Reconstructive Surgery for Invasive Squamous Carcinoma of the Glans Penis

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1 european urology 52 (2007) available at journal homepage: Penile Cancer Reconstructive Surgery for Invasive Squamous Carcinoma of the Glans Penis Yuko Smith a, Paul Hadway a, Olaf Biedrzycki b, Matthew J.A. Perry a, Catherine Corbishley b, Nicholas A. Watkin a, * a Department of Urology, St George s Hospital, London, United Kingdom b Department of Cellular Pathology, St George s Hospital, London, United Kingdom Article info Article history: Accepted February 13, 2007 Published online ahead of print on February 20, 2007 Keywords: Penis Reconstructive surgery Squamous cell carcinoma Abstract Objectives: We present medium-term outcome data for patients with invasive penile cancer treated with glansectomy and reconstruction with a split-thickness skin graft. Methods: A series of consecutive patients referred with penile malignancies over a 6-yr period were analyzed prospectively. A dedicated histopathologist reviewed all the specimens. After clinical staging, patients with tumours confined to the glans were offered glansectomy. Results: A total of 72 patients (32% of patients, 31% of procedures) underwent glansectomy for penile carcinoma. Of these, 65 patients were new diagnoses and seven were recurrences after radiotherapy. The mean follow-up period was 27 mo (range: 4 68 mo). There have been three late local recurrences (4%). Conclusion: Glansectomy appears to be an oncologically safe and effective procedure for patients with glans-confined squamous cell tumours. It preserves maximum phallic length and results in a very satisfactory cosmetic penile appearance after reconstruction. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, St James Wing, St George s Hospital, Blackshaw Road, London SW17 0QT, UK. Tel ; Fax: address: nick.watkin@stgeorges.nhs.uk (N.A. Watkin). 1. Introduction Penile cancer is a rare malignancy in Western countries, with an incidence of less than one in 100,000. In the United Kingdom there are around 360 new cases per year, and the development of supraregional networks has meant that these patients are now being managed in a few specialist centres. This has enabled urologists and oncologists in the United Kingdom to develop and evaluate new treatments in a way that has not previously been possible [1]. Until recently, partial or radical penectomy was the mainstay of surgical treatment for penile cancer, but this is associated with considerable psychosexual morbidity [2]. These operations were based on /$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 1180 european urology 52 (2007) the understanding that a 2-cm macroscopic margin is necessary for adequate oncological control. Recent evidence, however, has suggested that margins of only a few millimetres may be adequate for most tumours, which has led to increasing interest in penile-preserving procedures [3,4]. Current EAU guidelines on the management of penile cancer strongly recommend a penile-preserving approach for patients with Ta T1 G1 G2 tumours who can commit to a regular surveillance programme, and the guidelines suggest that it may also be an option in very selected patients with T1 G3 and T < 2 disease whose tumours occupy less than 50% of the glans. Alternative recommended procedures include laser, local excision with reconstruction, and brachytherapy [5]. In a previous paper we reported early outcome data for invasive penile cancer treated with a variety of penile-preserving techniques, including partial glansectomy with or without reconstruction, glansectomy with reconstruction, and glansectomy and distal corporectomy with reconstruction [6]. Here we present medium-term data for the largest group of patients, those with tumours confined to the glans who have been treated with glansectomy. 2. Methods We prospectively analyzed consecutive patients with invasive penile cancer treated with glansectomy over a 6-yr period. Patients were referred from a supraregional network. All cases were reviewed in a specialist multidisciplinary team meeting by a single histopathologist and staged according to the revised 2002 American Joint Committee on cancer TNM staging system. Patients who were assessed to have squamous cell tumours limited to the glans (ie, T1 and T2 tumours of the Fig. 2 Circumferential incision down to Buck s fascia. The glans is dissected off the corporal heads. corpus spongiosus) on clinical examination were offered glansectomy with split-thickness skin graft reconstruction. Patients who were up-staged with frozen section and underwent glansectomy and distal corporectomy with reconstruction were excluded. Magnetic resonance imaging of the penis was performed to assess corpora cavernosal invasion in patients with equivocal examination findings. Glansectomy with split-thickness skin graft reconstruction was performed as described previously [6] and illustrated in Figs In brief, a subcoronal circumferential incision is made in the shaft skin, down to the level of Buck s fascia. The glans is then dissected off the corporal heads and an end urethrostomy is created. The shaft skin is sutured approximately 2 cm from the tip, and a split-thickness skin graft taken from the lateral thigh is used to cover the corporal heads. The graft is secured with quilting sutures and circumferential absorbable sutures. A urethral catheter is inserted at the end of the procedure. The patient is bed-rested for 4 d and has a Fig. 1 Glans tumour. Fig. 3 The glans has been excised. The corporal heads are exposed.

