AccScience Publishing / EJMO / Volume 7 / Issue 1 / DOI: 10.14744/ejmo.2023.43161
CASE REPORT

Immunotherapy Combined with Microwave Ablation and Radiotherapy Reversed the Biological Behavior of Penile Squamous Cell Carcinoma: A Case Report and Literature Review

Liang Xiao1 Xinliang Zhong1,2 Lin Lin1 Chang’e Jin3 Peng Zhou4 ZeQiang Zhou1
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1 Department of Surgery and Oncology, Shenzhen Second People’s Hospital, First Affiliated Hospital to Shenzhen University, Shenzhen, Guangdong, China
2 Southern University of Science and Technology Hospital, Shenzhen, Guangdong, China
3 Department of Respiratory and Critical Care Medicine, Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
4 Department of Ultrasound, Shenzhen Second People’s Hospital, First Affiliated Hospital to Shenzhen University, Shenzhen, Guangdong, China
Submitted: 21 January 2023 | Revised: 24 February 2023 | Accepted: 26 February 2023 | Published: 8 March 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Penile squamous cell carcinoma (pSCC) is a rare malignancy of urinary system. Patients with advanced and metastasized pSCC are associated with poor prognosis due to the limited treatments options of pSCC. In our case report, we describe a patient diagnosed with early stage (stage IIA) and well differentiated pSCC. However, the well differentiated penile squamous cell carcinoma had showed an unexpected aggressiveness. The patient had two times rapid relapse with local advanced and metastasis after two radical operation. As received multimodal treatments including chemotherapy, immunotherapy and local ablation therapy and radiotherapy, the patient had got progression free survival (PFS) exceeding 26 months and overall survival (OS) exceeding 44 months. Immunotherapy combined with ablation therapy and radiotherapy may reverse the biological behavior of penile squamous cell carcinoma.

Keywords
Immunotherapy
microwave ablation (MWA)
multimodal treatments
penile cancer
penile squamous cell carcinoma (pSCC)
radiotherapy
Conflict of interest
None declared.
References

