Penile Cancer: Squamous Penile Cancer: Difference between revisions

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~~== Benign Tumours ==~~

'''See [[EAU & ASCO: Penile Cancer 2023|EAU & ASCO 2023 Penile Cancer 2023 Guideline Notes]]'''

~~=== Pearly penile papules ===~~

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

* '''~~Also known as papillomas~~'''

* '''Normal and generally found on the glans penis or corona'''

* Insert figure

~~=== Zoon balanitis ===~~

== Epidemiology ==

* '''Also called plasma cell balanitis''' and balanitis plasmacellularis

* '''Occurs in uncircumcised men from the 3rd decade onward'''

* '''Appearance: smooth, moist, erythematous, well-circumscribed plaques on the glans penis; shallow erosions are often present and lesions can be quite large (up to 2cm); difficult to distinguish from carcinoma in situ'''

** See Figure

* '''Pathology:'''

** Angiofibromas, similar to the lesions seen on the face in tuberous sclerosis

** '''Plasma cell infiltrate'''

* '''Diagnosis and evaluation: biopsy'''

** '''Malignancy and extra-mammary Paget’s disease must be excluded'''

* '''Management'''

** '''Circumcision'''

*** Curative in the majority of cases

*** Prevents against development of the disease

*** '''For patients wanting to avoid circumcision, topical corticosteroids may provide symptomatic relief'''; topical calcineurin inhibitors (tacrolimus or pimecrolimus) and laser therapy may also play a role

~~== Premalignant cutaneous lesions ==~~

* '''Classified as HPV-related vs. non-HPV related§'''

** '''HPV related (3): bowenoid papulosis, verrucous carcinoma, CIS'''

**# '''Bowenoid papulosis'''

**#* Appearance: multiple reddish-brown verrucous papules on the penile skin; occurs on the shaft of young men in most cases

**#** See Figure

**#* '''Histologically similar to low-grade carcinoma in situ [Bowen’s disease]'''

**#* '''HPV 16 has been suspected as a cause'''

**#* '''Progression rate to invasive cancer: 1%'''

**#* Diagnosis: biopsy (gold standard)

**#* Management: options include excision, electrocautery, cryotherapy, laser, or 5-fluorouracil topical therapy

**# '''Verrucous carcinoma (also known as classic Buschke-Löwenstein Tumor and giant condyloma)'''

**#* '''DNA from HPV types 6 and 11 has been identified in these tumors'''

**#* '''Progression rate to invasive cancer: 30%'''

**#** '''Exhibits progressive local growth but does not metastasize'''

**#** Results in invasion and destruction of adjacent tissues by compression

**#*** Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue.

**#* '''Management: often requires surgical excision for definitive treatment; radiation is ineffective'''

**#* INSERT FIGURE

**# '''CIS'''

**#* '''Erythroplasia of Queyrat'''

**#** '''CIS of the glans or foreskin/span>'''

**#** '''Progression rate to invasive cancer: 30%'''

**#* '''Bowen’s disease'''

**#** '''CIS the penile shaft or the remainder of the genitalia or perineal region/span>'''

**#** '''Progression rate to invasive cancer: 5%'''

**#** See Figure

**#* Metastasis extremely rare

**#* Not associated with visceral malignancies

** '''Non-HPV related (5):'''

**# '''Penile Kaposi sarcoma'''

**#* '''Often associated with herpes-virus 8'''

**#* '''Should prompt an investigation into whether patient is also infected with HIV or otherwise immunosuppressed'''

**#* '''Appears as a raised, painful, bleeding papule or ulcer with bluish discolouration'''

**#** See Figure

**#* Categories of Kaposi sarcoma (4):

**#*# Classic: occurs in patients without known immunodeficiency and typically has an indolent course

**#*# Immunosuppressive treatment-related: occurs in patients undergoing immunosuppression for organ transplantation or other reasons

**#*# African Kaposi sarcoma: occurs in young men and can be indolent or aggressive

**#*# Epidemic or HIV-related: occurs in patients with AIDS

**#** '''The classic and immunosuppressive forms of the disease are considered non-epidemic'''

**#*** '''Non-epidemic Kaposi sarcoma limited to penile involvement should be aggressively treated''' because it is rarely associated with diffuse organ involvement

**#* Management

**#** The first step in treatment of Kaposi's sarcoma in patients with HIV is to initiate HAART or to optimize the HAART regimen, which generally results in remission of Kaposi's sarcoma.

