The Role of Magnetic Resonance Imaging in the Local Staging of Penile Cancer

Transcription

1 european urology 51 (2007) available at journal homepage: Penile Cancer The Role of Magnetic Resonance Imaging in the Local Staging of Penile Cancer Oliver Kayes, Suks Minhas, Clare Allen, Chris Hare, Alex Freeman, David Ralph * St Peter s Hospital and The Institute of Urology, London, UK Article info Article history: Accepted November 3, 2006 Published online ahead of print on November 13, 2006 Keywords: MRI Penile cancer Staging Abstract Objectives: To assess the accuracy of magnetic resonance imaging (MRI) as a local staging technique in penile cancer and its role in selecting patients for conservative surgical management. Methods: Fifty-five men diagnosed with invasive penile carcinoma on biopsy were locally staged with the use of MRI. Prostaglandin E1 (alprostadil) was injected into the corpora to induce an artificial erection. Radiologic staging was compared against final histopathologic stage of the tumour. Sensitivity, specificity, and kappa agreement values were calculated for each tumour stage. Additionally, corpora cavernosa involvement was reviewed in 20 consecutive cases and suitability for conservative surgery assessed. Results: A good correlation between radiologic and histologic staging was achieved with an overall kappa value of 0.75 ( p < 0.001). Stagespecific sensitivities and specificities were calculated: T1 (85%; 83%), T2 (75%; 89%), and T3 (88%; 98%). MRI accurately predicted corpora cavernosa invasion in all cases of pathologically proven disease. These patients were selected to undergo partial penectomy. There were no complications using this imaging technique. Conclusions: This study demonstrates that penile MRI is highly accurate in the local staging of penile cancer. Associated improvements in surgical planning allow the provision of conservative surgical treatments over more radical procedures. # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. St Peter s Hospital, 235, Euston Road, London NW1 2BU, United Kingdom. address: dralph@andrology.co.uk (D. Ralph). 1. Introduction Penile malignancy is a rare tumour, comprising % of all cancers in the United Kingdom [1]. There is varied geographical incidence, with some areas of South America, Africa, and India reporting rates as high as 20% of all male cancers [2]. Squamous cell carcinoma (SCC) is the predominant malignant process, accounting for 95% of cases [3]. The primary tumour is located in the glans in 48% of /$ see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 1314 european urology 51 (2007) Fig. 1 Localised T2 tumour without corpora cavernosa involvement before and after glansectomy with skin grafting. cases, prepuce (21%), both glans and prepuce (9%), coronal sulcus (6%), with less than 2% isolated to the shaft. Thus, early tumours could be amenable to conservative surgery and penile reconstruction. Tumour size, site, and depth of the invasion help to determine the surgical management of the primary lesion. Small, distal, superficial lesions are more readily treated with the use of conservative surgical techniques [4]. Conservative approaches are favoured for cosmetic and functional results, thereby minimising the significant psychosexual morbidity associated with penile amputation (Fig. 1). However, it is imperative to ensure oncologic control with tumour-free margins. We have previously shown that conservative techniques, including wide local excision and partial/complete glansectomy, can be safely implemented in patients without corpora cavernosa involvement [5]. Current guidelines recommend the use of ultrasound (US) or magnetic resonance imaging (MRI), in combination with clinical examination to help delineate patients with corpora cavernosa (CC) infiltration [6]. However, experiences with ultrasound have proven that this technique is unreliable, especially in the presence of microscopic invasion [7]. MRI can offer a noninvasive means of staging both primary and locally recurrent penile malignancies. MRI affords increased soft tissue contrast and multiplanar capabilities, which generate optimal images of all penile compartments. When used in conjunction with artificial erection, MRI highlights the boundaries between corpus spongiosum and CC (high signal) from the tunica albuginea (low signal) seen as a black line on T2-weighted images (Fig. 2). We propose that MRI is an important adjunct in staging tumours prior to conservative surgery. However, there are few studies in the literature reporting the use of MRI in staging penile neoplasms [8 13]; the studies are limited by small patient numbers. The aims of this study were to assess the accuracy of MRI as a diagnostic tool in staging primary penile carcinoma and to review the implications for selecting patients to a conservative surgical approach. 2. Methods 2.1. Patients We recruited 55 men with a confirmed diagnosis of invasive SCC on preceding biopsy who presented to a single institution between 2000 and All patients were considered candidates for conservative surgical management on the basis of physical assessment. Patient consent was recorded and prostaglandin E1 (PGE1; alprostadil mg) was injected into the corpora to induce an artificial erection. The tumours were staged according to the TMN classification 2002 (Table 1) [14]. MRI images were analysed by two consultant radiologists establishing tumour site, local stage, and the presence or absence of corpora cavernosa infiltration. All cases were reported blind of the eventual pathologic stage of the resected specimen reported by a single pathologist. Representative images and specimens can be seen in Fig. 3. Stage-specific diagnostic tables (2 2) were constructed with sensitivity,

