Penile Sparing Surgery for Penile Cancer: A Multicenter International Retrospective Cohort.

PURPOSE: We evaluated recurrence outcomes of penile sparing surgery in what is to our knowledge the largest multicenter cohort of patients to date. MATERIALS AND METHODS: We retrospectively identified patients treated with penile sparing surgery from May 1990 to July 2016 at 5 tertiary referral institutions. Treatments consisted of circumcision, wide local excision, laser therapy with or without local excision, partial or total glansectomy and glans resurfacing. The study primary end point was local recurrence-free survival, defined from initial treatment to time of local recurrence and estimated with the Kaplan-Meier method. RESULTS: After applying study exclusion criteria 1,188 patients were included in analysis. During the median followup of 43.0 months there were 252 local recurrences (21.2%), of which 99 (39.3%) developed in year 1. Median time to local recurrence was 16.3 months and the 5-year local recurrence-free survival incidence was 73.6%. When stratified by stage, the 5-year local recurrence-free survival rate was 75.0%, 71.4% and 75.9% in Ta/Tis, T1 and T2 cases, respectively (log rank p = 0.748). Of the recurrences 58.3% were treated with repeat organ sparing procedures and the secondary partial (total) penectomy rate was 19.0%. Only margin status was significantly associated with local recurrence on multivariate analysis (p = 0.001). Study limitations included the retrospective design and the heterogeneous clinical approach. CONCLUSIONS: Penile sparing surgery can provide excellent local control for superficial penile tumors as well as for appropriately selected invasive lesions. Strict followup in the early postoperative period is highly recommended.

Surgical management of penile carcinoma in situ: results from an international collaborative study and review of the literature.

OBJECTIVES: To evaluate recurrence after penile-sparing surgery (PSS) in the management of carcinoma in situ (CIS) of the penis in a large multicentre cohort of patients. PATIENTS AND METHODS: We identified consecutive patients from five major academic centres, treated between June 1986 and November 2014, who underwent PSS for pathologically proven penile CIS. The primary outcome was local recurrence-free survival (RFS), which was estimated using the Kaplan-Meier method. RESULTS: A total of 205 patients were identified. Treatment methods included circumcision, glansectomy, wide local excision, laser therapy and total glans resurfacing. Over a median (interquartile range [IQR]) follow-up of 40 (26-65.6) months, there were 48 local recurrences, with 45.8% occurring in the first year and 81.3% occurring by year 5. The majority of recurrences were observed in the laser group (58.3%). The median (IQR) time to local recurrence was 15.9 (5.66-26.14) months. The 1- 2- and 5-year RFS rates were 88.4, 85.6 and 75%, respectively, and the median (IQR) RFS time was 106.5 (80.2-132.2) months. CONCLUSIONS: Among patients with penile CIS selected for surgical management, durable responses at intermediate- to long-term follow-up were noted. For those with glandular CIS, glans resurfacing offered the best outcomes.

Clinicopathological features of carcinoma of the distal penile urethra.

Distal urethral carcinomas are very rare and are similar in their pathology and behaviour to tumours of the glans penis and foreskin. Similarly they are associated with penile intraepithelial neoplasia (PeIN) of both differentiated and undifferentiated types. Current management is mainly surgical, but increasingly involves specialist penile-preserving techniques. Handling and dissection of the specimens is broadly the same as other primary penile tumours. The prognosis of distal urethral lesions is believed to be worse than penile tumours and better than prostatic urethral tumours, but the evidence is sparse. The staging system for urethral tumours does not distinguish between proximal and distal, apart from prostatic urethra, and has led to much confusion in the literature. Although the subtypes of tumours seen in the distal urethra are the same as those on the glans and foreskin, there is an increased proportion of basaloid squamous carcinoma and malignant melanoma whereas the majority of tumours seen in the proximal and prostatic urethra are of urothelial origin. In future, distal urethral tumours should be separately designated with site-specific staging/TNM and reporting system and pathologically classified in the same way as penile and foreskin tumours. Ultimately, this will improve the quality of data and produce evidence to inform management.

Glans resurfacing for precancerous and superficially invasive carcinomas of the glans penis: Pathological specimen handling and reporting.