**#** Local treatment can include laser therapy, cryotherapy, surgical excision, application of topical retinoids.

**#** Disseminated or visceral Kaposi's sarcoma is treated with combination chemotherapy.

**# '''Penile cutaneous horn'''

**#* Rare

**#* Usually develops over a pre-existing skin lesion (wart, nevus, traumatic abrasion, or malignant neoplasm)

**#* Characterized by overgrowth and cornification of the epithelium, which forms a solid protuberance

**#** See Figure

**#* '''May recur and may demonstrate malignant change on subsequent biopsy, even when initial histological appearance is benign. As a result, careful histological evaluation of the base and close follow-up of the excision site are essential'''

**# '''Leucoplakia'''

**# '''Lichen sclerosis''' (see Penis and Urethra Surgery Chapter Notes)

**# '''Pseudoepitheliomatous micaceous and keratotic balanitis'''

~~== Squamous Cell Carcinoma of the Penis ==~~

* Accounts for > 95% of penile malignancies

=== Epidemiology ===

* Invasive Squamous Cell Carcinoma of the Penis

** Abrupt increase of incidence in the 6th decade of life

** Accounts for > 95% of penile malignancies

**Abrupt increase of incidence in the 6th decade of life

=== Risk factors ===

== Risk factors ==

# '''Lack of circumcision'''

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#* PUVA is a combination treatment which consists of Psoralens (P) and then exposing the skin to UVA (long wave ultraviolet radiation)

=== TNM Staging AJCC 8th edition ~~===~~

== TNM Staging ==

* AJCC 8th edition

==== Primary tumour (T) ====

=== Primary tumour (T) ===

* '''TX: Primary tumour cannot be assessed'''

* '''T0: No evidence of primary tumour'''

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* '''T4: invades other adjacent structures'''

==== Lymph nodes (N) ====

=== Lymph nodes (N) ===

* '''Clinical'''

** cNX: Regional nodes cannot be assessed

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*** A lymph node > 4 cm is often associated with extranodal extension of cancer.

==== Distant metastasis (M) ====

=== Distant metastasis (M) ===

* M0: No distant metastasis (no pathologic M0; use clinical M to complete staging group)

* M1: Distant metastasis: lymph node metastasis outside the true pelvis, or to visceral or bone sites

=== Natural history ===

== Natural history ==

* '''Tumour architecture'''

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* Death occurs in the majority of untreated patients within 2 years

=== Diagnosis and Evaluation ===

== Diagnosis and Evaluation ==

==== UrologySchool.com Summary ====

=== UrologySchool.com Summary ===

* '''History and Physical exam (including exam of inguinal nodes)'''

* '''Laboratory (1): serum calcium'''

* '''Laboratory (1): serum calcium, HPV status'''

* '''Imaging (2):'''

** '''Primary tumour'''

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* '''Other (1): biopsy'''

==== History and Physical Exam ====

=== History and Physical Exam ===

* '''History'''

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**** '''EAU Guidelines: Palpably enlarged lymph nodes are highly indicative of lymph node metastases. Physical examination should note the number of palpable nodes on each side and whether these are fixed or mobile. Additional imaging does not alter management and is not required'''

==== Laboratory ====

=== Laboratory ===

* '''Serum calcium'''

** '''Hypercalcemia may occur without detectable osseous metastases from elevated PTH''' and related substances produced by tumour

*'''HPV status'''

**'''Mandatory to determine HPV status when a patient is diagnosed with penile cancer[https://pubmed.ncbi.nlm.nih.gov/36906413/]'''

==== Imaging ====

=== Imaging ===

===== Primary tumour =====

==== Primary tumour ====

* '''For small-volume glanular lesions, imaging studies are not needed'''

