PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
Urethral cancers vary in their clinical expression as a function of anatomic location in both the male and female urethra.
PERSPECTIVE AND PATTERNS OF SPREAD
Cancers of the urethra are quite uncommon. They occur more often among females. Common presentation is a structure interfering with urination in males; in females, urinary frequency, hesitancy, and a palpable urethral mass are often noted. Bleeding without a history of trauma or venereal disease should raise suspicion of an underlying malignancy. On examination, a palpable urethral mass especially in females is present in the majority of cases (75%) and can appear as papillary growths, soft, fungating lesions, or ulcerations with a foul-smelling discharge. Obstructive symptoms and incomplete voiding (66%) also lead patients to seek medical evaluation, as well as relief of symptoms.
The patterns of cancer spread relate to surrounding anatomy in males and females. In the male, it advances and eventually may invade the penis, prostate, or urinary bladder whereas, in the female, vaginal invasion along the anterior wall of the vagina is more frequent. The labia can be involved if it spreads inferiorly or into the bladder if it progresses superiorly (Fig. 40.2; Table 40.2).
Cancer of the urethra is the only genitourinary cancer that is more common in women than men. Predisposing factors are repeated infections; human papilloma virus (HPV) may be a factor. Urethrorrhagia is often the early symptom, then stricture or mass in anterior vaginal wall.
Cancer of the urethra in males, in contrast, usually is initiated as noted with a stricture and occurs in 25% to 75% of cases, most often in the bulbomembranous urethra, associated with HPV.
PATHOLOGY
The histopathology differs in incidence in males versus females: squamous cell carcinoma (80% vs. 60%), transitional cell (15% vs. 20%), and adenocarcinoma (5% vs. 10%) (Table 40.1; Figure 40.1).
Figure 40.1 | Urothelial carcinoma in situ. The urothelial mucosa shows nuclear pleomorphism and lack of polarity from the basal layer to the surface, without evidence of maturation.
Figure 40.2 | A. Coronal. B. Transverse. Patterns of spread (cancer crab) of urethral cancer are color coded for stage: Tis or Ta, yellow; T1, green; T2, blue; T3, purple; and T4, red. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern (SIMLAP, Table 40.2).
TNM STAGING CRITERIA
TNM STAGING CRITERIA
Urethral cancers behave in an inverse fashion to penile cancers. Tis cancer is limited to the mucosa, and T1, to the subepithelial connective tissues. T2 is invasion of the corpus spongiosum; T3, to the corpus cavernosum; and T4, to adjacent organs (Fig. 40.3). Urethral cancers are more common in females and require histopathologic evidence of their spread to be accurately staged.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
For urothelial (transitional cell) carcinoma of the prostate, T1 category is defined as tumors invading subepithelial connective tissue.
The seventh edition of the AJCC Cancer Staging Manual diagrams the progression from Ta to Tis to T1 and T2 i.e., confined to epithelial mucosa, subepithelial connective tissue, then urethral muscle. In contrast, prostatic urethral cancer progression is the same for Tis and T1 but T2 is invasion of prostate stroma (Fig. 40.3).
The TNM staging matrix is color coded for identification of stage group once the T and N stages are determined (Table 40.3).
Renal pelvis, urinary bladder, and urethral cancers have four stages, but with the addition of stages 0a 0is for Ta noninvasive cancer and Tis cancer in situ, respectively, the number of stage groups increases to six. T stage determines stage group.
URETHRA
Figure 40.3 | TNM urethra cancer diagram. Urethra cancers, when extensive in males, T3, may require amputation. Vertically arranged with T definitions on the left and stage groupings on the right. Color bars are coded for stage: Stage 0is and 0a, 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 base of the urethra inferior to the boney pelvis (Fig. 40.4).
The urethral cancers in the male urethra originate at the bladder neck to the external urethral meatus (Fig. 40.4C).
In the female, the urethra courses from the bladder neck to an opening in the vestibule of the vagina. It is intimately related to the anterior wall of the vagina (Fig. 40.4D).
T-oncoanatomy
The T-oncoanatomy is displayed in three planar views in Fig. 40.5:
• Coronal: The posterior urethra is subdivided into the membranous urethra, the portion passing through the urogenital diaphragm (external urethral sphincter), and the prostatic urethra. The prostatic urethra is covered by transitional cell epithelium and gives rise to transitional cell carcinomas (Fig. 40.5A).
• Sagittal: The distal spongy portion of the urethra is covered by stratified squamous epithelium, changing to pseudostratified columnar epithelium proximally in the membranous portion. The common cancer is squamous cell cancer (Fig. 40.5B).
