PURPOSE: To compare Cancer-specific mortality (CSM) in patients with Squamous cell carcinoma (SCC) vs. non-SCC penile cancer, since survival outcomes may differ between histological subtypes. METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2016), penile cancer patients of all stages were identified. Temporal trend analyses, cumulative incidence and Kaplan-Meier plots, multivariable Cox regression and Fine and Gray competing-risks regression analyses tested for CSM differences between non-SCC vs. SCC penile cancer patients. RESULTS: Of 4,120 eligible penile cancer patients, 123 (3%) harbored non-SCC vs. 4,027 (97%) SCC. Of all non-SCC patients, 51 (41%) harbored melanomas, 42 (34%) basal cell carcinomas, 10 (8%) adenocarcinomas, eight (6.5%) skin appendage malignancies, six (5%) epithelial cell neoplasms, two (1.5%) neuroendocrine tumors, two (1.5%) lymphomas, two (1.5%) sarcomas. Stage at presentation differed between non-SCC vs. SCC. In temporal trend analyses, non-SCC diagnoses neither decreased nor increased over time (p > 0.05). After stratification according to localized, locally advanced, and metastatic stage, no CSM differences were observed between non-SCC vs. SCC, with 5-year survival rates of 11 vs 11% (p = 0.9) for localized, 33 vs. 37% (p = 0.4) for locally advanced, and 1-year survival rates of 37 vs. 53% (p = 0.9) for metastatic penile cancer, respectively. After propensity score matching for patient and tumor characteristics and additional multivariable adjustment, no CSM differences between non-SCC vs. SCC were observed. CONCLUSION: Non-SCC penile cancer is rare. Although exceptions exist, on average, non-SCC penile cancer has comparable CSM as SCC penile cancer patients, after stratification for localized, locally invasive, and metastatic disease.

Department of Neurosciences Reproductive Sciences and Odontostomatology University of Naples Federico 2 Naples Italy

Department of Urology 2nd Faculty of Medicine Charles University Prag Czech Republic

Department of Urology and Division of Experimental Oncology URI Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology University Hospital Frankfurt Goethe University Frankfurt Theodor Stern Kai 7 60590 Frankfurt am Main Germany

Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Departments of Urology Weill Cornell Medical College New York NY USA

Division of Urology Cancer Prognostictables and Health Outcomes Unit University of Montréal Health Center Montreal QC Canada

Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

See more in PubMed

Hakenberg OW et al (2018) EAU guidelines on penile cancer

Christodoulidou M, et al. Epidemiology of penile cancer. Curr Probl Cancer. 2015;39(3):126–136. doi: 10.1016/j.currproblcancer.2015.03.010. PubMed DOI

de Martel C, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141(4):664–670. doi: 10.1002/ijc.30716. PubMed DOI PMC

Barnholtz-Sloan JS, et al. Incidence trends in primary malignant penile cancer. Urol Oncol. 2007;25(5):361–367. doi: 10.1016/j.urolonc.2006.08.029. PubMed DOI

Graafland NM, et al. Incidence trends and survival of penile squamous cell carcinoma in the Netherlands. Int J Cancer. 2011;128(2):426–432. doi: 10.1002/ijc.25355. PubMed DOI

Hansen BT, et al. Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956–2015. Int J Cancer. 2018;142(8):1586–1593. doi: 10.1002/ijc.31194. PubMed DOI PMC

Schoffer O, et al. Penile cancer - Incidence, mortality, and survival in Saxony, Germany. Urol Oncol. 2019;37(4):295.e1–295.e8. doi: 10.1016/j.urolonc.2018.12.003. PubMed DOI

Brady KL, Mercurio MG, Brown MD. Malignant tumors of the penis. Dermatol Surg. 2013;39(4):527–547. doi: 10.1111/dsu.12029. PubMed DOI

Moch H, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol. 2016;70(1):93–105. doi: 10.1016/j.eururo.2016.02.029. PubMed DOI

Burt LM, Shrieve DC, Tward JD. Stage presentation, care patterns, and treatment outcomes for squamous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys. 2014;88(1):94–100. doi: 10.1016/j.ijrobp.2013.08.013. PubMed DOI

Mistretta FA, Palumbo C, Knipper S, Mazzone E, Pecoraro A, Tian Z, Musi G, Perrotte P, Montanari E, Shariat SF, Saad F, Briganti A, de Cobelli O, Karakiewicz PI (2020) Conditional survival of patients with stage I-III squamous cell carcinoma of the penis: temporal changes in cancer-specific mortality. World J Urol 38(3):725–732. 10.1007/s00345-019-02869-6 PubMed

Thuret R, et al. (2013) Competing-risks analysis in patients with T1 squamous cell carcinoma of the penis. BJU Int 111(4 Pt B): E174–9. PubMed

Thuret R, et al. Conditional survival predictions after surgery for patients with penile carcinoma. Cancer. 2011;117(16):3723–3730. doi: 10.1002/cncr.25974. PubMed DOI

Thuret R, et al. A population-based analysis of the effect of marital status on overall and cancer-specific mortality in patients with squamous cell carcinoma of the penis. Cancer Causes Control. 2013;24(1):71–79. doi: 10.1007/s10552-012-0091-y. PubMed DOI

Bechara GR, et al. Penile primary melanoma: analysis of six patients treated at Brazilian national cancer institute in the last eight years. Int Braz J Urol. 2013;39(6):823–831. doi: 10.1590/S1677-5538.IBJU.2013.06.08. PubMed DOI

Jabiles AG, et al. Penile melanoma: a 20-year analysis of six patients at the National cancer institute of Peru, Lima. Ecancermedicalscience. 2017;11:731. PubMed PMC

Moses KA, et al. Non-squamous cell carcinoma of the penis: single-center, 15-year experience. World J Urol. 2014;32(5):1347–1353. doi: 10.1007/s00345-013-1216-y. PubMed DOI PMC

Sanchez A, et al. Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort. Urol Oncol. 2016;34(4):166.e7–14. doi: 10.1016/j.urolonc.2015.11.009. PubMed DOI

Sánchez-Ortiz R, et al. Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience. J Urol. 2005;173(6):1958–1965. doi: 10.1097/01.ju.0000159207.91737.53. PubMed DOI

Bhambhvani H, Greenberg D, Parham M, et al. A population-level analysis of nonsquamous penile cancer: the importance of histology. Urol Oncol. 2020 doi: 10.1016/j.urolonc.2020.11.025. PubMed DOI

Wenzel M, Deuker M, Nocera L, Collà Ruvolo C, Tian Z, Shariat SF, Saad F, Briganti A, Becker A, Kluth LA, Chun FKH, Karakiewicz PI. Comparison between urothelial and non urothelial urethral cancer. Front Oncol. 2021;29(10):629692. doi: 10.3389/fonc.2020.629692. PubMed DOI PMC

Deuker M, Stolzenbach LF, Collà Ruvolo C, Nocera L, Tian Z, Roos FC, Becker A, Kluth LA, Tilki D, Shariat SF, Saad F, Chun FKH, Karakiewicz PI. Upper urinary tract tumors: variant histology versus urothelial carcinoma. Clin Genitourin Cancer. 2021;19(2):117–124. doi: 10.1016/j.clgc.2020.11.004. PubMed DOI

Deuker M, Stolzenbach LF, Collà Ruvolo C, Nocera L, Mansour M, Tian Z, Roos FC, Becker A, Kluth LA, Tilki D, Shariat SF, Saad F, Chun FKH, Karakiewicz PI. Micropapillary versus urothelial carcinoma of the urinary bladder: stage at presentation and efficacy of chemotherapy across all stages-A SEER-based study. Eur Urol Focus. 2020 doi: 10.1016/j.euf.2020.08.010. PubMed DOI

Nocera L, Collà Ruvolo C, Stolzenbach LF, Wenzel M, Tian Z, Larcher A, Capitanio U, Mirone V, Tilki D, Chun FKH, Kapoor A, Shariat SF, Saad F, Montorsi F, Briganti A, Karakiewicz PI. Tumor stage and substage predict cancer-specific mortality after nephrectomy for nonmetastatic renal cancer: histological subtype-specific validation. Eur Urol Focus. 2021 doi: 10.1016/j.euf.2021.02.009. PubMed DOI

National Cancer Institute. Overview of the SEER program. [Cited 2021] Available from https://seer.cancer.gov/about/overview.html

World Health Organization, International Classification of Diseases for Oncology (2013) In: Fritz A et al (eds)

Sobin L, Wittekind C (2011) TNM classificaiton of malignant tumours, 7th edn

Wenzel M, Nocera L, Collà Ruvolo C, Würnschimmel C, Tian Z, Shariat SF, Saad F, Briganti A, Tilki D, Mandel P, Becker A, Kluth LA, Chun FKH, Karakiewicz PI. Incidence rates and contemporary trends in primary urethral cancer. Cancer Causes Control. 2021 doi: 10.1007/s10552-021-01416-2. PubMed DOI PMC

Wenzel M, Würnschimmel C, Ruvolo CC, Nocera L, Tian Z, Saad F, Briganti A, Tilki D, Graefen M, Kluth LA, Mandel P, Chun FKH, Karakiewicz PI. Increasing rates of NCCN high and very high-risk prostate cancer versus number of prostate biopsy cores. Prostate. 2021;81(12):874–881. doi: 10.1002/pros.24184. PubMed DOI

Dotan ZA, et al. Adult genitourinary sarcoma: the 25-year Memorial Sloan-Kettering experience. J Urol. 2006;176(5):2033–2038. doi: 10.1016/j.juro.2006.07.021. PubMed DOI

Mondaini N, et al. Clinical characteristics and overall survival in genitourinary sarcomas treated with curative intent: a multicenter study. Eur Urol. 2005;47(4):468–473. doi: 10.1016/j.eururo.2004.09.013. PubMed DOI

Nazemi A, Daneshmand S. Adult genitourinary sarcoma: a population-based analysis of clinical characteristics and survival. Urol Oncol. 2020;38(5):334–343. doi: 10.1016/j.urolonc.2019.12.004. PubMed DOI

Arya M, et al. Long-term trends in incidence, survival and mortality of primary penile cancer in England. Cancer Causes Control. 2013;24(12):2169–2176. doi: 10.1007/s10552-013-0293-y. PubMed DOI

Baldur-Felskov B, et al. Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978–2008: a nationwide population-based study. Cancer Causes Control. 2012;23(2):273–280. doi: 10.1007/s10552-011-9876-7. PubMed DOI