Primary Urethral Carcinoma

5. DIAGNOSTIC EVALUATION AND STAGING

5.1. History

When becoming clinically apparent, most patients (45–57%) with primary urethral carcinoma present with symptoms associated with locally-advanced disease (T3/T4) [35]. At initial presentation visible haematuria or bloody urethral discharge is reported in up to 62% of the cases. Further symptoms of locally-advanced disease include; an extra-urethral mass (52%), bladder outlet obstruction (48%), pelvic pain (33%), urethrocutaneous fistula (10%), abscess formation (5%) or dyspareunia [35].

5.2. Clinical examination

In men, physical examination should comprise palpation of the external genitalia for suspicious indurations or masses and digital rectal examination [36]. In women, further pelvic examination and palpation of the urethra should be performed. In addition, bimanual examination, when necessary under general anaesthesia, should be performed for local clinical staging and to assess whether colorectal or gynaecological malignancies are present.

Bilateral inguinal palpation should be done to assess the presence of enlarged LNs, describing location, size, and mobility [37].

5.3. Urinary cytology

Urinary cytology is part of the standard work-up of a patient with suspected primary urethral carcinoma. Reporting of urinary cytology findings should follow the Paris system [38]. However, the role of urinary cytology in primary urethral carcinoma is limited since its sensitivity ranges between 55% and 59% [39]. Detection rates depend on the underlying histological entity. In male patients, the sensitivity for UC and SCC was reported to be 80% and 50%, respectively, whereas in female patients, sensitivity was found to be 77% for SCC and 50% for UC [39].

5.4. Diagnostic urethrocystoscopy and biopsy

Diagnostic urethrocystoscopy and biopsy enables primary assessment of a urethral tumour in terms of tumour extent, location, and underlying histology [36]. Cystoscopic examination is necessary to exclude the presence of concomitant bladder tumours [40].

A cold-cup biopsy enables accurate tissue retrieval for histological analysis and avoids artificial tissue damage. In patients with larger lesions, transurethral resection (optionally in men under penile blood arrest using a tourniquet) can be performed for histological diagnosis [41]. In patients with suspected UC of the prostatic urethra or ducts, resectoscope loop biopsy of the prostatic urethra (between the five and seven o’clock position from the bladder neck and distally around the area of the verumontanum) can contribute to an improved detection rate [42].

To enable accurate pathological assessment of surgical margins, biopsy sites (proximal/distal end) should be marked and sent together with clinical information to the pathologist. To obtain all relevant information, the collection, handling, and evaluation of biopsy specimen should follow the recommendations provided by the International Collaboration on Cancer Reporting (see Table 4.3) [34].

5.5. Imaging for diagnosis and staging

Radiological imaging of urethral carcinoma aims to assess local staging and to detect lymphatic and distant metastatic spread. In a recent multicentre study, the accuracy of cross-sectional imaging for clinical tumour and nodal staging predicting final pathological staging was found to be 72.9% and 70.6%, respectively [43]. Imaging work-up should include computed tomography (CT) of the chest, abdomen and pelvis for staging, including CT urography for urothelial evaluation. Magnetic resonance imaging (MRI) can be used to evaluate tumour location and size, as well as local tumour extent and presence of regional LN metastases, focusing in particular on inguinal and pelvic LNs [44-48].

For local staging, there is evidence that MRI is an accurate tool for monitoring tumour response to neoadjuvant chemoradiotherapy and evaluating the extent of local disease prior to exenterative surgery [49].

¹⁸F-Fluorodeoxglucose positron emission tomography/MRI has shown to improve the diagnostic evaluation in patients with metastatic disease [50].

5.6. Regional lymph nodes

In urethral carcinoma enlarged LNs often represent metastatic disease (~84% of patients) [51-53], which is in contrast to penile cancer where this is the case in ~41% of patients [54]. In men, lymphatics from the anterior urethra drain into the superficial- and deep inguinal LNs and, subsequently, to the pelvic (external, obturator and internal iliac) LNs. Conversely, lymphatic vessels of the posterior urethra drain into the pelvic LNs. In women, the lymph of the proximal third drains into the pelvic LN chains, whereas the distal two-thirds initially drain into the superficial- and deep inguinal nodes [55,56].

5.7. Summary of evidence and guidelines for diagnostic evaluation and staging