1. Hakenberg OW, Dräger DL, Erbersdobler A, Naumann CM, Jünemann KP, Protzel C. The diagnosis and treatment of penile cancer. Dtsch Arztebl Int 2018 ;115:646-52.
2. Ficarra V, Akduman B, Bouchot O, Palou J, Tobias-Machado M. Prognostic factors in penile cancer. Urology 2010;76:S66-73.
3. Graafland NM, Lam W, Leijte JA, Yap T, Gallee MP, Corbishley C, et al. Prognostic factors for occult inguinal lymph node involvement in penile carcinoma and assessment of the highrisk EAU subgroup: a two-institution analysis of 342 clinically node-negative patients. Eur Urol 2010;58:742-7.
4. Pettaway CA, Horenblas S. Penile cancer: incremental insights into etiology, diagnosis, staging, and management. World J Urol 2009;27:139-40.
5. Pagliaro LC, Crook J. Multimodality therapy in penile cancer: when and which treatments? World J Urol 2009;27:221-5.
6. Pettaway CA, Pagliaro L, Theodore C, Haas G. Treatment of visceral, unresectable, or bulky/unresectable regional metastases of penile cancer. Urology 2010;76:S58-65. 
7. Necchi A, Pond GR, Raggi D, Ottenhof SR, Djajadiningrat RS, Horenblas S, et al. Clinical outcomes of perioperative chemotherapy in patients with locally advanced penile squamouscell carcinoma: results of a multicenter analysis. Clin Genitourin Cancer 2017;15:548-55.e3.
8. Pagliaro LC, Williams DL, Daliani D, Williams MB, Osai W, Kincaid M, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol 2010;28:3851-7.
9. Dickstein RJ, Munsell MF, Pagliaro LC, Pettaway CA. Prognostic factors influencing survival from regionally advanced squamous cell carcinoma of the penis after preoperative chemotherapy. BJU Int 2016;117:118-25.
10. Bermejo C, Busby JE, Spiess PE, Heller L, Pagliaro LC, Pettaway CA. Neoadjuvant chemotherapy followed by aggressive surgical consolidation for metastatic penile squamous cell carcinoma. J Urol 2007;177:1335-8.
11. Hakenberg OW, Nippgen JB, Froehner M, Zastrow S, Wirth MP. Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma. BJU Int 2006;98:1225-7.
12. Haas GP, Blumenstein BA, Gagliano RG, Russell CA, Rivkin SE, Culkin DJ, et al. Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol 1999;161:1823-5.
13. Xu J, Li G, Zhu SM, Cai QL, Wang Z, Yang X, et al. Neoadjuvant docetaxel, cisplatin and ifosfamide (ITP) combination chemotherapy for treating penile squamous cell carcinoma patients with terminal lymph node metastasis. BMC Cancer 2019;19:625.
14. Nicolai N, Sangalli LM, Necchi A, Giannatempo P, Paganoni AM, Colecchia M, et al. A Combination of cisplatin and 5-fluorouracil with a taxane in patients who underwent lymph node dissection for nodal metastases from squamous cell carcinoma of the penis: treatment outcome and survival analyses in neoadjuvant and adjuvant settings. Clin Genitourin Cancer 2016;14:323-30.
15. Di Lorenzo G, Federico P, Buonerba C, Longo N, Cartenì G, Autorino R, et al. Paclitaxel in pretreated metastatic penile cancer: final results of a phase 2 study. Eur Urol 2011;60:1280-4.
16. Nicholson S, Hall E, Harland SJ, Chester JD, Pickering L, Barber J, et al. Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer 2013;109:2554-9.
17. Theodore C, Skoneczna I, Bodrogi I, Leahy M, Kerst JM, Collette L, et al; EORTC Genito-Urinary Tract Cancer Group. A phase II multicentre study of irinotecan (CPT 11) in combination with cisplatin (CDDP) in metastatic or locally advanced penile carcinoma (EORTC PROTOCOL 30992). Ann Oncol 2008;19:1304- 7.
18. Wang J, Pettaway CA, Pagliaro LC. Treatment for metastatic penile cancer after first-line chemotherapy failure: analysis of response and survival outcomes. Urology 2015;85:1104-10.
19. Power DG, Galvin DJ, Cuffe S, McVey GP, Mulholland PJ, Farrelly C, et al. Cisplatin and gemcitabine in the management of metastatic penile cancer. Urol Oncol 2009;27:187-90.
20. Men HT, Gou HF, Qiu M, He JP, Cheng K, Chen Y, et al. A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy. Anticancer Drugs 2014;25:123-5.
21. Carthon BC, Ng CS, Pettaway CA, Pagliaro LC. Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis. BJU Int 2014;113:871-7.
22. Necchi A, Nicolai N, Colecchia M, Catanzaro M, Torelli T, Piva L, et al. Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis. J Clin Oncol 2011;29:e650-2.
23. Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, et al. Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol 2017;18:1104-15.
24. Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med 2018;379:341-51.