• Transverse: The spongy portion of the urethra lies in the corpus spongiosum of the penis (Fig. 40.5C).
Figure 40.4 | A, B. Orientation of T-oncoanatomy. The anatomic isocenter for three-planar anatomy of urethra is below the pelvis. A. Coronal. B. Sagittal. C. Male urethra. D. Female urethra.
Figure 40.5 | 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. 40.3) and patterns of spread (Fig. 40.2) and SIMLAP table (Table 40.2). Connecting the dots in similar colors will provide an appreciation for the three-dimensional oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
In the male, 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 membranous 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 (Table 40.4; Fig. 40.6A, top).
In the female, lymphatics of the anterior urethra drain into the superficial and then deep inguinal nodes. The posterior urethra drains into obturator and internal iliac nodes, similar to the bladder. External iliac nodes are a sign of advancement, and sentinel lymph nodes tend to be inguinal or femoral nodes.
In females, inguinal nodes are present in 30% of patients, and, if palpable, they are likely to be positive (Fig. 40.6B).
In males, the inguinal nodes are palpable in 20%, in contrast to the case for the penis, whereas 50% have palpable nodes and require pathologic assessment to be certain of cancer.
M-ONCOANATOMY
In the male, 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 and into iliac vein and inferior vena cava (Fig. 40.6C).
In the female, depending on location, hematogenous spread leads to drainage into vesical and internal iliac veins, the inferior vena cava, and the right side of the heart into the lungs. Proximal or entire urethral cancers are more aggressive and tend to metastasize (see Fig. 40.6D).
Figure 40.6 | A. N-Oncoanatomy. B. M-oncoanatomy.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Imaging is reserved for determining metastatic pelvic nodal involvement and remote metastases when stage is advanced. The primary site is assessed by physical examination—inspection and palpation followed by cystourethroscopy with biopsy and cytology. Contrast filling of bladder and voiding cystometrogram are worthwhile (Table 40.5, Fig. 40.7).
Pathologic Staging
Complete resection of the primary and part of the penis requires determination of appropriate clearance of surgical margins. Lymphadenectomy specimens should note number, size, and extranodal extensions. Assignment of stage following resection allows depth of invasion to be determined. In males, urethral neoplasms can arise in prostate epithelium or ducts and are classified as prostate urethral cancer.
Oncoimaging Annotations
• Diagnosis of urethral cancer is by cystoscopy and biopsy.
• Magnetic resonance imaging is superior to computed tomography in the evaluation of local tumor extent.
Figure 40.7 | MRI of normal membranous urethra in the transverse plane. 1. corpus spongiosum (bulb of the penis) 2. septum of the corpus spongiosum 3. bulbous urethra 4. crus of the corpus cavernosum 5. corpus cavernosum 6. deep cavernous a. 7. septum of the corpus cavernosum 8. Buck's fascia and tunica albuginea 9. spermatic cord 10. anal canal 11. sphincter ani externus m. 12. ischiocavernosus m. 13. transversus perinei superficialis m. 14. bulbospongiosus m. 15. ischium
PROGNOSIS AND CANCER SURVIVAL
PROGNOSIS
The limited number of prognostic factors are listed in Table 40.6.
CANCER STATISTICS AND SURVIVAL
When considered together, the male genital and urinary systems are the major sites of malignancy. Prostate cancer alone accounts for 200,000 new patients annually. There are 100,000 new urinary tract cancers and 2.5-fold more male genital cancers, or 250,000 cases annually.
The dramatic gains in survival are due to multidisciplinary achievements in screening, early detection, precise diagnoses, and effective multimodal therapies. The cancer statistics reveal perhaps the greatest gains in survival in oncology over the last five decades. In local stage I, male genitourinary tumors are 90% to 100% curable according to the latest Surveillance Epidemiology and End Results data: kidney, 90%; bladder, 94%; testes, 99%; and prostate, 100%. Mortality rates are declining. The pediatric Wilms’ tumor was the first malignancy in childhood to be cured, achieving >90% long-term survival, heralding the success of multimodal treatment that would be achieved in adult tumors in urology (Fig. 40.8).
Figure 40.8 | Observed and overall survival rates for 1,278 patients with urethral cancer classified by the current American Joint Committee on Cancer staging classification. Data taken from the National Cancer Data Base (Commission on Cancer of the American College of Surgeons and the American Cancer Society) for the years 1998 to 2002. Stage 0a includes 129 patients; stage 0is, 170; stage I, 243; stage II, 193; stage III, 250; and stage IV, 293. (Data from Edge SB, Byrd DR, and Compton CC, et al., AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 509.)