Dynamic sentinel node biopsy in penile cancer: initial experiences at a Swedish referral centre.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? According to the current European Association of Urology Guidelines, dynamic sentinel node biopsy is the recommended approach to assess lymph node status in men with cN0 intermediate and high risk penile cancer. Nevertheless, most encouraging results derive from a limited number of studies. The present study shows a false-negative rate of 15%, comparable with or better than several previous studies. Nevertheless, the aim should be a false-negative rate of no more than 5%. We conclude that increased overall experience and the use of the complete modern dynamic sentinel node biopsy protocol are paramount to improve results. OBJECTIVE: • To evaluate the false-negative rate and complication rate of dynamic sentinel node biopsy (DSNB) in penile cancer. PATIENTS AND METHODS: • In this retrospective study, 58 unilaterally or bilaterally clinically lymph node negative (cN0) patients with penile cancer (57 squamous cell carcinomas and one malignant melanoma), scheduled for DSNB at the Örebro University Hospital, Sweden, between 1999 and 2011, were analysed. • Preoperative ultrasonography and fine-needle aspiration cytology of suspicious nodes were not introduced until 2008. • Patients were assessed by lymphoscintigraphy using (99m) technetium nanocolloid on the day before surgery and the dissection of sentinel nodes was aided by the lymphoscintigraphic images and intraoperative detection of radiotracer and patent blue dye. • The false-negative rate and complication rate were calculated per groin. RESULTS: • Of the 58 patients, 32 (55%) underwent preoperative ultrasonography. • Two patients had positive fine-needle aspiration cytology and discontinued further DSNB protocol. Of the remaining 56 patients, all but one were bilaterally cN0 and hence 111 cN0 groins were assessed by lymphoscintigraphy. • In the 55 bilaterally cN0 patients, lymphoscintigraphy visualized a bilateral sentinel node in 34 (62%). • At surgery, all excised sentinel nodes were radioactive while 43% were additionally blue. In total, at least one sentinel node was harvested in 96 (86%) of the DSNB staged groins. • A positive sentinel node was found in 11 groins (bilaterally in three patients). During a median follow-up of 21 months, two false-negative cases emerged, producing a false-negative rate of 15%. Both false-negative cases occurred during the first half of the study. The complication rate was 10%. The majority of complications were minor and transient. CONCLUSIONS: • DSNB is a minimally invasive staging tool in men with cN0 penile cancer, enabling early detection of metastatic disease and thus optimal care. • Our false-negative rate of 15% is comparable or even favourable in comparison with several previous studies, but far from the 5% or less that we aim for. The complication rate found is somewhat higher than previously reported. • With increased overall experience and the continued use of the complete DSNB protocol, we believe our results will improve and the complication rate will decrease.

Initial symptoms and delay in patients with penile carcinoma.

OBJECTIVE: This study aimed to assess initial symptoms and factors associated with patients' and doctors' delay in penile carcinoma. MATERIAL AND METHODS: Fifty consecutive patients with penile carcinoma treated with an organ-sparing technique and nine with partial amputation were enrolled in a prospective study at the Department of Urology, Örebro University Hospital, between 2005 and 2009. Face-to-face structured interviews in combination with self-assessment forms were used for the patients' descriptions of clinical symptoms, treatment seeking and reasons for delay. Data were also extracted from the medical records confirming time-lag between GP assessment, specialist care and time for diagnosis. RESULTS: Erythema, rash and eczema were the most common initial symptoms (35%). In total, 65% had a patients' delay of more than 6 months, and among these there was a small, but not statistically significant, predominance for pT1 and pTis tumours. Living with a stable partner did not affect the delay. The most common reason for patients' delay was the feeling of embarrassment over symptoms localized in a sexual body area. Nine patients had a doctors' delay of more than 3 months from first special visit to diagnosis. Eight of these patients consulted dermatologists and were subjected to repeated biopsies, leaving premalignant results. CONCLUSIONS: A considerable proportion of the patients had a patients' delay of more than 6 months, perhaps due to benign initial symptoms as erythema, rash or eczema. Psychological factors such as embarrassment and denial may also be involved, as well as insufficient awareness or knowledge.

Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma.

OBJECTIVE: • To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters. PATIENTS AND METHODS: • In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Örebro University Hospital, Örebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. • The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. • A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59). RESULTS: • We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. • No significant association between HPV status and pathological tumour stage, grade or lymph node status was found. CONCLUSION: • The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma.

PIK3CA, HRAS and KRAS gene mutations in human penile cancer.

PURPOSE: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways. MATERIALS AND METHODS: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors. RESULTS: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma. CONCLUSIONS: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

Treatment-seeking, aspects of sexual activity and life satisfaction in men with laser-treated penile carcinoma.