3 european urology 52 (2007) Table 1 Procedures Procedure No. of procedures Glans resurfacing 18 (8%) Circumcision (done as part of another 36 (16%) procedure in some) Wide local excision with primary closure 39 (17%) Partial glansectomy and reconstruction 8 (4%) Glansectomy and reconstruction 72 (31%) Glansectomy, distal corporectomy, 26 (11%) and reconstruction Partial penectomy 11 (5%) Radical penectomy 19 (8%) Total of 229 procedures on 222 patients. Fig. 4 A split-thickness skin graft has been quilted onto the corporal heads to form a neoglans. Table 2 Tumour stage and grade G1 (%) G2 (%) G3 (%) Total T1 (%) 12 (17%) 13 (18%) 10 (14%) 35 (49%) T2 (%) 5 (7%) 18 (25%) 14 (19%) 37 (51%) Total 17 (24%) 31 (43%) 24 (33%) 72 urethral catheter for 5 d. Frozen-section analysis of margins was used in all patients initially but is now used in cases where complete macroscopic excision is difficult to ascertain. The corporal heads are excised and reconstructed in patients with positive frozen-section margins. Regional lymph nodes were assessed by clinical examination aided by ultrasound with or without fine-needle aspiration cytology and CT scan, as appropriate. Since 2004, patients with impalpable groin nodes have undergone dynamic sentinel lymph node biopsy as an additional staging tool, usually at the time of penile reconstruction. 3. Results Fig. 5 Postoperative appearance at 5 wk. Of the 245 patients referred to our unit for the management of penile cancer, 222 patients required penile surgery. Of these, 178 patients had tumours that were at least T1, and the procedures performed are listed in Table 1. Seventy-two patients (32% of patients, 31% of procedures) were treated with glansectomy and skin graft reconstruction for penile squamous cell carcinoma, which comprises the largest group. The mean age was 60 yr (range: yr). Seventeen (24%) had grade 1 tumours, 31 (43%) had grade 2, and 24 (33%) had grade 3. Of the 72 cases, 35 (49%) had T1 disease and 37 (51%) had T2 disease. The clinical staging is shown in Table 2. Nine tumours had verruciform features, and 10 had basaloid features. The nearest resection margins of the specimens are listed in Table 3. This data was not available in all patients prior to introduction of minimum cancer dataset in Thirty-seven of 61 patients (61%) had a nearest resection margin of 5 mm or less, including six patients with positive resection margins. Of these, four patients were observed (for 12, 13, 19, and 23 mo) with no evidence of recurrence. Two patients were observed briefly but showed evidence of recurrence within a few weeks and underwent local excision with no further problems. Table 3 Distance to nearest excision margin (n = 61) Nearest margin (mm) No. of specimens Margin involved 6 < >11 10

4 1182 european urology 52 (2007) The mean follow-up period was 27 mo (range: 4 68 mo). Forty-four patients have been followed up for 2 yr or more (59 patients 1 yr). There have been three (4%) late local recurrences during this period. Two of these recurrences were in patients with G1T1 verrucous carcinomas, with clear margins at initial resection, and occurred at 19 and 28 mo. We presume that this may have been due to an implantation phenomenon. The third recurrence was at 4 mo in a patient with basaloid G3T2 tumour with clear margins but significant lymphovascular invasion, including tumour in vessels in the corpus spongiosus. All three patients have been treated with wide local excision, however, the third patient is undergoing chemotherapy in view of his high-risk disease. Ten patients had lymph node involvement at the time of diagnosis, five of these had impalpable disease as detected by sentinel lymph node biopsy. Two patients have died of unrelated conditions. Two patients with metastatic disease have died, without evidence of local recurrence. Early complications include two patients who had partial graft loss and required regrafting. Late procedure-related complications include one patient with graft overgrowth of the external urethral meatus; he was unable to tolerate self-dilatation and required formal urethral dilatation. 