Performance of Ultrasound and MRI in Primary TUmor Staging

The majority of penile lesions are primary squamous cell tumors, although melanoma,23 basal cell carcinoma,24 sarcoma,25 and lymphoma26 have also been reported, and metastases are common enough to account for several case series,27,28 with bladder the commonest site of origin - either by hematogenous or urethral spread of transitional cell carcinoma.29,30 On MRI primary tumors are of intermediate signal: lower than the contents of the corpora (particularly when tumescent) but higher than the low signal layers of tunica albuginea and Buck's fascia (Figs. 4.8-4.11). On ultrasound squamous carcinomas are often heterogenous, but hypoechoic compared to the relatively echogenic tunica albuginea (Figs. 4.9-4.11). Although metastases have a variable appearance, they can usually be distinguished, like primary tumors, from the important normal structures.

Corpus Cavernosum Ultrasound

Fig. 4.8 T2-weighted axial MR of the glans showing a pT1G2 squamous cell carcinoma (white arrowheads). The underlying high signal spongiosus is a little compressed but not clearly invaded by the superficial tumor. This was correctly staged T1 on MRI

Fig. 4.9 Ulcerating lesion on the glans (white arrowheads, with a white arrow showing the ulcerated part), pT2 on histology and correctly called T2 on MRI (a) and ultrasound (b). CC marks corpus cavernosum, and S the spongiosal part of the glans. In contrast to Fig. 4.8, note that on MR the underlying high signal of the spongiosal tissue of the glans is altered by the tumor, although the tips of the cavernosa are well seen and not involved. The ultrasound confirms involvement of the spongiosal tissue of the glans but not the corpora cavernosa

Corpus Cavernosum Ultrasound

Fig. 4.10 (a) T3 tumor (white arrowheads) with invasion of the corpus spongiosum (CS), corpora cavernosum (L CC), and urethra. Note the fluid in the obstructed urethra (white arrow), a useful sign of involvement, seen on both MRI and ultrasound (b). For an image of more subtle invasion of the corpus cavernosum, see Fig. 4.12

Fig. 4.10 (a) T3 tumor (white arrowheads) with invasion of the corpus spongiosum (CS), corpora cavernosum (L CC), and urethra. Note the fluid in the obstructed urethra (white arrow), a useful sign of involvement, seen on both MRI and ultrasound (b). For an image of more subtle invasion of the corpus cavernosum, see Fig. 4.12

Corpus Cavernosum UltrasoundPenile Cancer UltrasoundPenile Cancer Ultrasound

Fig. 4.11 While most T3 tumors may be adequately assessed clinically, and excision margins confirmed by frozen section, imaging helps to show these rare cases of a skip lesion in the corpus cavernosum. In (a), two discrete tumor foci are seen in the corpora cavernosa on T2-weighted MRI (confirmed as discontinuous on histology). In a Doppler ultrasound image from another patient (b), a hypervascular nodule (white arrows) is seen discrete from the main tumor mass (arrowheads). A black arrow marks the normal cavernosal artery

Local staging has important implications for surgical planning and prognosis. The distinction between Ta and T1 disease is usually difficult because of the small size of the tumor, with Ta lesions often difficult to see at all on MRI. Imaging becomes important in the distinction between T1 and T2 disease: in other words, is one of the corpora invaded? As to which corpus is involved is also a relevant question, both for surgical planning and because disease-specific survival is considerably better with invasion of the spongiosum compared to cavernosum.31,32

The T3 classification (defined as involvement of prostate or urethra, TNM 2002) is also problematic. First, invasion of the prostate is uncommon without invasion of adjacent structures (i.e, T4) disease.32 Second, if the urethra is invaded, it is often near the meatus and may be treatable with penile-preserving surgery and has a good prognosis.32 This is reflected in the current survival rates for T2 and T3 disease, which are very similar.32

Several studies have examined the performance of ultrasound and MRI in the local staging of penile cancer. The first to assess staging accuracy was in 1994, when ultrasound without intracavernosal agents was compared to histopathology.9 It was difficult to distinguish between involvement of subepithelial connective tissue (T1) and corpus spongiosum (T2), because the tunica albuginea appeared much thinner over the spon-giosum compared to the cavernosum, and blended completely with subepithelial connective tissue in the glans. One case of invasion of the corpus cavernosum was correctly identified. The correlation between tumor 'thickness' on ultrasound and histology was excellent (R=0.94). No correlation was seen between grade and acoustic impedance.