3 european urology 51 (2007) Table TMN classification of penile cancer Primary tumour Tx T0 Tis Ta T1 T2 T3 T4 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Noninvasive verrucous carcinoma Tumour invades subepithelial connective tissue Tumour invades corpus spongiosum or cavernosum Tumour invades urethra or prostate Tumour invades other adjacent structures 2.2. Magnetic resonance imaging All patients were scanned with the use of a Siemens (Erhlangen Germany) Magnetom 1.5T Vision MRI scanner. The penis was placed with the glans pointing superiorly, and a phased array body coil was placed upon pads to avoid compression artefact. The following sequences were used: (1) sagittal T2 TSE 15 4 mm TR 5935 TE 132, matrix 256; field of view (FOV) included penis to back of prostate; (2) coronal T2 TSE 15 4 mm TR 5935 TE 132, matrix 256; FOV included penis, scrotum, and inguinal regions; (3) axial dual echo PD TSE 5 mm TR 5466 TE22, matrix 256; FOV included penis to back of rectum and edges of bony pelvis laterally; (4) coronal T1 fat sat 5 mm TR 1930 TE 12, matrix 256, FOV as coronal T2; (5) postgadolinium contrast 10 ml intravenously (Magnevist). The anatomic boundaries are demonstrated in Fig Results Fig. 2 (A) Magnetic resonance imaging (MRI) of the normal erect penis. Transverse section through the coporal heads demonstrating the urethra enclosed in corpus spongiosum (1b); corpora cavernosa (2a) with cavernosal arteries (blue arrows) and proximal glans/corona (3). (B and C) MRI of the normal erect penis. Sagittal and coronal sections demonstrating the anatomic boundaries separated by the black line of tunica albuginea (orange arrows). Fifty-five men, mean age 61 yr (32 85), were successfully included in this study. All patients were diagnosed with invasive SCC on penile biopsy, entered into the imaging protocol, and stratified to treatment. Overall MRI staging corresponded to T1 (23), T2 (24), and T3 (8). Histologic staging was recorded as T1 (19), T2 (28), and T3 (8). This information is illustrated in Table 2, demonstrating the number of cases that were correctly staged using MRI. The cases of nonaccordance, for which MRI understaged or overstaged the primary cancer, are highlighted. Overall, kappa value of agreement was calculated as 0.75 ( ), which is statistically significant p < at 95% confidence interval. MRI specificity, and kappa value of agreement calculated with the use of statistical software (StatsDirect). A subset of 20 consecutive cases were analysed for CC involvement and correlation on pathologic review. Patients with confirmed CC involvement on MRI were selected to be treated with a partial penectomy. All other cases underwent a conservative procedure, either wide local excision or partial/ complete glansectomy. Borderline cases of CC involvement received additional intraoperative frozen section assessment to confirm clear surgical margins. Table 2 Staging confirmation by magnetic resonance imaging (MRI) versus histopathologic diagnosis Histology T1 T2 T3 Total MRI T T T Total

4 1316 european urology 51 (2007) Fig. 3 (A) Sagittal TSE T2 penis and histologic section from the same patient. Stage T3 tumour involves erectile tissue of glans (blue arrows), tunica albuginea (white arrow), and urethra (green arrow). (B) Coronal TSE PD penis and histologic section from same patient. Superficial T1 warty lesion of glans tip (blue arrows), glans erectile tissue (green arrows), and prepuce (white arrows). Corpora cavernosal tissue (orange arrow) highlighted is not involved. This lesion is clearly amenable to conservative resection. overstaged tumours in seven cases (13%) and understaged in three cases (6%). Diagnostic tables (2 2) were constructed and from these data the sensitivity, specificity, and kappa value were calculated for each tumour stage. The results of this analysis are demonstrated in Table 3. Table 4 displays data regarding operative outcome compared with MRI and pathologic findings, especially with respect to CC infiltration. We can observe from these data that MRI is highly accurate at delineating CC invasion from cases without CC involvement (19 of 20 cases). Also, in the presence of borderline cases, frozen section analysis supports radiologic findings and can be used to confirm tumour clearance. Thus, it is possible to stratify patients to conservative surgery with greater assurance, thereby sparing these men from more radical amputation. It is noted that, in one case, it was impossible to determine the depth of invasion of the Table 3 Magnetic resonance imaging sensitivity, specificity, and kappa agreement (standard errors) in local staging of penile carcinoma Sensitivity Specificity Kappa (K) p value T1 T2 T3 89% (69 98) 83% (67 94) 0.69 ( ) < % (55 89) 89% (71 97) 0.64 ( ) < % (47 99) 98% (88 100) 0.85 ( ) <0.001

