Therapeutic Approaches to Penile Cancer: Standards of Care and Recent Developments

References

• Fu L, Tian T, Yao K, et al. Global pattern and trends in penile cancer incidence: population-based study. JMIR Public Health Surveill. 2022;8(7):e34874. doi:10.2196/34874
   PubMedGoogle Scholar
• Giona S. The epidemiology of penile cancer. In: Barber N, Ali A, editors. Urologic Cancers. Exon Publications; 2022.
   Google Scholar
• Chadha J, Chahoud J, Spiess PE. An update on treatment of penile cancer. Ther Adv Med Oncol. 2022;14:17588359221127254. doi:10.1177/17588359221127254
   Web of Science ®Google Scholar
• Hakenberg OW, Drager DL, Erbersdobler A, Naumann CM, Junemann KP, Protzel C. The diagnosis and treatment of penile cancer. Dtsch Arztebl Int. 2018;115(39):646–652. doi:10.3238/arztebl.2018.0646
   PubMed Web of Science ®Google Scholar
• Tang Y, Hu X, Wu K, Li X. Immune landscape and immunotherapy for penile cancer. Front Immunol. 2022;13:1055235. doi:10.3389/fimmu.2022.1055235
   PubMedGoogle Scholar
• Joshi VB, Chadha J, Chahoud J. Penile cancer: updates in systemic therapy. Asian J Urol. 2022;9(4):374–388. doi:10.1016/j.ajur.2022.03.006
   PubMed Web of Science ®Google Scholar
• Board, PDQ Adult Treatment Editorial. Penile Cancer Treatment (PDQ(R)): health professional version. PDQ Cancer Information Summaries; 2002.
   Google Scholar
• Manjunath A, Brenton T, Wylie S, Corbishley CM, Watkin NA. Topical therapy for non-invasive penile cancer (Tis)-updated results and toxicity. Transl Androl Urol. 2017;6(5):803–808. doi:10.21037/tau.2017.06.24
   PubMed Web of Science ®Google Scholar
• Tang DH, Yan S, Ottenhof SR, et al. Laser ablation as monotherapy for penile squamous cell carcinoma: a multi-center cohort analysis. Urol Oncol. 2018;36(4):147–152. doi:10.1016/j.urolonc.2017.09.028
   PubMed Web of Science ®Google Scholar
• Wikstrom A, Hedblad MA, Johansson B, et al. The acetic acid test in evaluation of subclinical genital papillomavirus infection: a comparative study on penoscopy, histopathology, virology and scanning electron microscopy findings. Genitourin Med. 1992;68(2):90–99. doi:10.1136/sti.68.2.90
   PubMedGoogle Scholar
• Larke NL, Thomas SL, Dos Santos Silva I, Weiss HA. Male circumcision and penile cancer: a systematic review and meta-analysis. Cancer Causes Control. 2011;22(8):1097–1110. doi:10.1007/s10552-011-9785-9
   PubMed Web of Science ®Google Scholar
• Prickett KA, Ramsey ML. Mohs Micrographic Surgery. StatPearls; 2022.
   Google Scholar
• Shindel AW, Mann MW, Lev RY, et al. Mohs micrographic surgery for penile cancer: management and long-term followup. J Urol. 2007;178(5):1980–1985. doi:10.1016/j.juro.2007.07.039
   PubMed Web of Science ®Google Scholar
• Sosnowski R, Kuligowski M, Kuczkiewicz O, et al. Primary penile cancer organ sparing treatment. Cent European J Urol. 2016;69(4):377–383. doi:10.5173/ceju.2016.890
   PubMedGoogle Scholar
• Spiess PE, Necchi A; SpringerLink. Penile Carcinoma: Therapeutic Principles and Advances. 1st ed. Springer International Publishing: Imprint: Springer; 2021.
