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PREDICTORS OF PENILE CANCER RECURRENCE FOLLOWING CONSERVATIVE SURGICAL RESECTION
202
THE JOURNAL OF UROLOGY®
N0 groin and positive PET scan will benefit from immediate groin node dissection where as with negative PET scan can be observed safely. A significant limitation of PET is its false positive findings in case of infective nodes. However, further studies are required to confirm these findings. Source of Funding: None
566 PREDICTORS OF PENILE CANCER RECURRENCE FOLLOWING CONSERVATIVE SURGICAL RESECTION. Gareth M Brown*, Abbas Khadra, Amr Abdelraheem, Giulio Garaffa, Alex Freeman, Rowland W Rees, Asif Muneer, David J Ralph, Suks Minhas, London, United Kingdom INTRODUCTION AND OBJECTIVE: A number of surgical techniques are used in penile preserving surgery in the management of penile carcinoma. However, improved functional and psychological outcomes of these techniques must be counterbalanced by the rate of loco-regional and metastatic tumour recurrence. The aim of this study was to assess the long term outcome of conservative surgery for penile cancer and identify parameters which can predict tumour recurrence. METHODS: Patients undergoing surgery for penile cancer in a single unit were identified and long term outcomes were recorded. The original histopathological characteristics were recorded including primary tumour type, grade and stage; the presence of lymphovascular invasion; the association of BXO and CIS; and the occurrence of metastases and site of any tumour recurrence. A Chi squared test was used for statistical analysis. RESULTS: Between January 2002 and May 2008, 174 men were followed up after conservative surgical treatment of their penile cancer. Conservative treatment included partial penectomy with reconstruction, glansectomy and glans resurfacing. 132 (75.6%) remained tumour free with 23 men (13%) developing local recurrence at the site of primary resection and 19 (11%) patients developing metastases within the groin basins or at distant sites. The stage of the initial tumour, the presence of lymphovascular invasion, and the presence of pathological lymph nodes were independent predictors of tumour recurrence (p<0.01). There were no significant prognostic factors differentiating between local tumour recurrence and metastases. As expected tumour recurrence was ultimately associated with a higher incidence of death. Mortality rates were 30.9% for overall tumour recurrence (21.7% local recurrence and 42.1% metastases), compared with 9.1 % in those men recurrence free. CONCLUSIONS: Conservative surgical treatment of penile cancer is best suited to those men who at the time of initial surgery have a lower tumour stage (pT<2), no lymphovascular invasion, and no pathological lymph nodes. Each of these factors is independently associated with a greater incidence of tumour recurrence and subsequent higher patient mortality. Therefore, the surgical management of men with these characteristics should be approached with a lower threshold towards more radical surgical treatment or offered adjuvant treatment modalities. Source of Funding: None
567 METASTASIS SUPPRESSOR GENE NM23-H1 IS A PROGNOSTIC PARAMETER FOR THE OCCURRENCE OF LYMPH NODE METASTASES IN PENILE CARCINOMAS. Chris Protzel*, Rostock, Germany; Christoph Kakies, Greifswald, Germany; Micaela Poetsch, Essen, Germany; Juergen Giebel, Greifswald, Germany; E. Wolf, Hamburg, Germany; Oliver W. Hakenberg, Rostock, Germany INTRODUCTION AND OBJECTIVE: Previous studies have shown the prognostic value of nm23-H1 for lymph node metastasis and survival in several tumor entities. Since survival in penile squamous cell carcinomas (PSCC) highly depends on early detection and resection of lymphnode metastasis, nm23-H1 examination in primary tumors could help to improve the management of patients with penile carcinoma.