5 european urology 51 (2007) Table 4 Review of 20 consecutive cases to assess the correlation between magnetic resonance imaging (MRI) and pathologic staging: MRI prediction of corpora cavernosa infiltration and subsequent surgical approach Patient Pathology stage Radiology stage Cavernosal involvement Surgery Frozen Section * Result No Glansectomy Yes Negative No Glansectomy No N/A No Glansectomy Yes Negative No Glansectomy No N/A No Glansectomy No N/A Yes Partial penectomy Specimen Positive No Glansectomy Yes Negative No Local No N/A No Partial glansectomy Yes Negative No Glansectomy Yes Negative No Glansectomy No N/A No Partial glansectomy Yes Negative No Glansectomy Yes Negative No Glansectomy Yes Negative No Glansectomy Yes Negative Yes Partial penectomy Specimen Positive No Glansectomy Yes Negative No Glansectomy No N/A No Glansectomy Yes Negative No Glansectomy Yes Negative * Frozen section was utilised in borderline cases. tumour because the patient failed to respond to the intracavernosal aprostadil injection. This problem highlights the importance of artificial erection to the scanning protocol to fully demonstrate the boundaries between penile compartments. Additionally, there were no incidences of priapism. 4. Discussion Penile amputation can cause significant psychosexual morbidity. Conservative surgical techniques including wide local excision and glans excision have been introduced, which aim to preserve erectile and voiding function, whilst minimising psychological morbidity. MRI of the penis appears to be a potential staging tool in the assessment of tumours amenable to such surgery. Lont et al [8] demonstrated clearly in their study that physical examination is accurate at detecting CC infiltration but that the role of MRI needed further elucidation. It is noted that ultrasound was unpredictable at determining the depth of invasion when compared against pathologic sections. We propose that MRI with PGE1 injection offers a sophisticated method of mapping tumours that are not easily palpated clinically and of highlighting potential areas of microinvasion. Information gained from each MRI scan can help to direct surgical techniques, to incorporate focused frozen section analysis of suspicious areas, thus promoting phallus-preserving surgery. Conversely, we also observed that MRI was extremely accurate in delineating superficial tumours (T1 + T2 spongiosum), thus avoiding an intraoperative frozen section in these cases, which impacted operative times and cost benefits. The two largest studies [10,13] reviewing the accuracy of MRI in staging penile cancer are limited by low patient numbers (nine cases in each study). We have expanded on the findings from these preliminary studies, demonstrating a strong correlation between radiologic and pathologic staging (overall kappa = 0.75) and accuracy in selecting patients for conservative surgery. Intracavernosal PGE1 (alprostadil) injection with artificial erection appears to accentuate the boundary between the tunica albuginea and the CC on T2-weighted images (Fig. 2). This accentuation appears to be critical in the accurate local staging of penile tumours and was omitted from the previous study by the Dutch group [8]. We advocate the safe use of this methodology, as supported by the lack of adverse effects in our series. It is important to consider dosing limitations, which are dependant on the patient s age, preexisting erectile dysfunction, and tumour size to avoid the onset of priapism. This study has demonstrated that MRI is highly sensitive and specific for local staging of penile cancer (Fig. 3). Importantly, we have also demonstrated that MRI is accurate at predicting CC