A second study using ultrasound mainly of clinically T2 lesions found that it measured the size of tumor better than clinical examination and found that tumor was hyperechoic or hypoechoic in roughly equal numbers (Fig. 4.8), and that several cases of urethral invasion not suspected clinically were predicted by ultrasound.3 3 However, the main focus of this study was the estimation of tumor size, not stage.

MR imaging of tumors was first described in detail by Hricak et al. in 1988,3 but the first study to assess local staging accuracy was published in 1995.34 Nine patients were scanned without intracavernosal agents using a 0.5 T magnet and spin echo sequences around 5 mm in thickness, with T1 sequences pre and post contrast: considerably inferior to modern parameters. One tumor in the prepuce was not identified on MRI, and one focus of fibrosis was called tumor (this was also the clinical impression), but otherwise staging was correct. In one case urethral invasion was detected on MR when it was not suspected clinically. T2 sequences gave the best results in 5; in two contrast agents gave 'better delineation'.

Clinical findings, ultrasound, and MRI were compared in a study using a 1.5 T machine with T2 and T1 pre and post iv contrast, but not using intracavernosal agents to produce tumescence for the scan.2 This group found that tumor size was best determined by clinical examination, and that the positive clinical impression of T2 disease was correct in 6/6 patients. However, MRI predicted all cases of corpus cavernosum infiltration, while one was missed clinically and three missed on ultrasound. Urethral infiltration was seen in four patients and detected in three on MRI, two on ultrasound, and one clinically. Ultrasound and MRI had similar precision in predicting infiltration depth. The authors concluded that imaging (in particular with MRI) was useful when infiltration of the corpora 'could not be determined properly by clinical examination', and that MRI is useful for showing the proximal extent of disease and planning the extent of surgery.2 MR is likely better than ultrasound for very proximal lesions, which can be hard to see on ultrasound because the more proximal structures are deeper.16

The first study to describe the use ofMRI with intracavernosal agents for staging was published in 2004,18 again using a 1.5 T magnet and T2 and T1 pre and post contrast sequences, with 3-4 mm slice thickness. 10 mg of alprostadil intracavern-osally produced adequate tumescence in nine patients, but priapism in one. MRI correctly identified all cases of cavernosal invasion (five patients) but overestimated disease in three, with two T1 lesions called T2, and one T2 lesion called T3 due to apparent urethral involvement.

A larger study published in 2007 assessed MR after 10-20 mg alprostadil in 55 patients, with T2 and T1 pre and post contrast sequences.35 Although MR was described as 'excellent' and correctly predicted involvement of the corpus caverno-sum in two patients, it did overstage the disease, with six cases of T1 tumors called T2. This was ascribed to technical factors - poor response to prostaglandin, previous radiotherapy, motion artifact and infection - but it is likely that some of the error was also due to fundamental limits to the resolution of MRI and the difficulty in distinguishing abutment and bulge from true invasion. No cases of priapism were seen.

It is worth discussing the T staging in the glans in some detail, especially as it is the site of the majority of penile carcinomas.36 It was noted in an early ultrasound study that the tunica albuginea in the glans becomes difficult to see and blends with subepithelial connective tissue.3 Not only is staging therefore more difficult, but the finding of T2 disease has different implications, with glansectomy (partial or complete) the treatment of choice3 7,38 as opposed to partial or total penectomy when T2 disease involves the distal corpora cavernosa.39 While imaging may be relatively poor in early T2 disease in the glans, this may matter little if surgical margins are confirmed with frozen section analysis39; on the other hand prediction of cavernosal involvement seems excellent on modern MRI35 and is important for counseling the patient and surgical planning.

We have discussed the use of contrast in the section on MRI techniques, and reiterate here that although there are no publications formally comparing accuracy with and without contrast, we have not generally found it useful if intracavernosal agents are used to produce erection. While an early series without intracavernosal prostaglandin found that contrast 'provided a better delineation of tumor' in two patients,34 a more recent series using artificial erection, showed consistently better delineation of tumor and corpora cavernosa on T2-weighted images than T1 (including with contrast).18

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