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
METHODS: Expression of nm23-H1 was immunohistochemically examined with an anti-nm23-H1 monoclonal antibody in 30 invasive primary penile squamous cell carcinomas. Expression of nm23-H1 was classified according to the degree of nm23-H1 positive tumor cells as positive, decreased or negative. The presence of HPV 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Immunohistochemical data were compared to clinical data. RESULTS: 12 (40%) tumors showed positive nm23-H1 expression, 16 (53.3%) a decreased and 2 (6.7%) no expression. Lymph node metastases were detected in 16 out of 18 patients with decreased or negative nm23-H1 expression in the primary tumor (p<0.0001). Patients with positive nm23-H1 expression had a significantly better prognosis for survival compared to the other groups (p<0.003). Multivariate analysis demonstrated a significant prognostic value of nm23-H1 for lymph node metastasis (p<0.05). There was no significant association between nm23-H1 expression and presence of HPV DNA. CONCLUSIONS: Decreased or missing expression of nm23-H1 metastasis suppressor gene significantly correlates with the occurrence of lymph node metastases in PSCC. Our data suggest nm23-H1 expression to be an important prognostic parameter for tumor progression, development of metastasis and disease specific death. Source of Funding: None
568 EXPRESSION OF ANNEXINS I, II AND IV IN HUMAN PENILE SQUAMOUS CELL CARCINOMAS. Chris Protzel*, Rostock, Germany; Matthias Richter, Uwe Zimmermann, Juergen Giebel, Greifswald, Germany; Oliver W. Hakenberg, Rostock, Germany INTRODUCTION AND OBJECTIVE: Since the outcome of patients with penile squamous cell carcinomas (PSCC) largely depends on occurrence of metastasis prognostic markers indicating the risk for tumor cell spreading would be useful. Annexins representing a family of calcium and phospholipid binding proteins are potential prognostic markers in a variety of tumors. Therefore we immunohistochemically examined the expression of Annexins I, II and IV (ANX AI, ANX AII and ANX AIV) in PSCC. METHODS: Samples originated from 29 patients subjected to surgical resection of invasive PSCC. Immunohistochemistry was done on paraffin-embedded sections using monoclonal antibodies against ANX AI, ANX AII and ANX AIV. Expression of ANXs was compared with clinical data. RESULTS: ANX AI expression was found in the cytoplasm and nucleus of tumor cells in conventional PSCC and was absent in basaloid and sarcomatoid subtypes. High ANX AI score was significantly associated with higher T stages (p=0.006). Strong expression in the invasion front of carcinomas was significantly associated with the occurrence of lymph node metastases (p=0.001). ANX AII was mostly localized to tumor cell membranes and showed no association with clinical data. ANX AIV expression was weak in conventional PSCC while it was strong in basaloid and sarcomatoid subtypes. Strong expression of Annnexin IV in the invasion front also showed a significant association with metastases (p=0.019). CONCLUSIONS: In summary, expression of ANXs was different in histological subtypes of penile carcinomas. Strong expression of ANX AI and ANX AIV in the invasion front seems to indicate a higher risk of lymph node metastases. Source of Funding: None
THE JOURNAL OF UROLOGY®
N0 groin and positive PET scan will benefit from immediate groin node dissection where as with negative PET scan can be observed safely. A significant limitation of PET is its false positive findings in case of infective nodes. However, further studies are required to confirm these findings. Source of Funding: None
566 PREDICTORS OF PENILE CANCER RECURRENCE FOLLOWING CONSERVATIVE SURGICAL RESECTION. Gareth M Brown*, Abbas Khadra, Amr Abdelraheem, Giulio Garaffa, Alex Freeman, Rowland W Rees, Asif Muneer, David J Ralph, Suks Minhas, London, United Kingdom INTRODUCTION AND OBJECTIVE: A number of surgical techniques are used in penile preserving surgery in the management of penile carcinoma. However, improved functional and psychological outcomes of these techniques must be counterbalanced by the rate of loco-regional and metastatic tumour recurrence. The aim of this study was to assess the long term outcome of conservative surgery for penile cancer and identify parameters which can predict tumour recurrence. METHODS: Patients undergoing surgery for penile cancer in a single unit were identified and long term outcomes were recorded. The original histopathological characteristics were recorded including primary tumour type, grade and stage; the presence of lymphovascular invasion; the association of BXO and CIS; and the occurrence of metastases and site of any tumour recurrence. A Chi squared test was used for statistical analysis. RESULTS: Between January 2002 and May 2008, 174 men were followed up after conservative surgical treatment of their penile cancer. Conservative treatment included partial penectomy with reconstruction, glansectomy and glans resurfacing. 132 (75.6%) remained tumour free with 23 men (13%) developing local recurrence at the site of primary resection and 19 (11%) patients developing metastases within the groin basins or at distant sites. The stage of the initial tumour, the presence of lymphovascular invasion, and the presence of pathological lymph nodes were independent predictors of tumour recurrence (p<0.01). There were no significant prognostic factors differentiating between local tumour recurrence and metastases. As expected tumour recurrence was ultimately associated with a higher incidence of death. Mortality rates were 30.9% for overall tumour recurrence (21.7% local recurrence and 42.1% metastases), compared with 9.1 % in those men recurrence free. CONCLUSIONS: Conservative surgical treatment of penile cancer is best suited to those men who at the time of initial surgery have a lower tumour stage (pT<2), no lymphovascular invasion, and no pathological lymph nodes. Each of these factors is independently associated with a greater incidence of tumour recurrence and subsequent higher patient mortality. Therefore, the surgical management of men with these characteristics should be approached with a lower threshold towards more radical surgical treatment or offered adjuvant treatment modalities. Source of Funding: None
567 METASTASIS SUPPRESSOR GENE NM23-H1 IS A PROGNOSTIC PARAMETER FOR THE OCCURRENCE OF LYMPH NODE METASTASES IN PENILE CARCINOMAS. Chris Protzel*, Rostock, Germany; Christoph Kakies, Greifswald, Germany; Micaela Poetsch, Essen, Germany; Juergen Giebel, Greifswald, Germany; E. Wolf, Hamburg, Germany; Oliver W. Hakenberg, Rostock, Germany INTRODUCTION AND OBJECTIVE: Previous studies have shown the prognostic value of nm23-H1 for lymph node metastasis and survival in several tumor entities. Since survival in penile squamous cell carcinomas (PSCC) highly depends on early detection and resection of lymphnode metastasis, nm23-H1 examination in primary tumors could help to improve the management of patients with penile carcinoma.