4. Discussion In 2001 a questionnaire survey was completed by 289 urologists and 237 oncologists in the United Kingdom to assess their management of localized penile cancer; the study found that almost 30% of urologists and one oncologist preferred partial or total amputation for even a small distal lesion on the glans penis [7]. However, 80% of penile carcinomas involve the glans, coronal sulcus, or prepuce and may therefore be amenable to penile-preserving rather than amputative surgery. Another U.K. study conducted prior to the introduction of supraregional networks found that most urological consultants registered only one or two patients with a new diagnosis of penile cancer over a 14-mo period [8]. This has meant that it was difficult for individual surgeons to gain a broad experience of managing this condition. Management of penile cancer has therefore been variable. To improve care, the National Institute of Clinical Excellence recommended the formation of specialist penile cancer multidisciplinary teams in the United Kingdom serving a population of over 4 million people. Since its implementation, we now see 60 to 80 patients per year at our institution. Conventional treatment for penile carcinoma has entailed partial or radical penectomy or radiotherapy. Radiotherapy is well established in the treatment of penile carcinoma and may be given as external beam radiotherapy or brachytherapy. Although radiotherapy has the advantage of preserving the penis, local recurrence rates are higher than with amputative surgery. External beam radiotherapy, in particular, has been associated with recurrence rates of 40 50%, although salvage surgery can be performed in many cases [9]. Brachytherapy appears to achieve better local control rates than external beam radiotherapy. In a series of 30 patients treated with brachytherapy, Crook et al. [10] reported only four local failures (13%), two of whom had T1 or T2 tumours. The penile-preservation rate in this group was 25 of 28 patients (89%), as one additional patient required partial penectomy for radiation necrosis [10]. Treatment with both external beam radiotherapy and brachytherapy may be limited by acute radiation reactions, and patients may develop distal urethral adhesions and urethritis in the short term. Meatal stenosis, urethral strictures, fibrosis, pigmentation, telangectasia, and late radiation necrosis may result in the longer term and can necessitate amputative surgery [9,10]. Partial and total penectomy achieves good local control, although these procedures are associated with significant psychosexual morbidity. A study of men who had been treated for penile cancer with a variety of methods found that seven of 25 men would risk lower long-term survival to increase the chance of remaining sexually potent [2]. Amputative surgery has been based on traditional teaching that a 2-cm margin is necessary for adequate surgical control. This figure is not supported by firm evidence, however, and has been challenged by several groups. Hoffman et al. [3] examined pathological resection margins of patients undergoing partial or total penectomy and found no local recurrences in any of their 14 patients, despite seven having resection margins <10 mm. Average follow-up was 33 mo for patients who had partial penectomy and 40 mo for the total penectomy group [3]. Another group studied resection margins in 51 patients with penile squamous carcinoma treated with a variety of techniques; 49 margins measured within 10 mm of the tumour edge and 92 within a margin of <20 mm [4]. The recurrence rate was 4% over a median follow-up of 26 mo, and the authors concluded that resection margins of a few millimetres may be sufficient to offer adequate oncological control [4]. Interest has therefore been focused on organ-preserving procedures, including laser and more limited surgical resection, with or without reconstruction.