   Google Scholar
• Falcone M, Preto M, Oderda M, et al. Total glans resurfacing for the management of superficial penile cancer: a retrospective cohort analysis in a tertiary referral center. Urology. 2020;145:281–286. doi:10.1016/j.urology.2020.06.066
   PubMed Web of Science ®Google Scholar
• Lont AP, Gallee MP, Meinhardt W, van Tinteren H, Horenblas S. Penis conserving treatment for T1 and T2 penile carcinoma: clinical implications of a local recurrence. J Urol. 2006;176(2):575–80; discussion 580. doi:10.1016/j.juro.2006.03.063
   PubMed Web of Science ®Google Scholar
• Roussel E, Peeters E, Vanthoor J, et al. Predictors of local recurrence and its impact on survival after glansectomy for penile cancer: time to challenge the dogma? BJU Int. 2021;127(5):606–613. doi:10.1111/bju.15297
   PubMed Web of Science ®Google Scholar
• Hasan S, Francis A, Hagenauer A, et al. The role of brachytherapy in organ preservation for penile cancer: a meta-analysis and review of the literature. Brachytherapy. 2015;14(4):517–524. doi:10.1016/j.brachy.2015.03.008
   PubMed Web of Science ®Google Scholar
• Minhas S, Kayes O, Hegarty P, Kumar P, Freeman A, Ralph D. What surgical resection margins are required to achieve oncological control in men with primary penile cancer? BJU Int. 2005;96(7):1040–1043. doi:10.1111/j.1464-410X.2005.05769.x
   PubMed Web of Science ®Google Scholar
• Brouwer OR, Albersen M, Parnham A, et al. European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 update. Eur Urol. 2023;83(6):548–560. doi:10.1016/j.eururo.2023.02.027
   PubMed Web of Science ®Google Scholar
• Coddington ND, Redger KD, Higuchi TT. Surgical principles of penile cancer for penectomy and inguinal lymph node dissection: a narrative review. AME Med J. 2021;6:29. doi:10.21037/amj-20-159
   Google Scholar
• Kamel MH, Bissada N, Warford R, Farias J, Davis R. Organ sparing surgery for penile cancer: a systematic review. J Urol. 2017;198(4):770–779. doi:10.1016/j.juro.2017.01.088
   PubMed Web of Science ®Google Scholar
• Maddineni SB, Lau MM, Sangar VK. Identifying the needs of penile cancer sufferers: a systematic review of the quality of life, psychosexual and psychosocial literature in penile cancer. BMC Urol. 2009;9:8. doi:10.1186/1471-2490-9-8
   PubMedGoogle Scholar
• Schover LR, von Eschenbach AC, Smith DB, Gonzalez J. Sexual rehabilitation of urologic cancer patients: a practical approach. CA Cancer J Clin. 1984;34(2):66–74. doi:10.3322/canjclin.34.2.66
   PubMed Web of Science ®Google Scholar
• 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(2):179–187. doi:10.1007/s00345-008-0312-x
   PubMed Web of Science ®Google Scholar
• Pizzocaro G, Algaba F, Horenblas S, et al. EAU penile cancer guidelines 2009. Eur Urol. 2010;57(6):1002–1012. doi:10.1016/j.eururo.2010.01.039
   PubMed Web of Science ®Google Scholar
• Stroie FA, Houlihan MD, Kohler TS. Sexual function in the penile cancer survivor: a narrative review. Transl Androl Urol. 2021;10(6):2544–2553. doi:10.21037/tau-20-1228
   PubMed Web of Science ®Google Scholar
• Bandieramonte G, Colecchia M, Mariani L, et al. Peniscopically controlled CO2 laser excision for conservative treatment of in situ and T1 penile carcinoma: report on 224 patients. Eur Urol. 2008;54(4):875–882. doi:10.1016/j.eururo.2008.01.019
   PubMed Web of Science ®Google Scholar
• Windahl T, Skeppner E, Andersson SO, Fugl-Meyer KS. Sexual function and satisfaction in men after laser treatment for penile carcinoma. J Urol. 2004;172(2):648–651. doi:10.1097/01.ju.0000132891.68094.87
   PubMed Web of Science ®Google Scholar
• Hadway P, Corbishley CM, Watkin NA. Total glans resurfacing for premalignant lesions of the penis: initial outcome data. BJU Int. 2006;98(3):532–536. doi:10.1111/j.1464-410X.2006.06368.x
   PubMed Web of Science ®Google Scholar
