PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
Cross-sectional anatomy of the penis reflects the staging system of penile and urethral cancers.
PERSPECTIVE AND PATTERNS OF SPREAD
Penile and urethral cancers are uncommon in the United States, accounting for 1% of all malignancies in men. Circumcision has been shown to be effective in decreasing and preventing such cancers in Jewish, Nigerian, and Ugandan men who practice circumcision. Phimosis and smegma correlate with penile cancers. A relationship to sexually transmitted diseases, chronic infection, and trauma has been implicated in urethral cancers. The age group most afflicted are men in their 50s and 60s. Presenting symptoms are superficial nodular lesions, ulcerative sores, pain and itching, bleeding, and urinary burning. Palpable inguinal nodes are often present but may be ignored. If ignored, adenopathy may be present in 30% to 45% of cases; fortunately, at least half are due to associated infection rather than cancer.
The skin continues distal to the glans penis to form a smooth, retractable sheath, the prepuce, which is lined by mucous membrane and has a moist, stratified squamous epithelium. The prepuce is most often the site of premalignant in situ lesions, followed by the glans. Bowen disease is squamous cell cancer in situ that may involve the skin of the shaft. It often appears as a dull-red plaque with crusting and oozing. Erythroplasia of Queyrat is an epidermoid cancer in situ that involves the mucosal or mucocutaneous junction at the prepuce or glans.
The patterns of spread vary with location. Cancers of the skin and mucous membrane of the glans invade superficially and then penetrate into the corpus spongiosum and cavernosum (Fig. 39.2; Table 39.2).
There are a variety of presentations, as an ulcer, to a friable mass, or an exophytic papillary tumor. Once erosion into the urethra occurs, multiple fistulas lead to a “watering can” perineum. A curious differential diagnosis is that of mass lesion due to condyloma acuminatum, which is benign.
PATHOLOGY
The predominant cancer is squamous cell carcinoma, as expected with mucous membranes. Basal cell cancers account for only 1% to 2% of penile cancers. The glans (60%) and the prepuce (30%) are most often the sites of origin of cancer. Skin of the shaft accounts for 10% (Table 39.1; Fig. 39.1).
Condyloma acuminata of the penis is an important differential diagnosis, showing benign epidermal hyperkeratosis, parakerotosis, acanthosis, and papillomatosis.
Figure 39.1 | Condyloma acuminata of penis is an important differential diagnosis showing benign epidermal hyperkeratosis, parakerotosis, acenthosis, and pappilomatosis.
Figure 39.2 | A. Coronal. B. Transverse. Patterns of spread (cancer crab) of penis cancer are color coded for stage: Tis or Ta, yellow; T1, green; T2, blue; T3, purple; and T4, red. The patterns of spread of penis assumes erect position as in diagram. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern (SIMLAP, Table 39.2).
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The staging of penile cancers and urethral cancers has been based on depth of invasion rather than size. In the early versions of the International Union Against Cancer classification, it was classified similarly to other skin cancers. There have been no changes in penile cancer staging since the third edition; urethral cancers are noted separately. Cross-sectional anatomy of the penis reflects the staging system of penile and urethral cancers.
Initial superficial stage Tis is cancer in situ, and Ta is verrucal, noninvasive lesion. Subepithelial or subcutaneous spread is T1. Once invasion occurs through the deep (Buck's) fascia, the corpus spongiosum or cavernosum is invaded (stage T2). Invasion into urethra is T3 and into adjacent structures is T4 (Fig. 39.3).
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The following changes in the definition of TNM and the Stage Grouping for this chapter have been made since the Sixth Edition (Fig. 39.3).
• T1 has been subdivided into T1a and T1b based on the presence or absence of lymphovascular invasion or poorly differentiated cancers.
• T3 category is limited to urethral invasion, and prostatic invasion is now considered T4.
• Nodal staging is divided into both clinical and pathologic categories.
• The distinction between superficial and deep inguinal lymph nodes has been eliminated.
• Stage II grouping includes T1b N0M0 as well as T2-3 N0M0.
With the Seventh Edition, lymph node staging is divided into a clinical vs. pathologic stage definition, reflecting the importance and impact of node positive spread. Location and mobility of inguinal nodes is the key clinical criteria, whereas spread to deep pelvic external iliac nodes is a most important determinant of survival.
Lymphatic and vascular embolizations are independent predictive variables of inguinal lymph node involvement in patients with squamous cell carcinoma of the penis (Table 39.3A).
The TNM staging matrix is color coded for identification of stage group once T and N stages are determined (Table 39.3B). T stage determines stage group, and N1 can occur with early cancers T1, T2, as well as with advanced T3 lesions.
PENIS
Figure 39.3 | TNM penis cancer diagram. Vertically arranged with T definitions on the left and stage groupings on the right. Color bars are coded for stage: stage 0, yellow; I, green; II, blue; III, purple; IV, red; and metastatic, black.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The isocenter is taken at the penile base inferior to the bony pelvis (Fig. 39.4).
T-oncoanatomy
The T-oncoanatomy is displayed in three planar views in Fig. 39.5:
• Coronal: The penis and urethra have an anterior projectile portion and a posterior anchoring part into the prostate in males.