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
METHODS: Expression of nm23-H1 was immunohistochemically examined with an anti-nm23-H1 monoclonal antibody in 30 invasive primary penile squamous cell carcinomas. Expression of nm23-H1 was classified according to the degree of nm23-H1 positive tumor cells as positive, decreased or negative. The presence of HPV 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Immunohistochemical data were compared to clinical data. RESULTS: 12 (40%) tumors showed positive nm23-H1 expression, 16 (53.3%) a decreased and 2 (6.7%) no expression. Lymph node metastases were detected in 16 out of 18 patients with decreased or negative nm23-H1 expression in the primary tumor (p<0.0001). Patients with positive nm23-H1 expression had a significantly better prognosis for survival compared to the other groups (p<0.003). Multivariate analysis demonstrated a significant prognostic value of nm23-H1 for lymph node metastasis (p<0.05). There was no significant association between nm23-H1 expression and presence of HPV DNA. CONCLUSIONS: Decreased or missing expression of nm23-H1 metastasis suppressor gene significantly correlates with the occurrence of lymph node metastases in PSCC. Our data suggest nm23-H1 expression to be an important prognostic parameter for tumor progression, development of metastasis and disease specific death. Source of Funding: None
568 EXPRESSION OF ANNEXINS I, II AND IV IN HUMAN PENILE SQUAMOUS CELL CARCINOMAS. Chris Protzel*, Rostock, Germany; Matthias Richter, Uwe Zimmermann, Juergen Giebel, Greifswald, Germany; Oliver W. Hakenberg, Rostock, Germany INTRODUCTION AND OBJECTIVE: Since the outcome of patients with penile squamous cell carcinomas (PSCC) largely depends on occurrence of metastasis prognostic markers indicating the risk for tumor cell spreading would be useful. Annexins representing a family of calcium and phospholipid binding proteins are potential prognostic markers in a variety of tumors. Therefore we immunohistochemically examined the expression of Annexins I, II and IV (ANX AI, ANX AII and ANX AIV) in PSCC. METHODS: Samples originated from 29 patients subjected to surgical resection of invasive PSCC. Immunohistochemistry was done on paraffin-embedded sections using monoclonal antibodies against ANX AI, ANX AII and ANX AIV. Expression of ANXs was compared with clinical data. RESULTS: ANX AI expression was found in the cytoplasm and nucleus of tumor cells in conventional PSCC and was absent in basaloid and sarcomatoid subtypes. High ANX AI score was significantly associated with higher T stages (p=0.006). Strong expression in the invasion front of carcinomas was significantly associated with the occurrence of lymph node metastases (p=0.001). ANX AII was mostly localized to tumor cell membranes and showed no association with clinical data. ANX AIV expression was weak in conventional PSCC while it was strong in basaloid and sarcomatoid subtypes. Strong expression of Annnexin IV in the invasion front also showed a significant association with metastases (p=0.019). CONCLUSIONS: In summary, expression of ANXs was different in histological subtypes of penile carcinomas. Strong expression of ANX AI and ANX AIV in the invasion front seems to indicate a higher risk of lymph node metastases. Source of Funding: None