Glans resurfacing is a recently described technique in the management of precancerous lesions and superficial invasive tumours of the glans penis as well as cases of indolent persistent lichen sclerosus. The technique is complex and is usually only practiced in specialist centres with combined urological and plastic surgical expertise. Cosmetic and functional results are better than in more extensive penile surgery, such as glansectomy, for such cases, cancer cure and control is comparable. Knowledge of the technique used and the spectrum of disease are vital for appropriate specimen handling and pathological reporting of these complex cases to aid further management and avoid over reporting of positive margins.

Lymphovascular and perineural invasion are risk factors for inguinal lymph node metastases in men with T1G2 penile cancer.

PURPOSE: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. METHODS: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. RESULTS: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6-11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6-9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99-1.04, p = 0.17). CONCLUSION: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

A global approach to improving penile cancer care.

Rare tumours such as penile carcinoma have been largely neglected by the urology scientific community in favour of more common - and, therefore, more easily fundable - diseases. Nevertheless, penile cancer represents a rising burden for health-care systems around the world, because a lack of widespread expertise, ineffective centralization of care and absence of research funds have hampered our ability to improve the global care of these patients. Moreover, a dichotomy has arisen in the field of penile cancer, further impeding care: the countries that are mainly supporting research on this topic through the development of epidemiological studies and design of clinical trials are not the countries that have the highest prevalence of the disease. This situation means that randomized controlled trials in developed countries often do not meet the minimum accrual and are intended to close before reaching their end points, whereas trials are almost completely absent in those areas with the highest disease prevalence and probability of successful recruitment, such as Africa, South America and South Asia. The scientific and organizational inaction that arises owing to this mismatch translates into a burdensome cost for our patients. A global effort to gather experts and pull together scientific data from around the world may be the best way to boost clinical research, to change clinical practice and, ultimately, to improve care for patients and their families.

The retinoblastoma protein/p16 INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma.

AIMS: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell-cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell-cycle proteins: p53, p21, p16(INK4A) and retinoblastoma (RB) protein. METHODS AND RESULTS: One hundred and forty-eight PSCC samples were examined immunohistochemically for RB, p16(INK4A) , p53 and p21 protein expression. One hundred and two cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours, with HPV16 present in 81%. Basaloid tumours were related strongly to HPV infection (10 of 13), while verrucous were not (three of 13). Fifty-nine per cent (38 of 64) of usual type SCCs had HPV infection. RB protein correlated negatively (P<0.0001) and p16(INK4A) (P<0.0001) and p21 (P=0.0002) correlated positively with HPV infection. p53 did not correlate with HPV infection. CONCLUSIONS: HPV infection is present in more than half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual-type PSSCs correlate with HPV infection, confirming possible separate aetiologies for those tumours.

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis.

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16(INK4A) and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16(INK4A) and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16(INK4A) and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16(INK4A) expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.

Penile preserving surgery and surgical strategies to maximize penile form and function in penile cancer: recommendations from the United Kingdom experience.

OBJECTIVES: The diagnosis of penile cancer can be devastating for a man and his partner. The fear of cancer is heightened by the prospect of penile amputation. While conventional radical surgery continues to be an effective approach to management, the emasculating nature of this treatment has serious psychological and sexual morbidity. Recent studies have challenged the traditional belief that a 2 cm margin was required for adequate oncological control. METHODS: We review the current options and status of such penile preserving techniques in the modern day management of penile cancer, and assess the use of the different techniques according to the stage and grade of disease based upon the combined experience of two superregional centres in the United Kingdom. RESULTS: A range of organ preserving procedures matches the clinical spectrum of patients presenting with penile cancer. These demonstrate excellent oncological control whilst maximizing penile function and form. CONCLUSION: Innovative surgical techniques can now preserve as much penile tissue and functional integrity as possible, without compromising oncological control. This minimizes the impact of disease and its treatment on the quality of life of the patient.

Laser ablation as monotherapy for penile squamous cell carcinoma: A multi-center cohort analysis.