• Sagittal: These are surrounded by a deep penile fascia (Buck's fascia), which is separated from skin by a layer of connective tissue. Penile and urethral cancers mirror image their patterns of invasion and advancement as to depth of tissue penetration.
• Transverse: The axial cross section identifies the major anatomic features: The urethra is embedded in the corpus spongiosum and the main erectile corpora cavernosum.
Figure 39.4 | Orientation of T-oncoanatomy. The anatomic isocenter for the three-planar anatomy of the urethra is below the pelvis. A. Coronal. B. Sagittal.
Figure 39.5 | T-oncoanatomy. Connecting the dots. Structures are color coded for cancer stage progression. The color code for the anatomic sites correlates with the color code for the stage group (Fig. 39.3) and patterns of spread (Fig. 39.2) and SIMLAP table (Table 39.2). Connecting the dots in similar colors will provide an appreciation for the three-dimensional oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The lymphatic channels of the prepuce and penis are rich, and the shaft skin drains into inguinal nodes. The rich anastomoses at the base of the penis result in bilateral drainage into superficial and deep inguinal nodes. Sentinel nodes are often located at the junction of saphenous and superficial epigastric veins. The lymphatics of the bulbomembranous and prostatic urethra follow three routes: external iliac nodes, obturator and internal iliac nodes, and presacral nodes. Pelvic external iliac nodes are seldom involved without inguinal node involvement first (Fig. 39.6A,B; Table 39.4).
An important observation is the extensions of due extranodal invasion. Mobility of nodes versus matting, fixation and ulceration of inguinal nodes. Once there is evidence of nodal invasion, the 5-year survival drops to 5% to 15%, an ominous outcome.
A very interesting set of nomograms were published by Ficarra et al.* relating a variety of primary characteristics that predict for lymph node involvement:
• Tumor thickness
• Growth pattern
• Grade
• Embolization
• Corpus cavernosum
• Corpus spongiosum
• Urethral infiltration
REGIONAL LYMPH NODES
• The regional lymph nodes are as follows:
• Superficial and deep inguinal (femoral)
*Ficarra V, Zattoni F, Artibani W, et al. J Urol 2006;175(5): 1700–1704; discussion 1704–1705.
• External iliac
• Internal iliac
• Pelvic nodes, NOS
Clinical examination by palpation of the inguinal region is required. Computed tomography is a useful adjunct to palpation in patients with palpable inguinal adenopathy or those in whom palpation is unreliable (i.e., obese, prior inguinal surgery).
M-ONCOANATOMY
Distant metastases are uncommon, except in advanced disease at the base of the penis, despite the rich vascular anastomoses and penile blood supply, which drains into the dorsal vein of the penis and then into the periprostatic and perivesical venous plexus (Fig. 39.6C).
Figure 39.6 | A. Nomogram to predict lymph node involvement for squamous cell carcinoma of the penis. (From Ficarra V, Zattoni F, Artibani W, et al. Nomogram predictive of pathological inguinal lymphnode involvement in patients with squamous cell carcinoma of the penis. J Urol 2006;175:1700.)
Figure 39.6 | B. N-oncoanatomy. Obturator nodes of hypogastric or internal iliac chain.
Figure 39.6 | C. M-oncoanatomy.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Careful physical examination and endoscopy are adequate to determine primary extension and nodal involvement. Imaging is reserved for determining metastatic pelvic nodal involvement and remote metastases when stage is advanced. Computed tomography is preferred to magnetic resonance imaging because it is more cost-effective (Table 39.5; Fig. 39.7).
Pathologic Staging
Complete resection of the primary and of part of the penis requires determination of the appropriate clearance of surgical margins. Lymphadenectomy specimens should note number, size, and extranodal extensions.
Figure 39.7 | Axial computed tomography (CT) of level of corpora cavernosa of penis. Oncoimaging with CT is commonly applied to staging cancers, often combined with positron emission tomography to determine the true extent of primary cancer and involved lymph nodes. 1. Rectum. 2. Inferior pubic ramus. 3. Ischiorectal fossa. 4. Iliopsoas muscle. 5. Rectus femoris muscle. 6. Sartorius muscle. 7. Tensor fasciae latae muscle. 8. Vastus lateralis muscle. 9. Spermatic cord. 10. Corpora cavernosa of penis.
PROGNOSIS AND CANCER SURVIVAL
PROGNOSIS
The limited number of prognostic factors are listed in Table 39.6.
CANCER STATISTICS AND SURVIVAL
Again, Ficarra et al. have developed nomograms for both clinical and pathologic staging of lymph nodes, predicting cancer-specific survival based on mainly the inguinal lymph node status in addition to primary tumor characteristics (Fig. 39.8). Note the impact of cNo versus cN+ with the drop in survival. If this were updated using current American Joint Committee on Cancer path N+ criteria, the horizontal line would extend to between 5% and 15% as mentioned earlier.
Figure 39.8 | Nomogram predicting cancer-specific survival based on primary penile tumor characteristics and pathologic stage of inguinal lymph nodes. (From Ficarra V, Zattoni F, Artibani W, et al. Nomogram predictive of pathological inguinal lymphnode involvement in patients with squamous cell carcinoma of the penis. J Urol 2006;175:1700.)