5 european urology 52 (2007) Laser treatment has most commonly been described for the treatment of carcinoma in situ. Some groups, however, have also used the technique for the treatment of invasive disease. Carbon dioxide laser is used in place of a scalpel to excise tumour, thus obtaining a histological specimen, whereas neodymium:yag laser is used to destroy tumours by coagulation. The latter technique does not produce a histological specimen and therefore has the potential to understage tumours. An early series of 47 men who were treated with carbon dioxide laser for very superficial disease (mean depth: 1.5 mm) suggested good disease control [11]. However, in a more recent series of 67 men treated with combined carbon dioxide and neodymium:yag laser, 13 patients (19%) had disease recurrence, including three with multiple recurrences [12]. In three patients the recurrence was of a higher grade and/or stage than the original tumour. Recurrence was seen in three of 21 patients (14%) with CIS; six of 24 (25%) with pt1; three of 19 (25%) with pt2; and one of two (50%) with pt3 disease. Thus, although with close surveillance use of a laser appears to be an effective treatment for pre-invasive and very superficial disease, it is associated with a high recurrence rate in invasive disease (10 of 45, 22%) [12]. Initial experience with conservative surgery had suggested that local control is significantly worse ( p < 0.05) with penile preservation than with amputation. Lindegaard et al. [13] analyzed 63 patients who were candidates for primary penile-preserving surgery according to EBU criteria. Twenty-six patients underwent partial or total amputation, and 37 were treated with some form of penis-conserving therapy. They found that local control rates were significantly lower for conservative therapy than amputation (5-yr actuarial control rates of 69% and 100%, respectively, for T1 tumours), although overall survival was not affected as most patients could be salvaged with radical surgery [13]. Bissada et al. [14] reported 30 patients who were treated with unconventional tailored surgical excisions ; the authors did not describe the surgical techniques other than to say that it entailed complete primary excision of the tumour with preservation of uninvolved penile structures. Over a follow-up of mo, 21 patients were disease free, three patients had local recurrences that were successfully treated with further resection, and one patient had died of the disease [14]. In our previous paper, we described one local recurrence in a patient who had undergone partial glansectomy, but not in any patient who had undergone total glans excision. This was felt to be due to tumour growth in surrounding unstable epithelium [6]. With additional patients and a longer follow-up, we have found three local recurrences in patients who have been treated by glansectomy. Because the above-cited papers did not include descriptions of the nature of surgery, it is possible that their higher recurrence rates reflect field change in the remaining glans tissue. Frozen-section analysis of resection margins is advisable in patients undergoing penile-preserving surgery to ensure complete resection of the tumour. Given the observed spreading pattern of penile tumours [15], Algaba et al. suggested that tissue from the urethral and corporal margins would be most useful [16]. In this paper we have described 72 patients who underwent glansectomy with reconstruction for glans-confined penile squamous cell cancer. Local disease control has been excellent, with a 6% recurrence rate, despite 24 patients (33%) having high-grade tumours and 37 (51%) with T2 disease. Radiotherapy or amputative treatment with at least partial penectomy is currently considered as standard in these patients, but glansectomy has the advantage of excellent cosmetic results with good phallic length preservation with comparable recurrence rates. Although sexual function has not been formally assessed, the majority of patients who were sexually active preoperatively have been able to continue sexual intercourse after the glansectomy. Operating time for glansectomy with reconstruction is around 75 min, compared to 40 min for partial penectomy. Despite slightly longer operating times, reconstructive surgery with a split-thickness skin graft has been well tolerated by our patients (median age: 60 yr, range: yr), with only 11 of 222 patients (5%) requiring or electing for partial penectomy and 19 (8%) needing radical