INTRODUCTION: Although the trend towards penile sparing therapy is increasing for penile squamous cell carcinoma, outcomes for laser ablation therapy have not been widely reported. We assessed the clinical outcomes of penile cancer patients treated with only laser ablation. MATERIALS AND METHODS: A retrospective review was performed on 161 patients across 5 multi-center tertiary referral centers from 1985 to 2015. All patients underwent penile sparing surgery with only laser ablation for squamous cell carcinoma of the penis. Laser ablation was performed with neodymium-doped yttrium aluminum garnet or carbon dioxide. Overall and recurrence-free survival was calculated using the Kaplan-Meier method and compared with the log rank test. RESULTS: A total of 161 patients underwent laser ablation for penile cancer. The median age was 62 (IQR: 52-71) years and median follow-up was 57.7 (IQR: 28-90) months. The majority of patients were pTa/Tis (59, 37%) or pT1a (62, 39%). Only 19 (12%) had a poorly differentiated grade. The 5-year recurrence-free survival was 46%. When stratified by stage, the 5-year local recurrence-free survival was pTa/Tis: 50%; pT1a: 41%; pT1b: 38%; and pT2: 52%. The inguinal/pelvic nodal recurrence was pTa/Tis: 2%; pT1a: 5%; pT1b: 18%; and pT2: 22%. There were no differences among stages with respect to recurrence-free survival (P = 0.98) or overall survival (P = 0.20). CONCLUSION: Laser ablation therapy is safe for appropriately selected patients with penile squamous cell carcinoma. Due to the increased risk of nodal recurrence, laser ablation coupled with diagnostic nodal staging is indicated for patients with pT1b or higher.

Glansectomy as Primary Management of Penile Squamous Cell Carcinoma: An International Study Collaboration.

OBJECTIVE: To analyze the recurrence and survival outcomes of glansectomy in patients with penile squamous cell carcinoma. MATERIALS AND METHODS: We performed a retrospective review of 410 patients across 5 international tertiary referral centers between 1999 and 2016. All patients had tumors involving the glans penis and underwent glansectomy as primary treatment. The Kaplan-Meier method and log-rank test were used to calculate survival and recurrence. Median follow-up was 42 months (interquartile range [IQR] 29-56). RESULTS: The median age was 64 years (IQR 53-72). Median tumor size was 2.2 cm (IQR 1.5-3.0). A total of 240 patients (58.5%) had pT2 disease, whereas only 43 patients (10.5%) had pT3 or pT4 disease. The majority of the cohort had poorly differentiated tumors (43.7%). Most recurrences were local at 7.6% (31 patients). Only 14 patients (3.4%) had regional recurrence and 9 patients (2.2%) had distant recurrence. When stratified by pathologic stage, tumors that were pT2 or higher were (P < .001) and were more likely to be poorly differentiated (P < .001). There were no differences in recurrence location among pathologic stages (P = .15). The 1-, 2-, and 5-year recurrence-free survival were 98%, 94%, and 78%, respectively. There were no differences in overall survival when stratified by stage (P = .67). CONCLUSION: Glansectomy is an oncologically safe treatment modality for squamous cell carcinoma of the glans in appropriately selected invasive tumors.

Sticks and stones: use of acupuncture in extracorporeal shockwave lithotripsy.

BACKGROUND AND PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is an effective noninvasive, outpatient method of stone clearance. In our unit, it is performed using a combination of oral analgesia and intravenous sedation, which allows us to treat to therapeutic levels in the vast majority of our patients. However, we have encountered patients who do not tolerate various elements of the analgesia protocol and thus cannot be treated to full effect. The options for these people are currently limited to either SWL under formal sedation or epidural or general anesthetic or the use of another technique of stone clearance, such as percutaneous nephrolithotomy, which may not be as appropriate, and again necessitates an anesthetic, an inpatient stay, or both. PATIENTS AND METHODS: We describe three patients who had previously failed SWL who received acupuncture in place of standard analgesia prior to the next treatment. RESULTS: All three patients were able to tolerate the procedure better and were treated at a higher level with more shocks than in the previous session. No side effects were noted. CONCLUSIONS: We propose that acupuncture may be considered in patients unable to take standard sedoanalgesia. It is a cost-effective, safe method of inducing sedation with analgesia and had no demonstrable side effects in our series. It provides an attractive alternative to the use of general or regional anesthetics in these patients.

Treatment of carcinoma in situ of the glans penis with topical chemotherapy agents.

