EAU & ASCO: Penile Cancer 2023: Difference between revisions

See [https://pubmed.ncbi.nlm.nih.gov/36906413/ Original Guidelines]

** pN1 Metastasis in one or two inguinal lymph nodes

** pN2 Metastasis in more than two unilateral inguinal nodes or bilateral inguinal lymph nodes

*'''Organ-sparing approaches are considered to be the primary treatment method for localised penile cancer due to superior functional and cosmetic outcomes compared to partial or total penectomy (amputation)'''

**'''Generally, penile-preserving surgery preserves erectile function, although glans sensation and orgasm can be affected'''

**'''Inform patients of the higher risk of local recurrence when using organ-sparing treatments compared to amputative surgery'''

*** <span style="color:#ff0000">'''Wide local excision (and circumcision)'''

**** '''Lesions located on the corona or glans, limited in size, may be treated with wide local excision which should include a margin of clinically normal-appearing skin around the tumour and surrounding erythema'''

*** <span style="color:#ff0000">'''Glansectomy (with or without reconstruction)'''

* Pre-operative MRI or US can assist in surgical planning

* In cT2 disease where there is doubt of corporeal or tunica albuginea invasion, rather than continuing the dissection over Buck’s fascia to perform glansectomy combined with distal corporectomy, dissection superficial to the tunica albuginea can be adopted after dividing the neurovascular bundle. In these instances, frozen sections of the corporeal tips and urethra may be helpful in assessing the radicality of the procedure peri-operatively.

* '''For cT3 patients with obvious involvement of the corpora cavernosa, partial amputation is standard.'''  

** Patients can be offered reconstructive options such as  

*** Urethral centralisation and/or  

*** Neo-glans formation with the use of a graft

** A total phallic reconstruction may be offered to patients undergoing total/subtotal amputation.

* '''Induction chemotherapy offers the ability to downstage disease and thereby enable surgical resection among responders, even among men with advanced penile cancer'''

** Several retrospective studies have evaluated combination regimens using paclitaxel or docetaxel with cisplatin and ifosfamide or 5-FU

* In case of not obtaining a response sufficient for resection, palliative chemo-radiotherapy is an option.

*Penile cancer metastasizes in a stepwise manner through the lymphatic system, initially to the inguinal nodes, then the pelvic nodes and finally to distant nodes

*Detecting lymphatic spread as early as possible is a crucial element in penile cancer management.

* Approximately 20-25% of cN0 patients may still harbour occult metastases, so additional staging is warranted

* Non-surgical staging

** Imaging

*** Not reliable to evaluate clinically node-negative patients

* Lymph node metastasis should preferably be histopathologically confirmed by image-guided biopsy (e.g., US or CT) before initiating treatment.

 

* Significant morbidity due to impaired lymph drainage from the legs and scrotum

** 21–55% of men will suffer a complication

** Most reported complications in recent series were

*** Wound infections (2–43%)

*** Skin necrosis (3–50%)

*** Lmphoedema (3.1–30%)

*** Lymphocele formation (1.8–26%)

*** Seroma (2.4–60%)

** Minimally-invasive approaches have been introduced

*** Although operative time is longer, LN yields can be similar to open ILND, length of hospital stay shorter in VEIL/RAVEIL and wound complications lower, though lymphocele and readmission rates were equivalent

===== cN1–N2 disease: radical inguinal lymph node dissection =====

* Open radical ILND is the standard for cN1–2 disease

* Offer neoadjuvant chemotherapy as an alternative approach to upfront surgery to selected patients with bulky mobile inguinal nodes or bilateral disease (cN2) who are candidates for cisplatin and taxane-based chemotherapy

* Complete surgical inguinal and pelvic nodal management within three months of diagnosis (unless the patient has undergone prior neoadjuvant chemotherapy).

* Delay in nodal management of more than three to six months may affect disease-free survival.

* Indications

**Three or more inguinal nodes are involved on one side on pathological examination

**Extranodal extension is reported on pathological examination

===== Clinical N3 Disease =====

* Offer neoadjuvant chemotherapy (NAC) using a cisplatin- and taxane-based combination to chemotherapy-fit patients with pelvic lymph node involvement or those with extensive inguinal involvement (cN3), in preference to up front surgery.

* Offer surgery to patients responding to NAC in whom resection is feasible.

** About half of the patients with advanced (cN2–cN3) penile cancer respond to combination chemotherapy. Responders that subsequently undergo consolidative inguinal/PLND have an OS chance of about 50% at 5 years.

* Among cN3 patients who are not candidates for conventional multi-agent chemotherapy, pre-operative chemo-radiation/radiation can be offered in an attempt to downsize tumours to improve resectability.

* Surgical resection should proceed 5–8 weeks after completion of chemotherapy to provide time for haematologic recovery and other therapy related symptoms to improve.

** Inguinal LND in cN3 patients often requires resection of overlying skin to effectively remove a fixed bulky nodal mass

* 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).

==== Systemic therapy ====

* Have a balanced discussion of risks and benefits of adjuvant chemotherapy with high-risk patients with surgically resected disease, in particular with those with pathological pelvic LN involvement (pN3)

* Offer adjuvant radiotherapy (with or without chemo sensitisation) to patients with pN2/N3 disease, including those who received prior neoadjuvant chemotherapy.

* Offer definitive radiotherapy (with or without chemo sensitisation) to patients unwilling or unable to undergo surgery.

* Offer radiotherapy (with or without chemo sensitisation) to cN3 patients who are not candidates for multi-agent chemotherapy.

*'''Prognostic factors'''

**'''Presence and extent of nodal metastases'''

***'''Most important prognostic factor for survival'''

***'''Extra-capsular extension in even one single LN carries a poor prognosis and is denoted as pN3'''

**'''Depth of invasion'''

**'''Grade in the primary tumour'''

**'''Pathological subtype'''

**'''Peri-neural invasion'''

**'''Lymphovascular invasion'''

* Local or regional nodal recurrences usually occur within two to three years of primary treatment

* After local treatment with negative inguinal nodes, follow-up should include physical examination of the penis and groins for local and/or regional recurrence. Additional imaging has no proven benefit

* Follow-up also depends on the primary treatment modality. Histology from the glans should be obtained to confirm disease-free status following laser ablation or topical chemotherapy

* Local recurrence is easily detected by physical examination, by the patient himself or his physician.

* Men should be assessed for genital and lower limb lymphoedema at each outpatient clinic appointment, advised about good skin care, compression, exercise, massage, and elevation when resting as the mainstay of treatment. Following nodal surgery, ideally, they would be referred to specialist lymphoedema services for assessment and management before any significant lymphoedema occurs.

*** For lower limb compression adjustable Velcro garments also exist.  

*** Good skin care is critical to prevent infection that can damage remaining lymphatic channels.

*** Prophylactic antibiotics should be used following any episode of cellulitis, with penicillin V, erythromycin or clindamycin recommended, except in genital lymphoedema where prophylactic trimethoprim can be used