penectomy. Austoni et al. was one of the first groups to emphasize the anatomical distinction between the corpora cavernosa and corpus spongiosus and to propose glansectomy as an effective treatment for glans-confined penile cancer [17]. Subsequently, a few other groups have reported small series of patients treated with glansectomy. Davis et al. [18] described three patients who had undergone glansectomy for the treatment of verrucous carcinoma, angiosarcoma, and malignant melanoma. There was no local recurrence in any of these patients, although the patient with angiosarcoma did develop distant metastasis. All patients were able to void normally, two patients had adequate erections, and the other patient was able to have sexual intercourse by using a vacuum erection device [18]. Hatzichristou et al. [19] described seven patients with Buschke-Löwenstein tumours who were treated with glansectomy without skin graft

6 1184 european urology 52 (2007) reconstruction. One patient developed local recurrence at 3 mo and was successfully treated by partial penectomy. All patients were disease free at 18- to 65-mo follow-up with acceptable aesthetic results, and they expressed satisfaction with their sex lives [19]. As management of the primary tumour has moved towards conservative surgery, interest has grown in reducing the morbidity and extent of lymph node dissections. The presence of lymph node metastases is the most important prognostic factor in patients with penile cancer. Because only 20% of patients with clinically impalpable nodes will have occult metastases, prophylactic lymphadenectomy would subject the majority of these patients to unnecessary morbidity. Dynamic sentinel lymph node biopsy is a diagnostic technique that allows targeting of completion lymphadenectomy to patients with occult metastases, as detected by the procedure [20]. Since November 2004, patients in our unit with a greater than G2T1 primary tumour have been offered dynamic sentinel lymph node biopsy. The technique has detected occult metastases in five patients in our glansectomy group. A 10-yr experience from the Netherlands Cancer Institute has shown 5-yr disease-specific survival of 96% for patients with negative sentinel nodes, compared to 66% for those with positive sentinel nodes [20]. They also reported that immediate dissection of clinically occult lymph node metastases, detected by sentinel lymph node biopsy, appears to confer a significant improvement in survival when compared to lymphadenectomy when lymph nodes become palpable [21]. 5. Conclusion As our understanding of penile cancer increases, it is becoming increasingly apparent that the traditionally advocated resection margin has resulted in over treatment of many patients. With close postoperative observation, glansectomy is an ideal treatment for patients with T1 and T2 penile carcinoma confined to the corpus spongiosus. Glansectomy allows preservation of penile length and satisfactory cosmetic appearance, without compromising local cancer control. Although longer follow-up is needed, based on our medium-term findings margins of a few millimetres appear to be sufficient. Conflicts of interest The authors have nothing to disclose. Acknowledgements We thank Aivar Bracka, who originally described the technique to the senior author. References [1] Singh R, James ND, Watkin NA. Future development of penile cancer services in the UK. BJU Int 2004;94: [2] Opjordsmoen S, Fossa SD. Quality of life in patients treated for penile cancer: a follow-up study. Br J Urol 1994;74: [3] Hoffman MA, Renshaw AA, Loughlin KR. Squamous cell carcinoma of the penis and microscopic pathologic margins: How much margin is needed for local cure? Cancer 1999;85: [4] 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: [5] Solsona E, Algaba F, Horenblas S, Pizzocaro G, Windahl T. EAU guidelines on penile cancer. Eur Urol 2004;46:1 8. [6] Pietrzak P, Corbishley C, Watkin N. Organ-sparing surgery for invasive penile cancer: early follow-up data. BJU Int 2004;94: [7] Harden SV, Tan LT. Treatment of localized carcinoma of the penis: a survey of current practice in the UK. Clin Oncol (R Coll Radiol) 2001;13: [8] Ritchie AW, Foster PW, Fowler S, for the BAUS Section of Oncology. Penile cancer in the UK: clinical presentation and outcome in 1998/99. BJU Int 2004;94: [9] Azrif M, Logue JP, Swindell R, Cowan RA, Wylie JP, Livsey JE. External-beam radiotherapy in T1 2 N0 penile carcinoma. Clin Oncol (R Coll Radiol) 2006;18: [10] Crook J, Grimard