37% for pN3.9 In our study, we report broadly similar 5-year CSS with pN1 (72%), pN2 (61%), and pN3 (33%). There are limitations in view of the retrospective nature of the study. Owing to the large size of the catchment area, after primary treatment, patients often moved to their local urology units after a few years making reporting for all patients referred in that period difficult. To circumscribe this, we reported on all patients, where full records could be obtained and who had a minimum of 3 years follow-up to get longterm data. In addition, through the study period, there has been a change in the TNM reporting of penile cancers, and to allow for this, we reclassified tumors according to the 2009 TNM. Another issue is that we did not offer DSLNB at our unit during the study period and relied on a risk-based approach to decide on inguinal LND for nonpalpable nodes at presentation. DSLNB has been shown to be effective and have a low false-negative rate of around 5% in large centers with accumulated experience. It has matured into a reliable and safe method for assessing status of lymph nodes in penile carcinoma patients and has reduced treatment morbidity by improving patient selection for inguinal LND.6,25,26 In our cohort, there is a proportionately larger fraction of patients undergoing modified LND using the risk-based approach; this could be reduced by introducing DSLNB. Although the data represent a single institution, it describes contemporary outcomes in a supraregional UK center as regard to patterns of therapy, oncologic outcomes, and longterm survival. We conclude that supraregional penile cancer management has led to considerable clinical experience in our center over the past decade. Nearly half of all tumors are managed by organ-preserving techniques, but local recurrence rates are higher although most of the recurrences could be managed without amputative surgery. Close follow-up is therefore vital to pick up local recurrence or progression. Overall oncologic outcomes are good with a 5-year CSS of 85%. References 1. Hardner GJ, Bhanalaph T, Murphy GP, et al. Carcinoma of the penis: analysis of therapy in 100 consecutive cases. J Urol. 1972;108: 428. 2. Narayana AS, Olney LE, Loening SA, et al. Carcinoma of the penis: analysis of 219 cases. Cancer. 1982;49:2185. 3. Agrawal A, Pai D, Ananthakrishnan N, et al. The histological extent of the local spread of carcinoma of the penis and its therapeutic implications. BJU Int. 2000;85:299. 4. 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;96:1040. 5. Hegarty PK, Shabbir M, Hughes B, et al. Penile preserving surgery and surgical strategies to maximize penile form and function in penile cancer: recommendations from the United Kingdom experience. World J Urol. 2009;27:179.
UROLOGY 85 (5), 2015
6. Leijte JA, Kroon BK, Valdes Olmos RA, et al. Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma. Eur Urol. 2007;52:170. 7. Pandey D, Mahajan V, Kannan R. Prognostic factors in node-positive carcinoma of the penis. J Surg Oncol. 2006;93:133. 8. Ravi R. Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol. 1993;72:817. 9. Djajadiningrat RS, Graafland NM, van Werkhoven E, et al. Contemporary management of regional nodes in penile cancerimprovement of survival? J Urol. 2014;191:68. 10. Guimaraes GC, Cunha IW, Soares FA, et al. Penile squamous cell carcinoma clinicopathological features, nodal metastasis and outcome in 333 cases. J Urol. 2009;182:528. 11. Moses KA, Winer A, Sfakianos JP, et al. Contemporary management of penile cancer: greater than 15 year MSKCC experience. Can J Urol. 2014;21:7201. 12. National Institute for Health and Clinical Excellence. Improving Outcomes of Urological Cancers. UK. London: NICE; 2003: 83-86. 13. Veeratterapillay R, Sahadevan K, Aluru P, et al. Organ-preserving surgery for penile cancer: description of techniques and surgical outcomes. BJU Int. 2012;110:1792. 14. Coblentz TR, Theodorescu D. Morbidity of modified prophylactic inguinal lymphadenectomy for squamous cell carcinoma of the penis. J Urol. 2002;168:1386. 15. Jacobellis U. Modified radical inguinal lymphadenectomy for carcinoma of the penis: technique and results. J Urol. 2003;169:1349. 16. Pizzocaro G, Algaba F, Horenblas S, et al. EAU penile cancer guidelines 2009. Eur Urol. 2010;57:1002. 17. Ritchie AW, Foster PW, Fowler S, et al. Penile cancer in the UK: clinical presentation and outcome in 1998/99. BJU Int. 2004;94: 1248. 18. Kumar P, Singh S, Goddard JC, et al. The development of a supraregional network for the management of penile cancer. Ann R Coll Surg Engl. 2012;94:204. 19. Arya M, Li R, Pegler K, et al. Long-term trends in incidence, survival and mortality of primary penile cancer in England. Cancer Causes Control. 2013;24:2169. 20. Djajadiningrat RS, van Werkhoven E, Meinhardt W, et al. Penile sparing surgery for penile cancer—does it affect survival? J Urol. 2013. http://dx.doi.org/10.1016/j.juro.2013.12.038; [Epub ahead of print]. 21. Hegarty PK, Eardley I, Heidenreich A, et al. Penile cancer: organsparing techniques. BJU Int. 2013. http://dx.doi.org/10.1111/bju. 12338; [Epub ahead of print]. 22. Leijte JA, Kirrander P, Antonini N, et al. Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients. Eur Urol. 2008;54:161. 23. Lont AP, Kroon BK, Gallee MP, et al. Pelvic lymph node dissection for penile carcinoma: extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol. 2007;177:947. 24. Svatek RS, Munsell M, Kincaid JM, et al. Association between lymph node density and disease specific survival in patients with penile cancer. J Urol. 2009;182:2721. 25. Kroon BK, Horenblas S, Estourgie SH, et al. How to avoid falsenegative dynamic sentinel node procedures in penile carcinoma. J Urol. 2004;171:2191. 26. Tanis PJ, Lont AP, Meinhardt W, et al. Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique. J Urol. 2002;168:76.
EDITORIAL COMMENT Supraregional multidisciplinary teams (MDT) have managed penile cancer in the United Kingdom since the publication of
1101
the National Institute for Clinical Excellence Penile Cancer Guidelines in 2002.1 Such teams serve a catchment area of about 4 million patients and see a minimum of 25 patients per year. Given the rarity of the disease in the United Kingdom and other developed nations, such an approach fosters the delivery of guideline-based approaches to penile cancer management for all patients, multidisciplinary cancer management, clinical research, and the relatively rapid development of expertise among participating physicians in part by increasing patient volume.2-6 In the present study,7 from one such MDT, at Sunderland Royal Hospital, the presenting clinical features, treatment, and outcomes over an 11-year period were retrospectively reviewed. The series consisted of 203 patients with a median follow-up of 5 years. Of note is that the reported cohort is somewhat smaller than the total number seem during that time period due to the lack of complete data on all patients. However, the reported number still represents an average of about 18 seen patients per year. This is significantly more than the 1-2 patients seen per year by the average consultant before institution of the National Institute for Clinical Excellence guidelines.8 The authors managed the primary tumor-using organ-preserving procedures in 49% of patients. This trend is certainly consistent with an increase in such strategies over time and was associated with good sexual quality of life in one study.6,9 Although the incidence of recurrence was 18%, most of the patients could be salvaged with additional organ-preserving procedures. Of note, the local recurrence rate reported was similar to another large center’s recurrence rate in the Netherlands with similar follow-up.9 Management of the inguinal region among the cohort was consistent with previously published guidelines and included observation for good-risk patients, modified lymphadenectomy for high-risk clinically node-negative patients, or inguinal lymphadenectomy with or without pelvic lymphadenectomy based on inguinal node burden.10 Adjuvant chemotherapy or chemoradiotherapy was used based on pathologic risk or documented recurrence. Cancer-specific survival at 5 years was 85% and of course was driven by pathologic extent of disease in the regional lymph nodes. The authors7 provide evidence in this report that they can provide quality care in the management of penile cancer in their region of the United Kingdom. In this regard, this series is typical of early publications reported from other MDT with growing experience in the management of penile cancer as they continue to evolve. Such an evolution should consist of further review of their data, documenting complications of therapy, evaluating strategies to decrease the morbidity of treatment, and partnering with other MDT to develop novel clinical trials in this rare disease. Overall, the growing positive experience with the implementation of supraregional centers in the United Kingdom for the treatment of penile cancer provides the rationale for their implementation in other developed countries. Curtis A. Pettaway, M.D., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX
References 1. National Institute for Clinical Excellence. Penile Cancer. Guidance on Cancer Services. Improving Outcomes in Urological Cancers—The
1102
2.
3.
4.
5.
6.
7.
8.
9.
10.
Manual. London: NICE; 2002:83-85; Available at, http://www.nice. org.uk/guidance/csguc/evidence/improving-outcomes-in-urologicalcancers-manual-2, 2002; Accessed August 1, 2014. Hegarty PK, Kayes O, Freeman A, et al. A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines. BJU Int. 2006;98:526-531. Nicholson S, Hall E, Harland SJ, et al. Phase II trial of docetaxel, cisplatin and 5FUchemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer. 2013;109: 2554-2559. 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;96:1040. Hegarty PK, Shabbir M, Hughes B, et al. Penile preserving surgery and surgical strategies to maximize penile form and function in penile cancer: recommendations from the United Kingdom experience. World J Urol. 2009;27:179. Veeratterapillay R, Sahadevan K, Aluru P, et al. Organ-preserving surgery for penile cancer: description of techniques and surgical outcomes. BJU Int. 2012;110:1792. Veeratterapillay R, Teo L, Asterling S, Greene D. Oncologic outcomes of penile cancer treatment at a UK supraregional center. Urology. 2015;85:1097-1103. Ritchie AW, Foster PW, Fowler S, et al. Penile cancer in the UK: clinical presentation and outcome in 1998/99. BJU Int. 2004;94: 1248. Djajadiningrat RS, van Werkhoven E, Meinhardt W, et al. Penile sparing surgery for penile cancer—does it affect survival? J Urol. 2013. http://dx.doi.org/10.1016/j.juro.2013.12.038; [Epub ahead of print]. Pizzocaro G, Algaba F, Horenblas S, et al. EAU penile cancer guidelines 2009. Eur Urol. 2010;57:1002.
http://dx.doi.org/10.1016/j.urology.2014.11.049 UROLOGY 85: 1101e1102, 2015. Ó 2015 Elsevier Inc.
REPLY There is a very strong case to be made for centralization of penile cancer care in the Western world, where it remains a rare disease. Drawing from the United Kingdom experience, supraregional centers have been set up to manage this condition over the past decade, and there have been a number of groups in the United Kingdom describing their experience at those centers.1-3 In the present study, we report our contemporary outcomes from one such UK center with >200 patients and a median follow-up of just >5 years. We highlight the increased caseload, rise in penile-preserving surgery, multidisciplinary management, and improved oncologic outcomes. Other large centers for penile cancer treatment including the Netherlands have reported similar evolution over time. In addition, with an increasing patient load comes the opportunity to rapidly acquire new experience and to implement and audit new advances in therapy such as dynamic sentinel lymph node biopsy. The dynamic sentinel lymph node biopsy has been shown to be effective and have a low false-negative rate of around 5% in large centers with accumulated experience. It has matured into a reliable and safe method for assessing status of lymph nodes in penile carcinoma patients and has reduced treatment morbidity by improving patient selection for inguinal lymph node dissection.4,5 Further novel techniques have been described for lymph node management in penile cancer including endoscopic and robotic-assisted inguinal lymphadenectomy, and collaboration between penile cancer centers is vital to instigate large-scale clinical trials to test the benefits of those new technologies.6 UROLOGY 85 (5), 2015
UROLOGY 85 (5), 2015
6. Leijte JA, Kroon BK, Valdes Olmos RA, et al. Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma. Eur Urol. 2007;52:170. 7. Pandey D, Mahajan V, Kannan R. Prognostic factors in node-positive carcinoma of the penis. J Surg Oncol. 2006;93:133. 8. Ravi R. Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol. 1993;72:817. 9. Djajadiningrat RS, Graafland NM, van Werkhoven E, et al. Contemporary management of regional nodes in penile cancerimprovement of survival? J Urol. 2014;191:68. 10. Guimaraes GC, Cunha IW, Soares FA, et al. Penile squamous cell carcinoma clinicopathological features, nodal metastasis and outcome in 333 cases. J Urol. 2009;182:528. 11. Moses KA, Winer A, Sfakianos JP, et al. Contemporary management of penile cancer: greater than 15 year MSKCC experience. Can J Urol. 2014;21:7201. 12. National Institute for Health and Clinical Excellence. Improving Outcomes of Urological Cancers. UK. London: NICE; 2003: 83-86. 13. Veeratterapillay R, Sahadevan K, Aluru P, et al. Organ-preserving surgery for penile cancer: description of techniques and surgical outcomes. BJU Int. 2012;110:1792. 14. Coblentz TR, Theodorescu D. Morbidity of modified prophylactic inguinal lymphadenectomy for squamous cell carcinoma of the penis. J Urol. 2002;168:1386. 15. Jacobellis U. Modified radical inguinal lymphadenectomy for carcinoma of the penis: technique and results. J Urol. 2003;169:1349. 16. Pizzocaro G, Algaba F, Horenblas S, et al. EAU penile cancer guidelines 2009. Eur Urol. 2010;57:1002. 17. Ritchie AW, Foster PW, Fowler S, et al. Penile cancer in the UK: clinical presentation and outcome in 1998/99. BJU Int. 2004;94: 1248. 18. Kumar P, Singh S, Goddard JC, et al. The development of a supraregional network for the management of penile cancer. Ann R Coll Surg Engl. 2012;94:204. 19. Arya M, Li R, Pegler K, et al. Long-term trends in incidence, survival and mortality of primary penile cancer in England. Cancer Causes Control. 2013;24:2169. 20. Djajadiningrat RS, van Werkhoven E, Meinhardt W, et al. Penile sparing surgery for penile cancer—does it affect survival? J Urol. 2013. http://dx.doi.org/10.1016/j.juro.2013.12.038; [Epub ahead of print]. 21. Hegarty PK, Eardley I, Heidenreich A, et al. Penile cancer: organsparing techniques. BJU Int. 2013. http://dx.doi.org/10.1111/bju. 12338; [Epub ahead of print]. 22. Leijte JA, Kirrander P, Antonini N, et al. Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients. Eur Urol. 2008;54:161. 23. Lont AP, Kroon BK, Gallee MP, et al. Pelvic lymph node dissection for penile carcinoma: extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol. 2007;177:947. 24. Svatek RS, Munsell M, Kincaid JM, et al. Association between lymph node density and disease specific survival in patients with penile cancer. J Urol. 2009;182:2721. 25. Kroon BK, Horenblas S, Estourgie SH, et al. How to avoid falsenegative dynamic sentinel node procedures in penile carcinoma. J Urol. 2004;171:2191. 26. Tanis PJ, Lont AP, Meinhardt W, et al. Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique. J Urol. 2002;168:76.
EDITORIAL COMMENT Supraregional multidisciplinary teams (MDT) have managed penile cancer in the United Kingdom since the publication of
1101
the National Institute for Clinical Excellence Penile Cancer Guidelines in 2002.1 Such teams serve a catchment area of about 4 million patients and see a minimum of 25 patients per year. Given the rarity of the disease in the United Kingdom and other developed nations, such an approach fosters the delivery of guideline-based approaches to penile cancer management for all patients, multidisciplinary cancer management, clinical research, and the relatively rapid development of expertise among participating physicians in part by increasing patient volume.2-6 In the present study,7 from one such MDT, at Sunderland Royal Hospital, the presenting clinical features, treatment, and outcomes over an 11-year period were retrospectively reviewed. The series consisted of 203 patients with a median follow-up of 5 years. Of note is that the reported cohort is somewhat smaller than the total number seem during that time period due to the lack of complete data on all patients. However, the reported number still represents an average of about 18 seen patients per year. This is significantly more than the 1-2 patients seen per year by the average consultant before institution of the National Institute for Clinical Excellence guidelines.8 The authors managed the primary tumor-using organ-preserving procedures in 49% of patients. This trend is certainly consistent with an increase in such strategies over time and was associated with good sexual quality of life in one study.6,9 Although the incidence of recurrence was 18%, most of the patients could be salvaged with additional organ-preserving procedures. Of note, the local recurrence rate reported was similar to another large center’s recurrence rate in the Netherlands with similar follow-up.9 Management of the inguinal region among the cohort was consistent with previously published guidelines and included observation for good-risk patients, modified lymphadenectomy for high-risk clinically node-negative patients, or inguinal lymphadenectomy with or without pelvic lymphadenectomy based on inguinal node burden.10 Adjuvant chemotherapy or chemoradiotherapy was used based on pathologic risk or documented recurrence. Cancer-specific survival at 5 years was 85% and of course was driven by pathologic extent of disease in the regional lymph nodes. The authors7 provide evidence in this report that they can provide quality care in the management of penile cancer in their region of the United Kingdom. In this regard, this series is typical of early publications reported from other MDT with growing experience in the management of penile cancer as they continue to evolve. Such an evolution should consist of further review of their data, documenting complications of therapy, evaluating strategies to decrease the morbidity of treatment, and partnering with other MDT to develop novel clinical trials in this rare disease. Overall, the growing positive experience with the implementation of supraregional centers in the United Kingdom for the treatment of penile cancer provides the rationale for their implementation in other developed countries. Curtis A. Pettaway, M.D., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX
References 1. National Institute for Clinical Excellence. Penile Cancer. Guidance on Cancer Services. Improving Outcomes in Urological Cancers—The
1102
2.
3.
4.
5.
6.
7.
8.
9.
10.
Manual. London: NICE; 2002:83-85; Available at, http://www.nice. org.uk/guidance/csguc/evidence/improving-outcomes-in-urologicalcancers-manual-2, 2002; Accessed August 1, 2014. Hegarty PK, Kayes O, Freeman A, et al. A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines. BJU Int. 2006;98:526-531. Nicholson S, Hall E, Harland SJ, et al. Phase II trial of docetaxel, cisplatin and 5FUchemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer. 2013;109: 2554-2559. 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;96:1040. Hegarty PK, Shabbir M, Hughes B, et al. Penile preserving surgery and surgical strategies to maximize penile form and function in penile cancer: recommendations from the United Kingdom experience. World J Urol. 2009;27:179. Veeratterapillay R, Sahadevan K, Aluru P, et al. Organ-preserving surgery for penile cancer: description of techniques and surgical outcomes. BJU Int. 2012;110:1792. Veeratterapillay R, Teo L, Asterling S, Greene D. Oncologic outcomes of penile cancer treatment at a UK supraregional center. Urology. 2015;85:1097-1103. Ritchie AW, Foster PW, Fowler S, et al. Penile cancer in the UK: clinical presentation and outcome in 1998/99. BJU Int. 2004;94: 1248. Djajadiningrat RS, van Werkhoven E, Meinhardt W, et al. Penile sparing surgery for penile cancer—does it affect survival? J Urol. 2013. http://dx.doi.org/10.1016/j.juro.2013.12.038; [Epub ahead of print]. Pizzocaro G, Algaba F, Horenblas S, et al. EAU penile cancer guidelines 2009. Eur Urol. 2010;57:1002.
http://dx.doi.org/10.1016/j.urology.2014.11.049 UROLOGY 85: 1101e1102, 2015. Ó 2015 Elsevier Inc.
REPLY There is a very strong case to be made for centralization of penile cancer care in the Western world, where it remains a rare disease. Drawing from the United Kingdom experience, supraregional centers have been set up to manage this condition over the past decade, and there have been a number of groups in the United Kingdom describing their experience at those centers.1-3 In the present study, we report our contemporary outcomes from one such UK center with >200 patients and a median follow-up of just >5 years. We highlight the increased caseload, rise in penile-preserving surgery, multidisciplinary management, and improved oncologic outcomes. Other large centers for penile cancer treatment including the Netherlands have reported similar evolution over time. In addition, with an increasing patient load comes the opportunity to rapidly acquire new experience and to implement and audit new advances in therapy such as dynamic sentinel lymph node biopsy. The dynamic sentinel lymph node biopsy has been shown to be effective and have a low false-negative rate of around 5% in large centers with accumulated experience. It has matured into a reliable and safe method for assessing status of lymph nodes in penile carcinoma patients and has reduced treatment morbidity by improving patient selection for inguinal lymph node dissection.4,5 Further novel techniques have been described for lymph node management in penile cancer including endoscopic and robotic-assisted inguinal lymphadenectomy, and collaboration between penile cancer centers is vital to instigate large-scale clinical trials to test the benefits of those new technologies.6 UROLOGY 85 (5), 2015