BACKGROUND: The use of topical agents in the treatment of carcinoma in situ (CIS) of the penis has been well described in the literature. Previous studies have been limited by small sample size and imprecise end points. OBJECTIVE: Establish the response rate of 5-fluorouracil (5-FU) and imiquimod (IQ) in the treatment of penile CIS in a large contemporary series in a supranetwork centre. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all primary and recurrent cases of penile CIS treated with 5-FU and IQ identified from a prospective database over a 10-yr period. Therapy was standardised in all cases with application to the lesion for 12h every 48 h for 28 d. INTERVENTION: 5-FU was the first-line therapy, and IQ was the second-line topical agent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was defined as complete response (CR; i.e., resolution of lesion), partial response (PR; i.e., lesion reduced in size and or visibility), or no response (NR; ie, no improvement in lesion size and or visibility). The secondary end points included local toxicity and adverse events. No statistical analysis or software was used. RESULTS AND LIMITATIONS: A total of 86 patients were diagnosed with CIS of the penis over the 10-yr period. Forty-four (51%) received topical chemotherapy. The mean follow-up was 34 mo. CR to topical chemotherapy was seen in 25 (57%), PR was seen in 6 (13.6%), and NR was seen in the remaining 13 (29.5%) patients. Local toxicity was experienced by 10% of patients, and 12% had an adverse event following application of 5-FU. The retrospective design and short follow-up were the major limitations of this study. CONCLUSIONS: Topical chemotherapy agents are moderately effective first-line therapy in the treatment of penile CIS. Toxicity and adverse events were few with our treatment protocol. The issues of long-term surveillance and assessment of partial responders remain a challenge. Topical chemotherapy should remain a first-line treatment option for penile CIS.

Alternative HER/PTEN/Akt pathway activation in HPV positive and negative penile carcinomas.

BACKGROUND: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its impact on Akt activation using immunohistochemistry and fluorescent in situ hybridisation (FISH). METHODOLOGY/PRINCIPAL FINDINGS: 148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were also evaluated using FISH. HPV presence was assessed by PCR. pEGFR expression was detected significantly less frequently in HPV-positive than HPV-negative tumours (p = 0.0143). Conversely, HER3 expression was significantly more common in HPV-positive cases (p = 0.0128). HER4, pAkt, Akt and PTEN protein expression were not related to HPV. HER3 (p = 0.0054) and HER4 (p = 0.0002) receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with tumour grade (HER3, p = 0.0029; HER4, p = 0.0118; Akt1, p = 0.0001). pEGFR expression correlated with pAkt but not with tumour grade or stage. There was no EGFR gene amplification. HER2 was not detected. PTEN protein expression was reduced or absent in 62% of tumours but PTEN gene copy loss was present only in 4% of PSCCs. CONCLUSIONS/SIGNIFICANCE: EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis. HPV-negative tumours tend to express significantly more pEGFR than HPV-positive cancers and this expression correlates with pAkt protein, indicating EGFR as an upstream regulator of Akt signalling in PSCC. Conversely, HER3 expression is significantly more common in HPV-positive cases and positively correlates with cytoplasmic Akt1 expression. HER4 and PTEN protein expression are not related to HPV infection. Our results suggest that PSCC patients could benefit from therapies developed to target HER receptors.

EAU penile cancer guidelines 2009.

CONTEXT: Squamous cell carcinoma (SCC) of the penis is a relatively rare but ominous disease. OBJECTIVE: To present a condensed version of the updated 2009 European Association of Urology (EAU) guidelines on penile SCC. EVIDENCE ACQUISITION: We performed a literature search of new data available up to December 2009. No randomized study was found; consequently, level of evidence (LE) and grade of recommendations (GR) are low. EVIDENCE SYNTHESIS: More insight was gained into the etiology of SCC of the penis, together with improved staging and treatment: Human papillomavirus 16 plays an etiologic role in approximately 40-50% of cases. Similarities in etiology with SCC of the head and neck, the female genitalia, and the anal canal have been found. Improved diagnostics allowed earlier diagnosis, leading to more conservative treatments. Adjuvant and neoadjuvant chemotherapy showed promising results in patients with advanced or recurrent disease. Centralization of the disease contributed to standardization and rapid diffusion of new treatments with improved results and increased organ preservation. CONCLUSIONS: Improvements in the management of SCC of the penis are reflected in changes in the guidelines, but the rarity of the disease precluded randomized studies, leading to low level of evidence and grade of recommendation.

Evaluation of dynamic lymphoscintigraphy and sentinel lymph-node biopsy for detecting occult metastases in patients with penile squamous cell carcinoma.