• Sedigh O, Falcone M, Ceruti C, et al. Sexual function after surgical treatment for penile cancer: which organ-sparing approach gives the best results? Can Urol Assoc J. 2015;9(7–8):E423–E427. doi:10.5489/cuaj.2801
   PubMed Web of Science ®Google Scholar
• Scarberry K, Angermeier KW, Montague D, Campbell S, Wood HM. Outcomes for organ-preserving surgery for penile cancer. Sex Med. 2015;3(2):62–66. doi:10.1002/sm2.56
   PubMed Web of Science ®Google Scholar
• Morelli G, Pagni R, Mariani C, et al. Glansectomy with split-thickness skin graft for the treatment of penile carcinoma. Int J Impot Res. 2009;21(5):311–314. doi:10.1038/ijir.2009.17
   PubMed Web of Science ®Google Scholar
• Perez J, Chavarriaga J, Ortiz A, et al. Oncological and functional outcomes after organ-sparing plastic reconstructive surgery for penile cancer. Urology. 2020;142:161–165 e1. doi:10.1016/j.urology.2020.03.058
   PubMed Web of Science ®Google Scholar
• Chavarriaga J, Becerra L, Camacho D, et al. Inverted urethral flap reconstruction after partial penectomy: long-term oncological and functional outcomes. Urol Oncol. 2022;40(4):169 e13–169 e20. doi:10.1016/j.urolonc.2022.02.006
   PubMed Web of Science ®Google Scholar
• Edward JPFS, Sarah PP, Patricia V, Courtney MPH. Sexual and voiding outcomes in post-penectomy penile cancer patients. JOJ Uro Nephron. 2018;6. doi: 10.19080/JOJUN.2018.06.555678
   Google Scholar
• Kieffer JM, Djajadiningrat RS, van Muilekom EA, Graafland NM, Horenblas S, Aaronson NK. Quality of life for patients treated for penile cancer. J Urol. 2014;192(4):1105–1110. doi:10.1016/j.juro.2014.04.014
   PubMed Web of Science ®Google Scholar
• Romero FR, Romero KR, Mattos MA, Garcia CR, Fernandes Rde C, Perez MD. Sexual function after partial penectomy for penile cancer. Urology. 2005;66(6):1292–1295. doi:10.1016/j.urology.2005.06.081
   PubMed Web of Science ®Google Scholar
• Bhat GS, Nelivigi G, Barude V, Shastry A. Sexuality in Surgically Treated Carcinoma Penis Patients and Their Partners. Indian J Surg. 2018;80(1):19–23. doi:10.1007/s12262-016-1543-5
   PubMed Web of Science ®Google Scholar
• Bickell M, Beilan J, Wallen J, Wiegand L, Carrion R. Advances in surgical reconstructive techniques in the management of penile, urethral, and scrotal cancer. Urol Clin North Am. 2016;43(4):545–559. doi:10.1016/j.ucl.2016.06.015
   PubMed Web of Science ®Google Scholar
• Heyns CF, Fleshner N, Sangar V, Schlenker B, Yuvaraja TB, van Poppel H. Management of the lymph nodes in penile cancer. Urology. 2010;76(2 Suppl 1):S43–S57. doi:10.1016/j.urology.2010.03.001
   PubMed Web of Science ®Google Scholar
• McDougal WS. Preemptive lymphadenectomy markedly improves survival in patients with cancer of the penis who harbor occult metastases. J Urol. 2005;173(3):681. doi:10.1097/01.ju.0000153484.07200.f6
   PubMed Web of Science ®Google Scholar
• Teh J, Duncan C, Qu L, et al. Inguinal lymph node dissection for penile cancer: a contemporary review. Transl Androl Urol. 2020;9(6):3210–3218. doi:10.21037/tau.2019.08.37
   PubMed Web of Science ®Google Scholar
• Pizzocaro G, Piva L, Bandieramonte G, Tana S. Up-to-date management of carcinoma of the penis. Eur Urol. 1997;32(1):5–15. doi:10.1159/000480874
   PubMed Web of Science ®Google Scholar
• Horenblas S. Lymphadenectomy for squamous cell carcinoma of the penis. Part 2: the role and technique of lymph node dissection. BJU Int. 2001;88(5):473–483. doi:10.1046/j.1464-410x.2001.00379.x
   PubMed Web of Science ®Google Scholar
• Saisorn I, Lawrentschuk N, Leewansangtong S, Bolton DM. Fine-needle aspiration cytology predicts inguinal lymph node metastasis without antibiotic pretreatment in penile carcinoma. BJU Int. 2006;97(6):1225–1228. doi:10.1111/j.1464-410X.2006.06159.x
   PubMed Web of Science ®Google Scholar
• Network NCC. Penile cancer (Version 1.2023). Available from: https://www.nccn.org/professionals/physician_gls/pdf/penile.pdf. Accessed January 19, 2023.
