Editing EAU & ASCO: Penile Cancer 2023 (section)

===== Clinical N3 Disease (fixed inguinal nodal pass or pelvic lymphadenopathy) =====
* '''Neoadjuvant chemotherapy (NAC) using a cisplatin- and taxane-based combination should be offered to chemotherapy-fit patients with pelvic lymph node involvement or those with extensive inguinal involvement (cN3), in preference to up front surgery.'''
** Bulky inguinal LN enlargement indicates extensive lymphatic metastatic disease for which few patients will benefit from surgery alone.
** Surgery as the initial treatment in patients with a fixed inguinal mass or clinically evident pelvic adenopathy (cN3) at presentation or recurrence is discouraged in routine management. 
*** Surgery alone will rarely cure patients with cN3 disease.
*** Even when technically feasible, upfront surgery often results in large skin/soft tissue defects, the need for myocutaneous flap reconstruction, prolonged hospital stays and is associated with high overall complication rates
** '''If responding to NAC and resection is feasible, offer surgery''' 
*** ≈50% with advanced (cN2–cN3) penile cancer respond to combination chemotherapy.
*** Responders that subsequently undergo consolidative inguinal/PLND have an OS chance of ≈50% at 5 years.
* If not candidate for conventional multi-agent chemotherapy, pre-operative chemo-radiation/radiation can be offered in an attempt to downsize tumours to improve resectability.
* Surgical resection 
** Timing
*** should proceed 5–8 weeks after completion of chemotherapy to provide time for haematologic recovery and other therapy related symptoms to improve.
** Technique
*** Inguinal LND in cN3 patients often requires resection of overlying skin to effectively remove a fixed bulky nodal mass
** Approach (1)
*** Open
**** Minimally-invasive techniques (i.e., robotic-, laparoscopic ILND) are considered inappropriate in cN3 inguinal metastases
** Pelvic lymph node dissection
*** Simultaneous PLND should be performed at the time of ILND if pelvic LN metastases were clinically evident at diagnosis.
*** Ipsilateral PLND should also be performed in a simultaneous (preferred) or delayed fashion in the setting of advanced bulky inguinal metastases without clinically evident pelvic metastases as well (i.e., prophylactic).