Guideline sources The following summarized guidelines for the evaluation and management of penile cancer are prepared by our editorial team based on guidelines from the European Association of Urology (EAU 2018) and the European Society of Medical Oncology (ESMO 2013). 1 2 Calculator Calculator Calculat Eastern Cooperative Oncology G Karnofsky performance status s TNM cl Guidelines 1. Classification and risk stratification Prognosis: recognize that high histological grade, perineural invasion, and lymphovascular invasion are the strongest predictors of metastasis of penile cancer. B 2. Diagnostic investigations Physical examination: https://web.pathway.md/diseases/recWSdyk1Or51ve9Z 1/5 6/29/23, 11:02 PM Penile cancer Pathway Physical examination: Perform a physical examination and record morphology, extent, and invasion of penile structures. A Perform a physical examination of both groins and record the number, laterality, and characteristics of inguinal nodes. A Imaging for staging: As per EAU 2018 guidelines, obtain pelvic CT or positron emission tomography/CT for staging of palpable inguinal lymph nodes. A Show 2 more As per ESMO 2013 guidelines, consider obtaining 18F-FDG-positron emission tomography/CT for the detection of pelvic lymph node metastases and identification of more distant metastases in patients with inguinal node-positive penile cancer. C 3. Diagnostic procedures Biopsy and histopathology: As per EAU 2018 guidelines, assess for HPV status during the pathological evaluation of penile carcinoma specimens. A Show 4 more As per ESMO 2013 guidelines: Perform dynamic sentinel node biopsy in intermediate (T1G2) or high-risk ( T1G3) disease with nonpalpable inguinal lymph nodes (cN0). Recognize that early detection of lymph node metastases by dynamic sentinel node biopsy and subsequent resection in clinically node-negative T2-3 penile cancer improves survival compared with surveillance. B Consider performing percutaneous FNA cytology biopsy and/or histology for the diagnosis of lymph node metastases in patients with palpable nodes. Perform a repeat biopsy or node excision in the case of a negative biopsy and clinically suspicious nodes. C 4. Medical management Management of locoregional disease, stages Tis, Ta: As per EAU 2018 guidelines: Offer the following options in patients with stage Tis disease: topical treatment with 5-fluorouracil or imiquimod, with or without photodynamic control, for superficial lesions laser ablation with CO or Nd-YAG laser glans resurfacing. A Offer the following options in patients with stage Ta (G1) disease: wide local excision with circumcision, CO or Nd-YAG laser with circumcision laser ablation with CO or Nd-YAG laser glans resurfacing glansectomy with reconstruction https://web.pathway.md/diseases/recWSdyk1Or51ve9Z 2/5 6/29/23, 11:02 PM Penile cancer Pathway radiotherapy for lesions < 4 cm. A As per ESMO 2013 guidelines: Offer penile-preserving strategy in patients with superficial and glans-confined tumors. B Offer the following penile-preserving techniques in patients with stage Tis/Ta disease: B topical therapy, such as 5-fluorouracil 5% and imiquimod 5% cream B circumcision and wide local excision B laser therapy using CO or Nd-YAG laser B partial/total glans resurfacing. B Management of locoregional disease, stages T1-2: As per EAU 2018 guidelines: Offer the following options in patients with stage T1a (G2) disease: wide local excision with circumcision, CO or Nd-YAG laser with circumcision laser ablation with CO or Nd-YAG laser glans resurfacing glansectomy with reconstruction radiotherapy for lesions < 4 cm in diameter. A Offer the following options in patients with stages T1b (G3) and T2 disease: wide local excision plus reconstruction glansectomy with circumcision and reconstruction radiotherapy for lesions < 4 cm in diameter. A As per ESMO 2013 guidelines, offer the following penile-preserving techniques in patients with T1G1-2 disease: B wide local excision plus reconstructive surgery with a split-thickness or full-thickness skin graft B laser therapy B radiotherapy delivered as external beam radiation therapy or brachytherapy with an interstitial implant. B Show 6 more Management of locoregional disease, stage T3: As per EAU 2018 guidelines: Perform partial amputation with reconstruction or radiotherapy in patients with stage T3 disease with lesions < 4 cm in diameter. A Perform partial penectomy or total penectomy with perineal urethrostomy in patients with stage T3 disease with urethral invasion. A As per ESMO 2013 guidelines, perform circumcision followed by external beam radiation therapy with chemotherapy in patients with stage T4 disease. B Management of advanced/metastatic disease: As per EAU 2018 guidelines, offer neoadjuvant chemotherapy followed by surgery in responders or palliative radiotherapy in patients with T4 disease. B Show 2 more https://web.pathway.md/diseases/recWSdyk1Or51ve9Z 3/5 6/29/23, 11:02 PM Penile cancer Pathway As per ESMO 2013 guidelines: Consider offering paclitaxel in combination with carboplatin as an alternative regimen in patients ineligible for cisplatin therapy. C Perform circumcision followed by external beam radiation therapy with chemotherapy in patients with T3-4 or N+ disease. B Management of lymph nodes: As per EAU 2018 guidelines, offer surveillance in patients with stages Tis, Ta (G1), and T1 disease with no palpable inguinal nodes (cN0). A Show 6 more As per ESMO 2013 guidelines, offer surveillance in low-risk (Tis, Ta, T1G1) and intermediate- risk (T1G2) patients without lymphovascular invasion. B Show 9 more Management of recurrent disease: As per EAU 2018 guidelines, perform penis-sparing salvage surgery or partial amputation in patients with small recurrences. B Show 2 more As per ESMO 2013 guidelines, consider offering salvage penile-sparing options in patients with recurrences without invasion of the corpora cavernosa. C Show 2 more 5. Perioperative care Preoperative imaging: obtain a penile Doppler ultrasound or MRI with artificial erection in patients with intended organ-sparing surgery. B Perioperative chemotherapy: As per ESMO 2013 guidelines: Consider offering cisplatin combination regimens for cytoreductive neoadjuvant chemotherapy. C Consider offering 4 cycles of neoadjuvant paclitaxel in combination with cisplatin and ifosfamide chemotherapy in patients with bulky regional disease (any T, N2, or N3) in the absence of distant metastatic disease. C 6. Follow-up and surveillance Follow-up: As per EAU 2018 guidelines, perform regular physician-led or self-examination every 3 months in 1-2 years and every 6 months in subsequent 3-5 years for monitoring of the primary tumor in patients after penile-preserving treatment. Repeat biopsy after topical or laser treatment for penile intraepithelial neoplasia. A Show 4 more As per ESMO 2013 guidelines: https://web.pathway.md/diseases/recWSdyk1Or51ve9Z 4/5 6/29/23, 11:02 PM Penile cancer Pathway Advise continuing regular self-examinations and reporting any changes even after a 5-year follow-up. Arrange follow-up visits after penectomy at intervals of every 6 months in the first 2 years and every 12 months in the following 3 years. B Recognize that most regional recurrences occur within 2 years after inguinal lymph node dissection or dynamic sentinel node biopsy. Obtain meticulous follow-up with US-guided FNA cytology biopsy of the groin every 3 months in the first 2 years and every 6 months in the following 3 years in patients subjected to a 'wait-and-see' policy (groins not surgically staged) and patients with positive nodes. B Clinical findings Symptoms Past medical history Fatigue Balanitis Penile bleeding Condyloma acuminatum Penile deformity HPV infection Penile discharge Human immunodeficiency virus infection Penile odor Lichen sclerosus Penile pain Phimosis Penile ulcer Sexually transmitted diseases Weight loss Social history Past events Multiple sexual partners Penile trauma Tobacco use Genitourinary exam Lymphatic exam Penile mass Inguinal lymphadenopathy Penile nodule References 1. H Van Poppel, N A Watkin, S Osanto et al. Penile cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi115 24. Open 2. O.W. Hakenberg Chair), E. Comp rat, S. Minhas et al. EAU Guidelines on Penile Cancer. EAU. 2018 Mar. Open 3. Oscar R Brouwer, Maarten Albersen, Arie Parnham et al. European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update. Eur Urol. 2023 Mar 7;S0302 2838 23 02638 6. Open https://web.pathway.md/diseases/recWSdyk1Or51ve9Z 5/5