L, Tsihlias J, Morash C, Panzarella T. Interstitial brachytherapy for penile cancer: an alternative to amputation. J Urol 2002;167: [11] Bandieramonte G, Lepera P, Marchesini R, Andreola S, Pizzocaro G. Laser microsurgery for superficial lesions of the penis. J Urol 1987;138: [12] Windahl T, Andersson SO. Combined laser treatment for penile carcinoma: results after long-term follow up. J Urol 2003;169: [13] Lindegaard JC, Nielsen OS, Lundbeck FA, Mamsen A, Studstrup HN, von der Maase H. A retrospective analysis of 82 cases of cancer of the penis. Br J Urol 1996;77: [14] Bissada NK, Yakout HH, Fahmy WE, et al. Multi-institutional long-term experience with conservative surgery for invasive penile carcinoma. J Urol 2003;169: [15] Velázquez EF, Soskin A, Bock A, Codas R, Barreto JE, Cubilla AL. Positive resection margins in partial penectomies: sites of involvement and proposal of local routes of spread of penile squamous cell carcinoma. Am J Surg Pathol 2004;28: [16] Algaba F, Arce Y, López-Beltán A, Montironi R, Mikuz G, Bono AV. Intraoperative frozen section diagnosis in urological oncology. Eur Urol 2005;47:

7 european urology 52 (2007) [17] Austoni E, Fenice O, Kartalas Goumas Y, Colombo F, Mantovani F, Pisani E. New trends in the surgical treatment of penile carcinoma. Arch Ital Urol Androl 1996;68:163 8 (In Italian; abstract only). [18] Davis JW, Schellhammer PF, Schlossberg SM. Conservative surgical therapy for penile and urethral carcinoma. Urology 1999;53: [19] Hatzichristou DG, Apostolidis A, Tzortzis V, Hatzimouratidis K, Ioannides E, Yannakoyorgos K. Glansectomy: an alternative surgical treatment for Buschke-Löwenstein tumors of the penis. Urology 2001;57: [20] Kroon BK, Horenblas S, Meinhardt W, et al. Dynamic sentinel node biopsy in penile carcinoma: an evaluation of 10 years experience. Eur Urol 2005;47: [21] Kroon BK, Horenblas S, Lont AP, Tanis PJ, Gallee MP, Nieweg OE. Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases. J Urol 2005;173: Editorial Comment on: Reconstructive Surgery for Invasive Squamous Carcinoma of the Glans Penis Giorgio Pizzocaro Università degli Studi di Milano, Ospedale S. Giuseppe, Clinica Urologica, Via S. Vittore 12, Milan, Italy pizzocaro@iol.it The importance of this paper [1] is not only the report of 72 patients with penile cancer limited to the glans penis (49% T1, 51% T2) treated with glansectomy and contemporary split-thickness skin graft reconstruction with only three local recurrences among 222 treated patients of whom only 30 had partial or total amputations, but also the fact that, following two recent national questionnaire surveys in the United Kingdom, it was realised that most urological consultants registered only 1 or 2 patients with a new diagnosis of penile cancer over a 14 month period [2] and that 30% of urologist preferred penile amputation for even a small distal lesion of the glans penis [3]. Therefore, a large regional network of special penile cancer multidisciplinary teams serving populations of over 4 million people was activated in the United Kingdom. Since that implementation in 2001, each of the six to eight teams was to see men with penile cancer per year. At the present time, five multidisciplinary teams are actively working in the United Kingdom. In the other countries, men with penile cancer are still being referred to specialised cancer centres, which recruit hundreds of patients in few decades [4], and recently, cooperative groups have spontaneously organised to collect data on hundreds of patients to make retrospective analyses [5]. In addition, concentrating patients with penile cancer in a few multidisciplinary institutions will also probably allow the initiation of randomised trials for penile cancer in the near future. References [1] Smith Y, Hadway P, Biedrzycki O, et al. Reconstructive surgery for invasive squamous carcinoma of the glans penis. Eur Urol 2007;52: [2] Ritchie AW, Foster PW, Fowler S, BAUS Section of Oncology. Penile cancer in the UK: clinical presentation and outcome in 1998/99. BJU Int 2004;94: [3] Harden SV, Tan LT. Treatment of localized carcinoma of the penis: a survey of current practice in the UK. Clin Oncol (R Coll Radiol) 2001;13: [4] Leijte JAP, Kroon BK, Valdès Olmos RA, Nieweg O, Horenblas S. Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma. Eur Urol 2007;52: [5] Ficarra V, Zattoni F, Artibani W, et al. Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis. J Urol 2006;175: DOI: /j.eururo DOI of original article: /j.eururo