OBJECTIVES: The aims were to assess the initial symptoms of penile carcinoma and patients' time frame in treatment seeking, and to describe the effect of laser treatment on sexual activity and life satisfaction. PATIENTS AND METHODS: A retrospective face-to-face structured interview study of patients laser treated for localised penile carcinoma at the department of Urology in Orebro, Sweden, during 1986 to 2000. Sixty-seven was treated and 58 of them (mean age, 63 yr; range, 34-90) were alive at the time of this study. Forty-six (79%) agreed to participate. RESULTS: Ninety-six percent of the patients recalled their first symptom of penile carcinoma. Superficial ulceration and fissures were the most common symptoms (39%). Thirty-seven percent delayed seeking treatment for more than 6 mo. The patients had a greater lifetime number of sexual partners and a greater lifetime prevalence of STIs than a Swedish representative comparator population. Some aspects of sexual life, such as manual stimulation/caressing and fellatio, decreased markedly after laser treatment. Patient satisfaction with life as a whole was approximately the same as that of the general population. CONCLUSIONS: Patients delayed seeking treatment for a considerable period, despite awareness of the first local symptoms. Men with laser-treated localised penile carcinoma resume their sexual activities to a large extent after the treatment. Except for satisfaction with somatic health, similar-or even higher-proportions of patients than comparators are satisfied with life as a whole and with other domains of life including satisfaction with sexual life.

Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients.

BACKGROUND: Current follow-up recommendations for patients with penile carcinoma are based on small numbers of patients. OBJECTIVES: To give further insight into the recurrence patterns of penile carcinoma in different treatment settings and provide recommendations for follow up. DESIGNS, SETTING, AND PARTICIPANTS: In this retrospective study, we analysed 700 patients from two referral centres for penile carcinoma for recurrences. MEASUREMENTS: Recurrences were categorized as local, regional, or distant. The rate of local recurrences was compared between patients undergoing penile-preserving treatments and partial/total amputation. Regional recurrences were compared between patients surgically staged as pN0 or pN+ and clinically node-negative (cN0) patients subjected to a wait-and-see policy. The total recurrence rate, type of recurrence, time to recurrence, and survival were calculated. RESULTS AND LIMITATIONS: 205 out of 700 patients (29.3%) had a recurrence, consisting of 18.6% local, 9.3% regional, and 1.4% distant recurrences. Of the recurrences, 92.2% occurred within 5 yr after primary treatment. All regional and distant recurrences occurred within 50 and 16 mo, respectively. The local recurrence rate was 27.7% after penile-preserving therapy and 5.3% after amputation. The regional recurrence rate was 2.3% in patients staged as pN0, 19.1% in patients staged as pN+, and 9.1% in patients undergoing a wait-and-see policy. The 5-yr disease-specific survival was 92% after a local recurrence and 32.7% after a regional recurrence. All patients with a distant recurrence died within 22 mo. Although the number of analysed patients is substantial, the results do not necessarily reflect those of other centres using different techniques for the management of penile carcinoma. CONCLUSIONS: Patients undergoing penile-preserving therapy, patients surgically staged as pN+, and those undergoing a wait-and-see policy for the nodal status are at high risk of developing a recurrence. Follow-up recommendations are provided based on the risk and impact on survival of a recurrence.

The National Penile Cancer Register in Sweden 2000-2003.

OBJECTIVE: This article reviews the first 4 years of operation of the National Penile Cancer Register (NPECR) in Sweden. The register was set up to gain knowledge about the incidence and primary treatment of penile cancer, including the use of and the frequency of lymph node dissection. The register elicits treatment disparities between regions, and aims to determine the impact of clinical practice guidelines introduced in Sweden. MATERIAL AND METHODS: All patients newly diagnosed with penile cancer after the year 2000 have been registered in the NPECR. A total of 454 patients were registered in the period 2000-2003. RESULTS: Registrations in the NPECR were almost complete, with 98.7% of cases registered in the National Cancer Register also being registered in the NPECR. At least 145 clinicians reported to the register. The annual incidence of penile cancer is 2.2/100 000 men. Squamous cell carcinoma accounts for 95% of the cases. The mean age at diagnosis was 65.5 years. Most tumours were classified as Tis, T1 or T2, each class representing 25-30% of the total number of diagnosed cases. Penis-preserving treatment was performed in 58% of the patients (Table I). The number of patients classified as > or = T1/G2-G3 was 206, and 101 of these patients (49%) underwent inguinal lymphadenectomy. CONCLUSIONS: We have introduced a population-based register in Sweden with almost complete registration, and this offers unique possibilities for further studies of both epidemiological and clinical aspects of penile cancer. The results obtained to date indicate that the primary treatment is done in many settings and that guidelines, e.g. to dissect lymph nodes, are not always followed.

Combined laser treatment for penile carcinoma: results after long-term followup.

PURPOSE: We evaluated local disease control, side effects and cause specific survival of penile carcinoma treated with laser therapy. MATERIALS AND METHODS: In a prospective study from 1986 to 2002 we included 67 men with a mean age of 60 years with newly diagnosed penile carcinoma. No patient was lost to followup. RESULTS: At a median followup of 42 months (range 12 to 186) 59 patients were alive and 8 had died of penile carcinoma (2) and concurrent disease (6). Of the 13 patients (19%) with local recurrence during the study period 10 underwent repeat laser treatment successfully. Side effects were few but 5 patients (7%) had postoperative bleeding. Overall cosmetic and functional results were highly satisfactory. CONCLUSIONS: The results of this study show that treating penile carcinoma with the combination of carbon dioxide and neodymium:YAG lasers can safely be done with highly satisfactory cosmetic results as well as good local tumor control.