* '''For larger lesions/lesions suspicious for invasion, US can provide information about infiltration of the corpora'''

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*** '''CT has poor soft-tissue resolution and is not useful for imaging the extent of the primary tumour'''

===== Metastases =====

==== Metastases ====

* '''Regional'''

** '''Physical exam of the inguinal region remains the clinical gold standard for evaluating the presence of metastasis in the non-obese patients'''

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**'''CT/PET scan'''

==== Other ====

=== Other ===

* '''Biopsy'''

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**# '''Vascular invasion'''

==== Differential diagnosis ====

=== Differential diagnosis ===

# Condyloma acuminatum (HPV warts)

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# Tuberculosis

=== Management ===

== Management ==

==== CIS ====

=== CIS ===

* '''Non-surgical'''

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* '''Moh's surgery'''

==== Favourable histologic features (stage Ta, T1; grade 1 and 2) ====

=== Favourable histologic features (stage Ta, T1; grade 1 and 2) ===

* '''Organ-sparing or glans-sparing surgical procedures'''

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***'''Because recurrence rates are higher with organ-preserving strategies, compliance with follow-up is also a consideration in recommending organ preservation versus amputation'''

==== Indications for partial or total penectomy (3): ====

=== Penectomy ===

==== Indications for partial or total penectomy (3):====

#'''High grade (grade ≥ 3) lesions'''

#'''[stage ≥ T2]; deep invasion into the glans urethra or corpora cavernosa'''

#'''Tumours >4cm'''

==== Treatment of ~~primary penile tumour summary =~~===

=== Treatment of Primary Penile Tumour Summary ===

* Tis (glans): Laser therapy, glans resurfacing; alternative: topical therapy

* Ta, Tis (foreskin, shaft skin): Surgical excision to achieve negative margin; alternatives: laser therapy, topical therapy (Tis only)

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* Radiotherapy: Select patients with T1-T2 tumors involving glans, coronal sulcus <4 cm

==== Treatment of ~~inguinal nodes =~~===

=== Treatment of Inguinal Nodes ===

* '''Lymph node involvement is most important prognostic factor for survival'''

** 5-year survival: lymph node involvement vs. without: 73% vs. 60% (range 0-86% depending on extent of lymph node involvement)

* '''Clinically negative groins'''

** '''≈20% of patients with clinically nonpalpable inguinal nodes harbor occult metastases'''

** '''Patients with stage ≥pT2 have high risk of metastasis, patients with pTis, pTa, pT1, grade 1 tumours have low risk of metastasis'''

*** '''Immediate resection of clinically occult lymph node metastases is associated with improved survival when compared with delayed resection of involved nodes at the time of clinical detection'''

** '''Patients with high-risk disease (high-grade or ≥pT2) should undergo lymph node staging with either bilateral modified inguinal lymphadenectomy or dynamic sentinel node biopsy'''

*** '''Dynamic Sentinel Node Biopsy''' (DNSB)

**** Sentinel lymph node biopsy is the technique to remove nodes that are first affected by the spread of metastatic disease.

***** Objective is to reduce the false-negative rate of groin dissection

***** The theory is that certain cancers typically do not spread to other lymph nodes without the necessary and stepwise involvement of the sentinel node first.

***** The concept of orderly lymphatic progression of metastatic cells from the primary tumor to the sentinel node seems to be likely with regard to squamous cell carcinoma of the penis.

**** Techniques reported to increase the accuracy of DNSB include:

****# Preoperative inguinal US with needle biopsy of any suspicious nodes

****# Routine inguinal exploration even in the absence of radiotracer visualization

****# Intraoperative palpation of the wound for abnormal nodes

****# Extended pathologic analysis of any excised lymph nodes

**** '''Procedure'''

***** Inguinal ultrasound and fine-needle aspiration (FNA) cytology of suspect lymph nodes has been added as a preliminary step before lymphoscintigraphy. Patients with abnormal nodes on ultrasound undergo FNA, and only patients with negative FNA findings proceed to scintigraphy and DSNB.

****** Patients with positive FNA findings undergo IFLND.

***** DNSB involves preoperative lymphoscintigraphy using technetium-99m nanocolloid, preoperative patent blue dye injection, and intraoperative guidance with a gamma ray detection probe to visualize the individual drainage pattern and accurately identify the sentinel node

***** [Further details in Campbell’s]

***** Dedicated experience is needed to gain optimal results

****** Should be performed with the goal of a false-negative rate at ≤5%

**** '''Follow-up'''

***** '''Strict follow-up is necessary to identify recurrences that can be managed surgically and potentially salvaged.'''

***** '''It is important to stress that DSNB remains a diagnostic procedure, allowing some men to avoid a therapeutic IFLND.'''

****** '''Those with a positive DSNB should proceed to a full therapeutic lymphadenectomy. It is not appropriate for palpable lymphadenopathy and applies only to clinically negative nodes'''.

****** '''In patients with palpable lymphadenopathy'''

*** '''Inguinal staging procedure'''

**** '''Begins with a superficial node dissection which involves removal of nodes superficial to fascia lata.'''

***** In patients with no evidence of palpable adenopathy who are selected to undergo inguinal procedures by virtue of adverse prognostic factors within the primary tumor, the goal is to define whether metastases exist with minimal morbidity. The gold-standard for detecting microscopic metastases is the superficial inguinal node dissection

**** '''Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.'''

***** '''Series have shown that in patients with negative superficial nodes, nodes deep to the fascia were always negative'''

***** Given morbidity of pelvic lymph node dissection, this can be spared in select patients with limited inguinal metastases

**** '''The superficial lymph node dissection should be bilateral'''

***** '''Lymph node dissection does not need to be bilateral if adenopathy is unilateral at recurrence (after treating primary tumour)'''

* '''Palpable adenopathy'''

** '''Associated with metastasis in 43% of cases, secondary to inflammation in the remainder'''; can consider fine-needle aspiration to differentiate

** '''Lymphadenectomy can be curative''' due to the prolonged locoregional phase before distant dissemination

** '''Inguinal lymphadenectomy is still recommended'''

*** '''The superficial lymph node dissection should be bilateral even if adenopathy is unilateral at presentation'''

*** '''Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.'''

** '''Exception is verrucous carcinoma, also known as a Buschke-Lowenstein tumor'''

*** Unlike penile squamous cell carcinoma, verrucous carcinoma of the penis has a very low likelihood of metastasis.

*** Palpable adenopathy in the context of verrucous carcinoma is very likely to be reactive and should be initially observed. Biopsy should be reserved unless the node remains persistently enlarged or grows over time.

*** '''Lymphadenectomy in the context of verrucous carcinoma should be reserved for cases of biopsy-proven metastases.'''

* '''Fixed inguinal lymph nodes (cN3)'''

** '''Neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders'''

* '''2018 EAU Penile Cancer Guidelines: Summary of treatment strategies for nodal metastases'''

==== Clinically negative groins ====

* '''≈20% of patients with clinically nonpalpable inguinal nodes harbor occult metastases'''

**Cross-sectional imaging studies such as CT and magnetic resonance imaging (MRI) are unable to accurately detect these cases and are only largely used to assess for the presence of pelvic lymph node involvement

**'''Immediate resection of clinically occult lymph node metastases is associated with improved survival when compared with delayed resection of involved nodes at the time of clinical detection'''

* '''Surgical staging'''

**'''Indications'''

***'''Recommended (1):'''

****'''High-risk tumor (≥pT1b)'''

***'''Optional (1):'''

****'''T1a G2 disease'''

*****'''Surveillance is an alternative to surgical staging with patients willing to comply with strict follow-up'''

**'''Options (2)'''

**#'''Dynamic sentinel node biopsy (DNSB) (preferred)[https://pubmed.ncbi.nlm.nih.gov/36906413/]'''

**#* Sentinel lymph node biopsy is the technique to remove nodes that are first affected by the spread of metastatic disease.

**#**Based on the assumption that penile cancer cells will initially spread unilaterally or bilaterally to a single inguinal lymph node before disseminating to adjoining lymph nodes and that this sentinel lymph node can have a variable position among individuals

**#***The theory is that certain cancers typically do not spread to other lymph nodes without the necessary and stepwise involvement of the sentinel node first.

**#***The concept of orderly lymphatic progression of metastatic cells from the primary tumor to the sentinel node seems to be likely with regard to squamous cell carcinoma of the penis.

**#*Technique

**#**Inguinal ultrasound and fine-needle aspiration (FNA) cytology of suspect lymph nodes has been added as a preliminary step before lymphoscintigraphy. Patients with abnormal nodes on ultrasound undergo FNA, and only patients with negative FNA findings proceed to scintigraphy and DSNB.

**#*** Patients with positive FNA findings undergo inguinal lymph node dissection.

**#**DNSB involves preoperative lymphoscintigraphy using technetium-99m nanocolloid, preoperative patent blue dye injection, and intraoperative guidance with a gamma ray detection probe to visualize the individual drainage pattern and accurately identify the sentinel node, which is subsequently resected

**#*'''Advantages'''

**#**'''Significantly less morbid than modified inguinal lymph node dissection or a standard lymphadenectomy'''

**#***Can serve as an intermediary between noninvasive imaging modalities and surgical resection when identifying those patients with clinically negative groins who would benefit from inguinal lymphadenectomy

**#*'''Disadvantages'''

**#** '''Widespread use of DSNB remains limited and generally restricted to high-volume centers'''

**#***Dedicated experience is needed to gain optimal results

**#**** Should be performed with the goal of a false-negative rate at ≤5%

**#****Methods to increase the accuracy of DNSB (4):

**#***# Preoperative inguinal US with needle biopsy of any suspicious nodes

**#***# Routine inguinal exploration even in the absence of radiotracer visualization

**#***# Intraoperative palpation of the wound for abnormal nodes

**#***# Extended pathologic analysis of any excised lymph nodes

**#* '''Follow-up'''

**#** '''Strict follow-up is necessary to identify recurrences that can be managed surgically and potentially salvaged.'''

**#** '''It is important to stress that DSNB remains a diagnostic procedure, allowing some men to avoid a therapeutic IFLND.'''

**#*** '''Those with a positive DSNB should proceed to a full therapeutic lymphadenectomy. It is not appropriate for palpable lymphadenopathy and applies only to clinically negative nodes'''.

**#*** '''In patients with palpable lymphadenopathy'''

**#'''Bilateral inguinal lymph node dissection (ILND)'''

**#*'''Lymphatic spread of penile carcinoma can be unilateral or bilateral to the inguinal lymph nodes'''

**#*Approaches (2):

**#**Open

**#**Video-endoscopic surgery

==== Palpable adenopathy ====

* '''Associated with metastasis in 43% of cases, secondary to inflammation in the remainder'''; can consider fine-needle aspiration to differentiate

* '''Lymphadenectomy can be curative''' due to the prolonged locoregional phase before distant dissemination

* '''Inguinal lymphadenectomy is still recommended'''

** '''The superficial lymph node dissection should be bilateral even if adenopathy is unilateral at presentation'''

** '''Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.'''

* '''Exception is verrucous carcinoma, also known as a Buschke-Lowenstein tumor'''

** Unlike penile squamous cell carcinoma, verrucous carcinoma of the penis has a very low likelihood of metastasis.

** Palpable adenopathy in the context of verrucous carcinoma is very likely to be reactive and should be initially observed. Biopsy should be reserved unless the node remains persistently enlarged or grows over time.

** '''Lymphadenectomy in the context of verrucous carcinoma should be reserved for cases of biopsy-proven metastases.'''

==== Fixed inguinal lymph nodes (cN3) ====

* '''Neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders'''

==== Lymph node involvement (pN+) ====

*'''Prognosis'''

**'''Pathologic criteria associated with improved long-term survival after attempted curative surgical resection of inguinal metastases include:'''

**# '''Unilateral involvement'''

**# '''Minimal nodal disease (≤2 involved nodes in most series (pN1))'''

**# '''No evidence of extra nodal extension of cancer (pN3)'''

**# '''Absence of pelvic nodal metastases (pN3)'''

**## '''i.e. pN1, and lack of features associated with pN2 and pN3'''

* '''No anatomic or lymphangiographic studies demonstrating direct lymphatic drainage to the pelvic lymph nodes from the penis, which is evidenced by the lack of metastatic spread to the pelvic lymph nodes from a primary penile tumor in the absence of metastatic spread to the inguinal lymph nodes[https://link.springer.com/book/10.1007/978-3-319-60858-7]'''

*'''Indications for pelvic lymph node dissection in patients undergoing inguinal lymph node dissection for curative intent (no pelvic adenopathy) (2):'''

*# '''≥2 positive inguinal lymph nodes'''

*# '''Extra-nodal extension is present'''

*## '''PLND in this setting serves as staging tool to identify patients who should be considered for adjunctive therapy'''

*## '''PLND includes the distal common iliac, external iliac, and obturator groups of nodes.'''

==== Summary of treatment strategies for nodal metastases ====

{| class="wikitable"

|'''Lymph node status'''

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|'''Not recommended for nodal disease except as a palliative option'''

|}

'''2018 EAU Penile Cancer Guidelines'''

~~==== Lymph node involvement ====~~

=== Radiation ===

*'''Pathologic criteria associated with improved long-term survival after attempted curative surgical resection of inguinal metastases include:'''

*# '''Unilateral involvement'''

*# '''Minimal nodal disease (≤2 involved nodes in most series (pN1))'''

*# '''No evidence of extra nodal extension of cancer (pN3)'''

*# '''Absence of pelvic nodal metastases (pN3)'''

*## '''i.e. pN1, and lack of features associated with pN2 and pN3'''

* '''Indications for pelvic lymph node dissection in patients undergoing inguinal lymph node dissection for curative intent (no pelvic adenopathy) (2):'''

*# '''≥2 positive inguinal lymph nodes'''

*# '''Extra-nodal extension is present'''

*## '''PLND in this setting serves as staging tool to identify patients who should be considered for adjunctive therapy'''

*## '''PLND includes the distal common iliac, external iliac, and obturator groups of nodes.'''

==== Radiation ====

* '''An option for those with invasive SCC refusing surgical treatment'''

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* '''Palliative radiotherapy among patients with inoperable inguinal nodes may provide some benefit'''

==== Chemotherapy ====

=== Chemotherapy ===

* '''Treatment with a cisplatin-containing regimen in advanced metastatic penile cancer should be considered''' and this may facilitate curative resection. The optimal regimen has yet to be determined.

* Among patients whose tumour progresses through chemotherapy, surgery is not recommended

~~== Non-squamous penile malignant neoplasms ==~~

* '''Extremely rare'''

~~=== Basal cell carcinoma ===~~

* Frequently encountered on other sun-exposed cutaneous surfaces, it is '''rare on the penis'''

* Treatment is by local excision, which is virtually always curative

~~=== Melanoma ===~~

* Aggressive form of cancer but can be cured if diagnosed and treated with the appropriate surgical treatment at an early stage

** '''Surgery is the primary mode of treatment'''; radiation therapy and chemotherapy are of only adjunctive or palliative benefit

~~=== Sarcoma ===~~

* Prone to local recurrence; regional and distant metastases are rare.

* Superficial lesions can be treated with less radical procedures

~~=== Extramammary Paget Disease ===~~

* Appearance

** Erythematous, eczematoid, well-demarcated area

** Cannot be clinically distinguished from erythroplasia of Queyrat, Bowen disease, or carcinoma in situ of the penis

** See Figure

* Clinical presentation

** Local discomfort, pruritus, and occasionally a serosanguineous discharge involving the penis, the scrotum, or even the perianal area

* '''Behaves as a slow-growing intraepithelial adenocarcinoma'''

** With time the cells may become invasive with dermal tumor deposits metastasizing to regional lymph nodes via dermal lymphatics penoscrotal

* '''May be associated with other malignancies of the genitourinary tract, such as prostate, bladder, and renal malignancies and should be evaluated for their presence'''

* '''Management'''

** '''In most cases, only the skin and dermis must be resected with a gross margin of up to 3 cm'''. '''Positive margins may still occur, and frozen sections are recommended to guide the extent of resection.'''