OBJECTIVE: To evaluate the introduction of dynamic lymphoscintigraphy and sentinel lymph-node (SLN) biopsy (used to detect occult lymph node metastases in patients with penile cancer and clinically impalpable inguinal lymph nodes at presentation) at a UK tertiary referral centre for penile cancer. PATIENTS AND METHODS: In all, 75 patients with penile squamous cell carcinoma of stage T1, grade > or = 2, and unilateral or bilateral impalpable groin nodes, were prospectively enrolled over a 2-year period. Patients underwent lymphoscintigraphy with (99m)technetium-labelled nanocolloid which was injected intradermally around the tumour or into the distal penile shaft skin. Four hours later, the SLN(s) were identified during surgery using a hand-held gamma-probe and intradermal injections with blue dye. Completion lymph node dissection was subsequently used in patients with tumour-positive SLNs. RESULTS: In all, 255 SLNs were removed from 143 groins; all excised nodes had taken up the radioactive marker, and the blue dye was evident in 87%. Eighteen of 75 (24%) patients and 21 of 143 groins (15%) had a tumour-positive SLN. All but one patient went on to completion lymph node dissection. Three of these 18 (17%) had further disease in other than SLNs. Six of 143 (4%) groins developed minor complications. One false-negative result was reported at a median (range) follow-up of 11 (2-24) months. CONCLUSION: This technique is feasible for managing penile cancer in a UK tertiary referral centre. The initial results suggest that it can accurately identify the SLN(s), which can then be removed for pathological review with minimal morbidity.

Reconstructive surgery for invasive squamous carcinoma of the glans penis.

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.

Penile-preserving surgery for male distal urethral carcinoma.

OBJECTIVE: To evaluate medium-term outcome data from patients with distal urethral cancers treated with penile-preserving surgery. PATIENTS AND METHODS: We analysed prospectively 18 consecutive men referred for the management of urethral carcinoma. All had a specialist review in a supra-regional multidisciplinary team meeting, where the histology findings were reviewed by one pathology consultant. Tumours were staged according to the Tumour-Node-Metastasis classification and the patients offered penile-preserving surgery when tumours were limited to the glanular or penile urethra. RESULTS: All 18 patients were suitable for penile-preserving surgery; the procedures were: three hypospadias formation with or without topical chemotherapy; four buccal mucosa urethroplasty; three glansectomy and reconstruction; six glansectomy, distal corporectomy, reconstruction and hypospadias formation; two urethrectomy with or with no excision of adjacent tunica albuginea. The mean (median, range) follow-up was 26 (20.5, 9-58) months. There were no local recurrences; four patients with regional nodal disease progressed and of these, two died from metastatic disease, and one died from an unrelated condition. CONCLUSION: Medium-term data show that penile-preserving surgery is a feasible treatment for men with distal urethral carcinoma, providing excellent local control without prejudicing survival; a longer follow-up is needed.

Total glans resurfacing for premalignant lesions of the penis: initial outcome data.

OBJECTIVE: To report our initial experience of total glans resurfacing (TGR), as premalignant lesions of the glans penis have conventionally been treated by local excision, topical chemotherapy, laser or cryotherapy, but these techniques are frequently associated with high local failure rates and unsightly scarring that can make monitoring by gross inspection difficult. PATIENTS AND METHODS: TGR involves removing the glans and subcoronal epithelial and subepithelial tissues down to the corpus spongiosum of the glans and Buck's fascia at the coronal sulcus. The denuded glans penis is then covered with an extra-genital skin graft. Ten patients underwent TGR: six had recurrent erythroplasia of Queyrat after 5% 5-fluorouracil (5-FU) therapy; one had no clinical response to 5-FU or imiquimod; one had a severe allergic reaction and therefore could not tolerate 5-FU; and two had extensive glans hyperkeratosis and severe dysplasia. RESULTS: There were no postoperative complications. All skin grafts took successfully, and the cosmetic results were excellent. In all cases, pathological resection margins were clear. To date, there has been no evidence of disease recurrence on follow-up (median 30 months, range 7-45). CONCLUSIONS: TGR is a successful surgical alternative for managing intractable premalignant penile lesions. It has the potential to restore normal anatomy and minimize the risk of local recurrence by replacing diseased epithelium and subepithelial tissues with healthy extra-genital skin.