Factors Predictive of Recurrence, Metastasis and Death in Node-negative Penile Squamous Cell Carcinoma: A Retrospective Multicentre Cohort Study

Overview

Journal J Eur Acad Dermatol Venereol

Specialty Infectious Diseases

Date 2024 Jun 6

PMID 38842227

Authors

Katie A OConnell

Jacob L Thomas

Fadi Murad

Guohai Zhou

Guru P Sonpavde

Matthew Mossanen

Timothy N Clinton

Antonio Ji-Xu

Philippe E Spiess

Anthony M Rossi

Chrysalyne D Schmults

Affiliations

Soon will be listed here.

Abstract

Background: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis.

Objectives: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy.

Methods: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed.

Results: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22).

Conclusions: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

References

Li Z, Li X, Lam W, Cao Y, Geng J, Ornellas A . Corpora Cavernos invasion vs. Corpus Spongiosum invasion in Penile Cancer: A systematic review and meta-analysis. J Cancer. 2021; 12(7):1960-1966. PMC: 7974529. DOI: 10.7150/jca.56504. View

Sun M, Djajadiningrat R, Alnajjar H, Trinh Q, Graafland N, Watkin N . Development and external validation of a prognostic tool for prediction of cancer-specific mortality after complete loco-regional pathological staging for squamous cell carcinoma of the penis. BJU Int. 2014; 116(5):734-43. DOI: 10.1111/bju.12677. View

Hu J, Cui Y, Liu P, Zhou X, Ren W, Chen J . Predictors of inguinal lymph node metastasis in penile cancer patients: a meta-analysis of retrospective studies. Cancer Manag Res. 2019; 11:6425-6441. PMC: 6628149. DOI: 10.2147/CMAR.S206579. View

Guimaraes M, Macieira R, Azevedo F, Lisboa C . Association between HPV infection and penile cancer and penile intraepithelial neoplasia: A retrospective observational study. J Eur Acad Dermatol Venereol. 2023; 38(1):186-190. DOI: 10.1111/jdv.19393. View

Zhu Y, Gu W, Xiao W, Wang B, Azizi M, Spiess P . Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines. Ann Surg Oncol. 2018; 26(2):685-691. DOI: 10.1245/s10434-018-7066-5. View

Wen S, Ren W, Xue B, Fan Y, Jiang Y, Zeng C . Prognostic factors in patients with penile cancer after surgical management. World J Urol. 2018; 36(3):435-440. DOI: 10.1007/s00345-017-2167-5. View

Schmults C, Karia P, Carter J, Han J, Qureshi A . Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 2013; 149(5):541-7. DOI: 10.1001/jamadermatol.2013.2139. View

Douglawi A, Masterson T . Penile cancer epidemiology and risk factors: a contemporary review. Curr Opin Urol. 2018; 29(2):145-149. DOI: 10.1097/MOU.0000000000000581. View

Kearns J, Winters B, Holt S, Mossanen M, Lin D, Wright J . Pathologic Nodal Involvement in Patients With Penile Cancer With Cavernosal Versus Spongiosal Involvement. Clin Genitourin Cancer. 2018; 17(1):e156-e161. DOI: 10.1016/j.clgc.2018.10.004. View

10.

Winters B, Mossanen M, Holt S, Lin D, Wright J . Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis. Urology. 2016; 96:29-34. DOI: 10.1016/j.urology.2016.06.033. View

11.

Veeratterapillay R, Teo L, Asterling S, Greene D . Oncologic Outcomes of Penile Cancer Treatment at a UK Supraregional Center. Urology. 2015; 85(5):1097-1103. DOI: 10.1016/j.urology.2014.11.048. View

12.

Zhang W, Gao P, Gao J, Wu X, Liu G, Zhang X . A Clinical Nomogram for Predicting Lymph Node Metastasis in Penile Cancer: A SEER-Based Study. Front Oncol. 2021; 11:640036. PMC: 7985344. DOI: 10.3389/fonc.2021.640036. View

13.

Morris B, Kennedy S, Wodak A, Mindel A, Golovsky D, Schrieber L . Early infant male circumcision: Systematic review, risk-benefit analysis, and progress in policy. World J Clin Pediatr. 2017; 6(1):89-102. PMC: 5296634. DOI: 10.5409/wjcp.v6.i1.89. View

14.

Chen X, Li X, Garcia M, Gong K, Song Y, He Z . Prognostic factors in Chinese patients with penile invasive squamous cell carcinoma. J Androl. 2012; 33(6):1276-81. DOI: 10.2164/jandrol.112.016378. View

15.

Chaux A, Caballero C, Soares F, Guimaraes G, Cunha I, Reuter V . The prognostic index: a useful pathologic guide for prediction of nodal metastases and survival in penile squamous cell carcinoma. Am J Surg Pathol. 2009; 33(7):1049-57. DOI: 10.1097/PAS.0b013e31819d17eb. View

16.

Campbell R, Slopnick E, Ferry E, Zhu H, Kim S, Abouassaly R . Disparity between pre-existing management of penile cancer and NCCN guidelines. Urol Oncol. 2017; 35(8):531.e9-531.e14. DOI: 10.1016/j.urolonc.2017.03.002. View

17.

Qu X, Siemens D, Louie A, Yip D, Mahmud A . Validation of predictors for lymph node status in penile cancer: Results from a population-based cohort. Can Urol Assoc J. 2018; 12(4):119-125. PMC: 5905539. DOI: 10.5489/cuaj.4711. View

18.

Zhou X, Qi F, Zhou R, Wang S, Wang Y, Wang Y . The role of perineural invasion in penile cancer: a meta-analysis and systematic review. Biosci Rep. 2018; 38(5). PMC: 6209582. DOI: 10.1042/BSR20180333. View

19.

Termini L, Fregnani J, Boccardo E, da Costa W, Longatto-Filho A, Andreoli M . SOD2 immunoexpression predicts lymph node metastasis in penile cancer. BMC Clin Pathol. 2015; 15:3. PMC: 4350326. DOI: 10.1186/s12907-015-0003-7. View

20.

Sali A, Menon S, Prakash G, Murthy V, Bakshi G, Mahantshetty U . Histopathological risk scoring system as a tool for predicting lymph nodal metastasis in penile squamous cell carcinoma. Pathology. 2019; 51(7):696-704. DOI: 10.1016/j.pathol.2019.08.003. View