   Google Scholar
• Gkegkes ID, Minis EE, Iavazzo C. Robotic-assisted inguinal lymphadenectomy: a systematic review. J Robot Surg. 2019;13(1):1–8. doi:10.1007/s11701-018-0823-4
   PubMed Web of Science ®Google Scholar
• Ottenhof SR, Leone AR, Horenblas S, Spiess PE, Vegt E. Advancements in staging and imaging for penile cancer. Curr Opin Urol. 2017;27(6):612–620. doi:10.1097/MOU.0000000000000447
   PubMed Web of Science ®Google Scholar
• Hughes B, Leijte J, Shabbir M, Watkin N, Horenblas S. Non-invasive and minimally invasive staging of regional lymph nodes in penile cancer. World J Urol. 2009;27(2):197–203. doi:10.1007/s00345-008-0288-6
   PubMed Web of Science ®Google Scholar
• Mueller-Lisse UG, Scher B, Scherr MK, Seitz M. Functional imaging in penile cancer: PET/computed tomography, MRI, and sentinel lymph node biopsy. Curr Opin Urol. 2008;18(1):105–110. doi:10.1097/MOU.0b013e3282f151fd
   PubMed Web of Science ®Google Scholar
• Sadeghi R, Gholami H, Zakavi SR, Kakhki VR, Horenblas S. Accuracy of 18F-FDG PET/CT for diagnosing inguinal lymph node involvement in penile squamous cell carcinoma: systematic review and meta-analysis of the literature. Clin Nucl Med. 2012;37(5):436–441. doi:10.1097/RLU.0b013e318238f6ea
   PubMed Web of Science ®Google Scholar
• Hakenberg OW, Comperat EM, Minhas S, Necchi A, Protzel C, Watkin N. EAU guidelines on penile cancer: 2014 update. Eur Urol. 2015;67(1):142–150. doi:10.1016/j.eururo.2014.10.017
   PubMed Web of Science ®Google Scholar
• Pagliaro LC, Williams DL, Daliani D, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 2010;28(24):3851–3857. doi:10.1200/JCO.2010.29.5477
   PubMed Web of Science ®Google Scholar
• Azizi M, Aydin AM, Hajiran A, et al. Systematic review and meta-analysis-is there a benefit in using neoadjuvant systemic chemotherapy for locally advanced penile squamous cell carcinoma? J Urol. 2020;203(6):1147–1155. doi:10.1097/JU.0000000000000746
   PubMedGoogle Scholar
• Pettaway CA, Nicholson S, Spiess PE, et al. The international penile advanced cancer trial (InPACT): the first phase III trial for squamous carcinoma of the penis with regional lymph node metastases. J Clin Oncol. 2022;40(6_suppl):TPS7–TPS7. doi:10.1200/JCO.2022.40.6_suppl.TPS7
   Google Scholar
• Canter DJ, Nicholson S, Watkin N, Hall E, Pettaway C, In PEC. The International Penile Advanced Cancer Trial (InPACT): rationale and current status. Eur Urol Focus. 2019;5(5):706–709. doi:10.1016/j.euf.2019.05.010
   PubMedGoogle Scholar
• Yuan Z, Naghavi AO, Tang D, et al. The relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer. World J Urol. 2018;36(9):1431–1440. doi:10.1007/s00345-018-2280-0
   PubMed Web of Science ®Google Scholar
• Miralles-Guri C, Bruni L, Cubilla AL, Castellsague X, Bosch FX, de Sanjose S. Human papillomavirus prevalence and type distribution in penile carcinoma. J Clin Pathol. 2009;62(10):870–878. doi:10.1136/jcp.2008.063149
   PubMed Web of Science ®Google Scholar
• Lohneis P, Boral S, Kaufmann AM, et al. Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour-infiltrating T lymphocytes. Virchows Arch. 2015;466(3):323–331. doi:10.1007/s00428-014-1713-4
   PubMed Web of Science ®Google Scholar
• Yugawa T, Kiyono T. Molecular mechanisms of cervical carcinogenesis by high-risk human papillomaviruses: novel functions of E6 and E7 oncoproteins. Rev Med Virol. 2009;19(2):97–113. doi:10.1002/rmv.605
   PubMed Web of Science ®Google Scholar
• Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled Phase 2b trial. Lancet. 2015;386(10008):2078–2088. doi:10.1016/S0140-6736(15)00239-1
   PubMed Web of Science ®Google Scholar
• Chahoud J, Pham R, Sonpavde G. Innovative systemic therapies for penile cancer. Curr Opin Urol. 2022;32(1):8–16. doi:10.1097/MOU.0000000000000941
   PubMed Web of Science ®Google Scholar
• Necchi A, Giannatempo P, Lo Vullo S, et al. Panitumumab treatment for advanced penile squamous cell carcinoma when surgery and chemotherapy have failed. Clin Genitourin Cancer. 2016;14(3):231–236. doi:10.1016/j.clgc.2015.08.001
   PubMed Web of Science ®Google Scholar
• Buonerba C, Di Lorenzo G, Pond G, et al. Prognostic and predictive factors in patients with advanced penile cancer receiving salvage (2nd or Later Line) systemic treatment: a retrospective, multi-center study. Front Pharmacol. 2016;7:487. doi:10.3389/fphar.2016.00487
   PubMed Web of Science ®Google Scholar
• Chahoud J, Tamil M, Necchi A. Second line salvage systemic therapy for advanced penile cancer. Urol Oncol. 2022;40(6):229–234. doi:10.1016/j.urolonc.2020.08.001
   PubMed Web of Science ®Google Scholar
• Jacob JM, Ferry EK, Gay LM, et al. Comparative genomic profiling of refractory and metastatic penile and nonpenile cutaneous squamous cell carcinoma: implications for selection of systemic therapy. J Urol. 2019;201(3):541–548. doi:10.1016/j.juro.2018.09.056
   PubMed Web of Science ®Google Scholar
• Baweja A, Mar N. Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab. J Oncol Pharm Pract. 2021;27(1):212–215. doi:10.1177/1078155220922602
   PubMed Web of Science ®Google Scholar
• Hahn AW, Chahoud J, Campbell MT, et al. Pembrolizumab for advanced penile cancer: a case series from a phase II basket trial. Invest New Drugs. 2021;39(5):1405–1410. doi:10.1007/s10637-021-01100-x
   PubMed Web of Science ®Google Scholar
• Chahoud J, Skelton W, Spiess PE, et al. Case report: two cases of chemotherapy refractory metastatic penile squamous cell carcinoma with extreme durable response to pembrolizumab. Front Oncol. 2020;10:615298. doi:10.3389/fonc.2020.615298
   PubMed Web of Science ®Google Scholar
• Marabelle A, Le DT, Ascierto PA, 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):1–10. doi:10.1200/JCO.19.02105
   PubMed Web of Science ®Google Scholar
• Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353–1365. doi:10.1016/S1470-2045(20)30445-9
   PubMed Web of Science ®Google Scholar
• Group LACO. Pembrolizumab combined with cisplatin-based chemotherapy as first-line systemic therapy in advanced penile cancer; 2022. Available from: https://ClinicalTrials.gov/show/NCT04224740. Accessed January 19, 2023.
   Google Scholar
• Gassian N, Frontczak A, Mouillet G, et al. Activity and tolerability of maintenance avelumab immunotherapy after first line polychemotherapy including platinum in patients with locally advanced or metastatic squamous cell penile carcinoma: PULSE. Bull Cancer. 2020;107(5S):eS16–eS21. doi:10.1016/S0007-4551(20)30282-4
   PubMedGoogle Scholar
• Aydin AM, Hall M, Bunch BL, et al. Expansion of tumor-infiltrating lymphocytes (TIL) from penile cancer patients. Int Immunopharmacol. 2021;94:107481. doi:10.1016/j.intimp.2021.107481
   PubMed Web of Science ®Google Scholar
• Doran SL, Stevanovic S, Adhikary S, et al. T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human, Phase I/II study. J Clin Oncol. 2019;37(30):2759–2768. doi:10.1200/JCO.18.02424
   PubMed Web of Science ®Google Scholar