25. Cocks M, Taheri D, Ball MW, Bezerra SM, Del Carmen Rodriguez M, Ricardo BFP, et al. Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. Hum Pathol 2017;59:55-61.
26. Udager AM, Liu TY, Skala SL, Magers MJ, McDaniel AS, Spratt DE, et al. Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches. Ann Oncol 2016;27:1706- 12.
27. Djajadiningrat RS, Bergman AM, van Werkhoven E, Vegt E, Horenblas S. Neoadjuvant taxane-based combination chemotherapy in patients with advanced penile cancer. Clin Genito-urin Cancer 2015;13:44-9.
28. Noronha V, Patil V, Ostwal V, Tongaonkar H, Bakshi G, Prabhash K. Role of paclitaxel and platinum-based adjuvant chemotherapy in high-risk penile cancer. Urol Ann 2012;4:150-3.
29. Zhu Y, Li H, Yao XD, Zhang SL, Zhang HL, Shi GH, et al. Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report. Urol Int 2010;85:334-40.
30. Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997;15:2040-9.
31. Parthasarathy A, Cheung MK, Osann K, Husain A, Teng NN, Berek JS, et al. The benefit of adjuvant radiation therapy in single-node-positive squamous cell vulvar carcinoma. Gynecol Oncol 2006;103:1095-9.
32. Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013;31:845-52.
33. Stehman FB, Ali S, Keys HM, Muderspach LI, Chafe WE, Gallup DG, et al. Radiation therapy with or without weekly cisplatin for bulky stage 1B cervical carcinoma: follow-up of a Gynecologic Oncology Group trial. Am J Obstet Gynecol 2007;197:503.e1-6.
34. Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 1986;68:733-40.
35. Franks KN, Kancherla K, Sethugavalar B, Whelan P, Eardley I, Kiltie AE. Radiotherapy for node positive penile cancer: experience of the Leeds teaching hospitals. J Urol 2011;186:524-9.
36. Tang DH, Djajadiningrat R, Diorio G, Chipollini J, Ma Z, Schaible BJ, et al. Adjuvant pelvic radiation is associated with improved survival and decreased disease recurrence in pelvic nodepositive penile cancer after lymph node dissection: A multiinstitutional study. Urol Oncol 2017;35:605.e17-605.e23.
37. 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 2018;36:92.e11-92.e16.
38. Johnstone PAS, Boulware D, Djajadiningrat R, Ottenhof S, Necchi A, Catanzaro M, et al. Primary penile cancer: the role of adjuvant radiation therapy in the management of extranodal extension in lymph nodes. Eur Urol Focus 2019;5:737-41.
39. Aggen DH, Drake CG. Biomarkers for immunotherapy in bladder cancer: a moving target. J Immunother Cancer 2017;5:94.
40. Deng C, Li Z, Guo S, Chen P, Chen X, Zhou Q, et al. Tumor PDL1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma. Oncoimmunology 2016;6:e1269047.
41. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-8.
42. Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N Engl J Med 2017;377:2500-1.
43. Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De JesusAcosta A, Delord JP, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/ mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 Study. J Clin Oncol 2020;38:1-10.
44. Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 2017;9:34.
45. Zhang Y, Deng J, Feng J, Wu F. Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound. World J Gastroenterol 2010;16:3584-91.
46. Deng J, Zhang Y, Feng J, Wu F. Dendritic cells loaded with ultrasound-ablated tumour induce in vivo specific antitumour immune responses. Ultrasound Med Biol 2010;36:441-8. 
47. Xia JZ, Xie FL, Ran LF, Xie XP, Fan YM, Wu F. High-intensity focused ultrasound tumor ablation activates autologous tumor-specific cytotoxic T lymphocytes. Ultrasound Med Biol 2012;38:1363-71.
48. Shi L, Chen L, Wu C, Zhu Y, Xu B, Zheng X, et al. PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor. Clin Cancer Res 2016;22:1173-84. 
49. Battaglia A, Buzzonetti A, Martinelli E, Fanelli M, Petrillo M, Ferrandina G, et al. Selective changes in the immune profile of tumor-draining lymph nodes after different neoadjuvant chemoradiation regimens for locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 2010;76:1546-53.
50. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys 2012;83:1306-10. 
51. Hou Y, Liang HL, Yu X, Liu Z, Cao X, Rao E, et al. Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity. Sci Transl Med 2021;13:eabb0130.
52. Reddy JP, Pettaway CA, Levy LB, Pagliaro LC, Tamboli P, Rao P, Jayaratna I, Hoffman KE. Factors associated with regional recurrence after lymph node dissection for penile squamous cell carcinoma. BJU Int 2017;119:591-7. 

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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing