly differentiated

5.     T2: invades corpora spongiosum or cavernosum

6.     T3: invades urethra

7.     T4: invades other adjacent structures

What is the AJCC 7th edition (2009) clinical and pathologic N staging for penile cancer?

1.     cN1: palpable mobile unilat inguinal LN

2.     cN2: palpable mobile multiple or bilat inguinal LN

3.     cN3: palpable fixed inguinal nodal mass or pelvic LAD

4.     pN1: single inguinal LN

5.     pN2: multiple or bilat inguinal LN

6.     pN3: LN ECE or pelvic LN

What is the AJCC 7th edition (2009) stage grouping for penile cancer?

1.     Stage I: T1a, N0, M0

2.     Stage II: T1b-T3, N0, M0

3.     Stage IIIa: T1-3, N1, M0

4.     Stage IIIb: T1-3, N2, M0

5.     Stage IV: T4 or N3 or M1

image Treatment/Prognosis

How are noninvasive penile cancers treated?

CIS of the penis can be treated with topical 5-FU with good LC and excellent cosmetic outcome. Other methods that are acceptable include laser surgery, cryotherapy, photodynamic therapy, and local excision. Fulguration alone has a high recurrence rate and is not an acceptable option.

What are the Tx options for pts with early-stage penile cancer (T1-T2, <4 cm)?

Early-stage penile cancer Tx options include penectomy (partial or total) or an organ preservation approach using EBRT, brachytherapy, or CRT (cisplatin based).

How are locally advanced (T3-T4) penile cancers managed?

For locally advanced penile cancers, consider CRT, with surgery reserved for salvage or total penectomy. Induction chemo → penile-preserving Tx is under investigation.

What surgical margin is typically required for total or partial penectomy for Tx of invasive penile cancer?

For penile cancer resection, a 2-cm proximal margin is needed to ensure a 10–15-mm histologic margin, which appears to give good LC.

What length of corpus cavernosum is required in order for 50% of men to be able to have sexual intercourse?

~45% of men are able to have adequate sexual intercourse with about 4–6 cm of corpus cavernosum.

What residual penile length is required for men to be able to urinate in the standing position?

~2.5–3 cm of residual penile length is required for men to be able to urinate in the standing position.

Name 3 penile-sparing techniques for treating penile cancer.

Mohs surgery, laser therapy (mostly for smaller T1-T2 tumors), and RT are all penile-sparing techniques for treating penile cancer.

What surgical procedure should accompany any RT for penile cancer?

Circumcision should accompany any RT for penile cancer in applicable pts. This allows for better inspection and staging of the lesion as well as helps to alleviate some of the side effects of RT.

In megavoltage EBRT for penile cancer, should bolus be used?

Yes. Bolus should be used in megavoltage EBRT for penile cancer for dose buildup at the surface (usually a wax or plastic cast with the penis suspended above the abdomen or secured against the abdomen if also treating nodes).

In EBRT for penile cancer, what is the CTV and what dose is typically prescribed?

In EBRT for penile cancer, the CTV is the entire penile length and typically goes to 45–50 Gy, with a 10–20 Gy boost to the tumor + a 2-cm margin. Pelvic fields + inguinal nodes are treated to 45 Gy if the pelvic nodes are included in the Tx. Boost to any clinically gross Dz (65–70 Gy).

What types of penile cancer lesions are acceptable for brachytherapy?

Penile cancer lesions that can be treated with brachytherapy are typically <4 cm in diameter and have <1 cm of corpora invasion (T1-T2).

What are 2 ways of delivering brachytherapy in penile cancer, and what is the dose prescribed?

Brachytherapy for penile cancer can be delivered by either (a) using molds containing sources such as iridium-192 (less appropriate for pts with short penile length) or (b) using interstitial implants by placing catheters 1–1.5 cm apart, perpendicular to the penile axis and afterloading with sources. The target dose is 55–60 Gy, with the urethral dose limited to 50 Gy.

How are pts with penile cancers simulated for EBRT?

Simulation for EBRT for penile cancer Tx: supine position and frog-legged, Foley catheter, and penis surrounded with bolus material. If treating pelvic and inguinal nodes, the penis is secured cranially into the pelvic field.

What data supports the use of concurrent CRT in treating penile cancer?

There is no data directly supporting the use of concurrent CRT in treating penile cancer, but extrapolation from cervical cancer and anal cancer data has led to the increasing use of concurrent cisplatin-based CRT.

Name 4 chemo drugs active against penile cancer.

Agents active against penile Ca:

1.     5-FU

2.     Cisplatin

3.     Bleomycin

4.     Methotrexate

5.     Irinotecan

Although metastatic penile cancer is chemosensitive, responses are brief and incomplete, and eventual progression is inevitable.

What is the most important prognostic factor in predicting survival in penile cancer pts without DMs?

Inguinal LN mets is the most important prognostic factor in predicting survival in penile cancer pts without DMs.

What is the overall cure rate for surgically treated penile cancer pts +/− node-negative Dz?

The 5-yr survival for penile cancer pts without nodal Dz is 80%–100%, while the 5-yr survival for pts with nodal mets is 32%–50%.

What are the expected LC rates for pts managed with EBRT or brachytherapy for penile cancers?

LC estimates vary widely, likely depending on pt selection. In a well-selected pt with T1-T3 penile cancer treated with EBRT or brachytherapy, LC (i.e., penile preservation rate) is 80%–90% (5–10 yrs follow-up). (Crook JM et al., IJROBP 2005)

How does surgery compare to RT as the initial modality in the management of penile cancers?

Retrospective comparisons between surgery and RT suggest that surgery is associated with superior initial LC as a primary modality, though these studies suffer from significant selection bias. Overall LC does not appear to differ when allowing for surgical salvage. The benefit of RT is penile preservation. Long-term OS appears similar between the 2 modalities.

Estimate the MS in men with localized, regional (node+), or metastatic penile carcinoma.

MS in men with penile carcinoma:

1.     Localized: 4 yrs

2.     Regional: 2.5 yrs

3.     Metastatic: 7 mos

(Rippentrop M et al., Cancer 2004)

image Toxicity

How should pts with penile cancer who rcv definitive therapy be followed?

Penile cancer pts treated with penectomy with nodal dissection can be followed q4mos for 2 yrs, then q6mos for an additional 3 yrs. Pts treated with penile-sparing therapy or those who did not undergo LND should be followed q2mos for yrs 1–2, then q6mos for an additional 3 yrs.

Name 3 acute side effects that may occur during RT for penile cancer.

Urethral mucositis, edema, and secondary infection are experienced by nearly all pts during RT for penile cancer.

Name 5 long-term complications from RT for penile cancer.

Telangiectasia, superficial necrosis, urethral stricture, fistula formation, meatal stenosis, and dyschromia are all common long-term toxicities from RT for penile cancer.

What doses increase the risk of urethral strictures from fibrosis or stenosis?

Doses >60 Gy increase the risk of urethral stenosis and fibrosis.

What are the side effects from inguinal LND in pts with clinically negative nodes in penile cancer?

Side effects from inguinal LND include lower extremity edema, wound complications, and DVT.

What are the doses that cause sterilization?

2–3 Gy is sufficient for sterilization.