6 1318 european urology 51 (2007) involvement (positive predictive value: 100%; negative predictive value: 100%) and thus is a reliable tool for selecting patients for conservative surgery. We noted that 10 cases (18%) were inaccurately staged by our radiologist colleagues. However, these errors did not impact on clinical decision making and surgical planning, possibly because of the accuracy of MRI for delineating CC infiltration. These errors seemed to arise because of a series of core, technical problems including lack of erection as discussed previously, motion artefact, previous radiotherapy to the penis, and associated infection. In the presence of one or more of these factors, it is prudent to rely more strongly on intraoperative frozen section. MRI offers clear, multiplanar images with superior soft tissue resolution, enhancing surgical planning with respect to the surgical excision margins. The high sensitivity and specificity allows reliable surgical planning when attempting organ-preserving techniques. MRI is not a replacement for standard histologic staging but is a dependable adjunct when considering surgical options for men with penile cancer. 5. Conclusions This study has shown penile MRI to be a reliable and highly accurate imaging modality for local staging of primary penile cancer. Patients can be more confidently counselled with regards to conservative surgical treatments and outcomes. References [1] Burgers JK, Bandalament RA, Drago JR. Penile cancer. Clinical presentation, diagnosis and staging. Urol Clin North Am 1992;19: [2] Narayana AS, Olney LE, Loening SA, et al. Carcinoma of the penis: analysis of 219 cases. Cancer 1982;49: [3] Cubilla AL, Barreto J, Caberello C, et al. Pathological features of epidermoid carcinoma of the penis. Am J Surg Pathol 1993;17: [4] Davis JW, Schellhammer PF, Schlossberg SM. Conservative surgical therapy for penile and urethral carcinoma. Urology 1999;53: [5] Minhas S, Kayes O, Hegarty P, et al. What surgical resection margins are required to achieve oncological control in men with primary penile cancer? BJU Int 2005;96: [6] Solsona E, Algaba F, Horenblas S, et al. European Association of Urology. EAU Guidelines on Penile Cancer. Eur Urol 2004;46:1 8. [7] Horenblas S, Kroger R, Gallee MP, et al. Ultrasound in squamous cell carcinoma of the penis; a useful addition to clinical staging? A comparison of ultrasound with histopathology. Urology 1994;43: [8] Lont AP, Besnard AP, Gallee MP, et al. A comparison of physical examination and imaging in determining the extent of primary penile carcinoma. BJU Int 2003;91: [9] Lau TN, Wakeley CJ, Goddard P. Magnetic resonance imaging of penile metastases: a report on five cases. Australas Radiol 1999;43: [10] de Kerviler E, Ollier P, Desgrandchamps F, et al. Magnetic resonance imaging in patients with penile carcinoma. Br J Radiol 1995;68: [11] Kawada T, Hashimoto K, Tokunaga T, et al. Two cases of penile cancer: magnetic resonance imaging in the evaluation of tumour extension. J Urol 1994;152: [12] Hricak H, Marotti M, Gilbert TJ, et al. Normal penile anatomy and abnormal penile conditions: evaluation with MR imaging. Radiology 1998;169: [13] Scardino E, Villa G, Bonomo G, et al. Magnetic resonance imaging combined with artificial erection for local staging of penile cancer. Urology 2004;63: [14] American Joint Committee on Cancer. AJCC cancer staging manual. 6th ed. New York: Springer; p Editorial Comment Giorgio Pizzocaro, Milan, Italy pizzocaro@iol.it This is the first large series on magnetic resonance imaging (MRI) in the local staging of penile cancer although the first paper on nine cases was published in 1995 [1]. The fact is that in Great Britain patients with penile cancer are being referred to a few specialised centres with the advantage of increased experience. Recently, the statement that partial or total amputation, or emasculation according to the tumor extent, can be considered to be standard therapies for category T1G3 and T 2 penile cancer [2] has been challenged. For instance, Minhas et al [3] published data on 51 men with penile cancer treated between May 2000 and December 2004; 9 had a wide local excision, 26 had glansectomy, and 16 had partial amputation. Both deep and skin surgical margins were examined. Three patients only had positive surgical margins and two others developed a local recurrence. All five were treated successfully with further surgery.

7 european urology 51 (2007) Finally, Romero et al [4] interviewed 18 patients (median age, 52 yr) who had undergone partial penectomy; the medium penile length after surgery was 4 cm in the flaccid state. Ten patients reported postoperative erectile function that could allow intercourse, but the main reason for not resuming sexual activity was the feeling of shame and only six continued sexual activity. We need both good preoperative imaging and a careful examination of surgical margins to perform radical and less aggressive surgery for cathegory T1 and T2 squamous cell carcinoma of the glans penis. MRI with injection of prostaglandin E 1 can be of help in predicting corpora cavernosa invasion in most cases. References [1] de Kerviler E, Ollier P, Desgrandchamps F, et al. Magnetic resonance imaging in patients with penile carcinoma. Br J Radiol 1995;68: [2] Solsona E, Algaba F, Horenblas S, Pizzocaro G, Windahl T. European Association of Urology. EAU guidelines on penile cancer. Eur Urol 2004;46:1 8. [3] Minhas S, Kayes O, Hegarty P, Kumar P, Freeman A, Ralph D. What surgical resection margins are required to achieve oncological control in men with primary penile cancer? BJU Int 2005;96: [4] Romero FR, Pereira Dos Santos R, Romero K, et al. Sexual function after partial penectomy for penile cancer. Urology 2005;66: