More lymph node dissection improves survival in patients with newly diagnosed lymph node-positive penile cancer
Abstract
Purpose
For patients with lymph node-positive (LN+) penile cancer, the optimal extent of lymph node dissection (LND) is currently not established. We aimed to reveal the potential association between survival and the number of LND in patients with newly diagnosed LN + penile cancer.
Methods
Patients with LN + penile cancer diagnosed between 2004 and 2015 were identified using the SEER database. The relationships between the number of removed lymph nodes and overall survival (OS), all-cause mortality (ACM), cancer-specific mortality (CSM), and 5-year mortality were tested. Kaplan–Meier curves as well as univariate and multivariable cox regression were used to further analyze disparities in mortality and survival.
Results
Among 599 eligible patients with LN + penile cancer, 527 (88.0%) received surgery and 72 (12.0%) did not. Compared with those who had not received surgery, patients receiving surgery had longer overall survival (28.31 ± 30.84 versus 16.69 ± 21.68 months) and longer median survival (15.00 versus 8.00 months) times. Univariate analyses demonstrated the number of LND to be an independent factor. Multivariable Cox regression analyses suggested that the ≥ 8 removed lymph nodes predicted a lower ACM rate (hazard ratio (HR) = 0.48, 95% CI 0.38–0.61, p < 0.001), penile CSM rate (HR = 0.42, 95% CI 0.30–0.57, p < 0.001), and lower 5-year mortality (HR = 0.58, 95% CI 0.47–0.71, p < 0.001).
Conclusions
In patients with newly diagnosed LN + penile cancer, more LND during lymphadenectomy was associated with an improvement in ACM, CSM rate, and 5-year mortality. Therefore, patients with preoperatively LN + penile cancer should undergo LND to have more lymph nodes removed.
Keywords
Penile cancer Lymph node dissection Lymph node-positive Survival benefits SEERAbbreviations
- LN+
Lymph node-positive
- LND
Lymph node dissection
- OS
Overall survival
- ACM
All-cause mortality
- CSM
Cancer-specific mortality
- SEER
Surveillance, Epidemiology, and End Results
Notes
Author contributions
WM, JF, and JG were involved in the study conception and design. WM, JG collected and assembled data. WM, JF, and JG were involved in data analysis and interpretation WM, XH, and MK wrote the manuscript.
Funding
This work was supported by grant 1501219143 and 81001134 to Jiang Geng.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Supplementary material
References
- 1.Chaux A, Netto GJ, Rodriguez IM, Barreto JE, Oertell J, Ocampos S et al (2013) Epidemiologic profile, sexual history, pathologic features, and human papillomavirus status of 103 patients with penile carcinoma. World J Urol 31(4):861–867. https://doi.org/10.1007/s00345-011-0802-0 CrossRefGoogle Scholar
- 2.Salazar A, Junior EP, Salles PGO, Silva-Filho R, Reis EA, Mamede M (2018) (18)F-FDG PET/CT as a prognostic factor in penile cancer. Eur J Nucl Med Mol Imaging. https://doi.org/10.1007/s00259-018-4128-7 Google Scholar
- 3.Barski D, Georgas E, Gerullis H, Ecke T (2014) Metastatic penile carcinoma: an update on the current diagnosis and treatment options. Cent Eur J Urol 67(2):126–132. https://doi.org/10.5173/ceju.2014.02.art2 Google Scholar
- 4.Curado M (2002) Cancer incidence in five continents (Volume VIII). IARC Scientific Publications, Lyon 155:1–781Google Scholar
- 5.Shabbir M, Minhas S, Muneer A (2011) Diagnosis and management of premalignant penile lesions. Ther Adv Urol 3(3):151–158. https://doi.org/10.1177/1756287211412657 CrossRefGoogle Scholar
- 6.Ottenhof SR, Djajadiningrat RS, Thygesen HH, Jakobs PJ, Jozwiak K, Heeren AM et al (2018) The prognostic value of immune factors in the tumor microenvironment of penile squamous cell carcinoma. Front Immunol 9:1253. https://doi.org/10.3389/fimmu.2018.01253 CrossRefGoogle Scholar
- 7.Kirrander P, Sherif A, Friedrich B, Lambe M, Hakansson U, Steering Committee of the Swedish National Penile Cancer R (2016) Swedish National Penile Cancer Register: incidence, tumour characteristics, management and survival. BJU Int 117(2):287–292. https://doi.org/10.1111/bju.12993 CrossRefGoogle Scholar
- 8.Leone A, Diorio GJ, Pettaway C, Master V, Spiess PE (2017) Contemporary management of patients with penile cancer and lymph node metastasis. Nat Rev Urol 14(6):335–347. https://doi.org/10.1038/nrurol.2017.47 CrossRefGoogle Scholar
- 9.Ficarra V, Akduman B, Bouchot O, Palou J, Tobias-Machado M (2010) Prognostic factors in penile cancer. Urology 76(2 Suppl 1):S66–S73. https://doi.org/10.1016/j.urology.2010.04.008 CrossRefGoogle Scholar
- 10.Horenblas S (2001) Lymphadenectomy for squamous cell carcinoma of the penis. Part 2: the role and technique of lymph node dissection. BJU Int 88(5):473–483CrossRefGoogle Scholar
- 11.Martin AM, Cagney DN, Catalano PJ, Warren LE, Bellon JR, Punglia RS et al (2017) Brain metastases in newly diagnosed breast cancer: a population-based study. JAMA Oncol 3(8):1069–1077. https://doi.org/10.1001/jamaoncol.2017.0001 CrossRefGoogle Scholar
- 12.Gupta A, Atoria CL, Ehdaie B, Shariat SF, Rabbani F, Herr HW et al (2014) Risk of fracture after radical cystectomy and urinary diversion for bladder cancer. J Clin Oncol 32(29):3291–3298. https://doi.org/10.1200/JCO.2013.54.3173 CrossRefGoogle Scholar
- 13.Chamie K, Litwin MS, Bassett JC, Daskivich TJ, Lai J, Hanley JM et al (2013) Recurrence of high-risk bladder cancer: a population-based analysis. Cancer 119(17):3219–3227. https://doi.org/10.1002/cncr.28147 CrossRefGoogle Scholar
- 14.Compton CC, Byrd DR, Garciaaguilar J, Kurtzman SH, Olawaiye A (2012) AJCC cancer staging atlas. Springer, BerlinCrossRefGoogle Scholar
- 15.Backes DM, Kurman RJ, Pimenta JM, Smith JS (2009) Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control: CCC 20(4):449–457. https://doi.org/10.1007/s10552-008-9276-9 CrossRefGoogle Scholar
- 16.Parkin DM, Bray F. Chapter (2006) The burden of HPV-related cancers. Vaccine 2(24 Suppl 3):S3/11–25. https://doi.org/10.1016/j.vaccine.2006.05.111 CrossRefGoogle Scholar
- 17.Correa AF, Handorf E, Joshi SS, Geynisman DM, Kutikov A, Chen DY et al (2018) Differences in survival associated with performance of lymph node dissection in patients with invasive penile cancer: results from the National Cancer Database. J Urol 199(5):1238–1244. https://doi.org/10.1016/j.juro.2017.11.121 CrossRefGoogle Scholar
- 18.Sanchez-Ortiz RF, Pettaway CA (2004) The role of lymphadenectomy in penile cancer. Urol Oncol 22(3):236–244. https://doi.org/10.1016/j.urolonc.2004.04.031. discussion 44 – 5.CrossRefGoogle Scholar
- 19.Alnajjar HM, Lam W, Bolgeri M, Rees RW, Perry MJ, Watkin NA (2012) Treatment of carcinoma in situ of the glans penis with topical chemotherapy agents. Eur Urol 62(5):923–928. https://doi.org/10.1016/j.eururo.2012.02.052 CrossRefGoogle Scholar
- 20.Liu JY, Li YH, Zhang ZL, Yao K, Ye YL, Xie D et al (2013) The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection. World J Urol 31(6):1519–1524. https://doi.org/10.1007/s00345-013-1024-4 CrossRefGoogle Scholar
- 21.Lont AP, Kroon BK, Gallee MP, van Tinteren H, Moonen LM, Horenblas S (2007) 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 177(3):947–952. https://doi.org/10.1016/j.juro.2006.10.060. discussion 52CrossRefGoogle Scholar
- 22.Joshi SS, Handorf E, Strauss D, Correa AF, Kutikov A, Chen DYT et al (2018) Treatment trends and outcomes for patients with lymph node-positive cancer of the penis. JAMA Oncol 4(5):643–649. https://doi.org/10.1001/jamaoncol.2017.5608 CrossRefGoogle Scholar
- 23.Leijte JA, Kerst JM, Bais E, Antonini N, Horenblas S (2007) Neoadjuvant chemotherapy in advanced penile carcinoma. Eur Urol 52(2):488–494. https://doi.org/10.1016/j.eururo.2007.02.006 CrossRefGoogle Scholar
- 24.Winters BR, Kearns JT, Holt SK, Mossanen M, Lin DW, Wright JL. Is there a benefit to adjuvant radiation in stage III penile cancer after lymph node dissection? Findings from the National Cancer Database. Urol Oncol. 2017;36(3)Google Scholar
- 25.Ornellas AA, Kinchin EW, Nobrega BL, Wisnescky A, Koifman N, Quirino R (2008) Surgical treatment of invasive squamous cell carcinoma of the penis: Brazilian National Cancer Institute long-term experience. J Surg Oncol 97(6):487–495. https://doi.org/10.1002/jso.20980 CrossRefGoogle Scholar
- 26.Kumar V, Sethia KK (2017) Prospective study comparing video-endoscopic radical inguinal lymph node dissection (VEILND) with open radical ILND (OILND) for penile cancer over an 8-year period. BJU Int 119(4):530–534. https://doi.org/10.1111/bju.13660 CrossRefGoogle Scholar
- 27.Yao K, Tu H, Li YH, Qin ZK, Liu ZW, Zhou FJ et al (2010) Modified technique of radical inguinal lymphadenectomy for penile carcinoma: morbidity and outcome. J Urol 184(2):546–552. https://doi.org/10.1016/j.juro.2010.03.140 CrossRefGoogle Scholar
- 28.Herr HW, Bochner BH, Dalbagni G, Donat SM, Reuter VE, Bajorin DF (2002) Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 167(3):1295–1298CrossRefGoogle Scholar
- 29.Ide H, Kikuchi E, Miyajima A, Nakagawa K, Ohigashi T, Nakashima J et al (2008) The predictors of local recurrence after radical cystectomy in patients with invasive bladder cancer. Jpn J Clin Oncol 38(5):360–364. https://doi.org/10.1093/jjco/hyn036 CrossRefGoogle Scholar
- 30.Leissner J, Hohenfellner R, Thuroff JW, Wolf HK (2000) Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis. BJU Int 85(7):817–823CrossRefGoogle Scholar
- 31.Herr HW (2003) Extent of surgery and pathology evaluation has an impact on bladder cancer outcomes after radical cystectomy. Urology 61(1):105–108CrossRefGoogle Scholar
- 32.Abdollah F, Gandaglia G, Suardi N, Capitanio U, Salonia A, Nini A et al (2015) More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer. Eur Urol 67(2):212–219. https://doi.org/10.1016/j.eururo.2014.05.011 CrossRefGoogle Scholar
- 33.Poulsen AL, Horn T, Steven K (1998) Radical cystectomy: extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer confined to the bladder wall. The J Urol 160(6 Pt 1):2015–2019; discussion 20Google Scholar