*** Patients with a positive surgical margin are at a higher risk for recurrence, and additional resection is advised

** Local skin or scrotal flaps can be used to cover the defects.

** In a minority of cases the tumor may invade deeper structures, necessitating more extensive resection and reconstruction

** If inguinal adenopathy is present, radical node dissection is advised but prognosis is poor

~~=== Adenosquamous carcinoma ===~~

~~=== Lymphoreticular malignant neoplasm ===~~

~~=== Metastases ===~~

* Most often represent spread from a clinically obvious existing primary tumor.

* Prognosis is poor, and therapy should be directed toward the primary tumor site histology and local palliation

* '''Priapism is the most frequently encountered sign of metastatic involvement of the penis'''

~~'''Lymphomatous infiltration of the penis is most likely secondary to diffuse disease'''~~

== References ==

* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015

* Brouwer, Oscar R., et al. "European association of urology-american society of clinical oncology collaborative guideline on penile cancer: 2023 update." ''European urology'' (2023).

* [https://pubmed.ncbi.nlm.nih.gov/36906413/ Brouwer, Oscar R., et al. "European association of urology-american society of clinical oncology collaborative guideline on penile cancer: 2023 update." ''European urology'' (2023).]

@@ Line 1: / Line 1: @@
-== Benign Tumours ==
+'''See [[EAU & ASCO: Penile Cancer 2023|EAU & ASCO 2023 Penile Cancer 2023 Guideline Notes]]'''
-=== Pearly penile papules ===
+* '''See [https://pubmed.ncbi.nlm.nih.gov/36906413/ Original Guidelines]'''
-* '''Also known as papillomas'''
-* '''Normal and generally found on the glans penis or corona'''
-* Insert figure
-=== Zoon balanitis ===
+== Epidemiology ==
-* '''Also called plasma cell balanitis''' and balanitis plasmacellularis
-* '''Occurs in uncircumcised men from the 3rd decade onward'''
-* '''Appearance: smooth, moist, erythematous, well-circumscribed plaques on the glans penis; shallow erosions are often present and lesions can be quite large (up to 2cm); difficult to distinguish from carcinoma in situ'''
-** See Figure
-* '''Pathology:'''
-** Angiofibromas, similar to the lesions seen on the face in tuberous sclerosis
-** '''Plasma cell infiltrate'''
-* '''Diagnosis and evaluation: biopsy'''
-** '''Malignancy and extra-mammary Paget’s disease must be excluded'''
-* '''Management'''
-** '''Circumcision'''
-*** Curative in the majority of cases
-*** Prevents against development of the disease
-*** '''For patients wanting to avoid circumcision, topical corticosteroids may provide symptomatic relief'''; topical calcineurin inhibitors (tacrolimus or pimecrolimus) and laser therapy may also play a role
-== Premalignant cutaneous lesions ==
-* '''<span style="color:#ff0000">Classified as HPV-related vs. non-HPV related</span>§'''
-** '''<span style="color:#ff0000">HPV related (3): bowenoid papulosis, verrucous carcinoma, CIS</span>'''
-**# '''<span style="color:#ff0000">Bowenoid papulosis</span>'''
-**#* Appearance: multiple reddish-brown verrucous papules on the penile skin; occurs on the shaft of young men in most cases
-**#** See Figure
-**#* '''Histologically similar to low-grade carcinoma in situ [Bowen’s disease]'''
-**#* '''HPV 16 has been suspected as a cause'''
-**#* '''Progression rate to invasive cancer: 1%'''
-**#* Diagnosis: biopsy (gold standard)
-**#* Management: options include excision, electrocautery, cryotherapy, laser, or 5-fluorouracil topical therapy
-**# '''<span style="color:#ff0000">Verrucous carcinoma (also known as classic Buschke-Löwenstein Tumor and giant condyloma)</span>'''
-**#* '''DNA from HPV types 6 and 11 has been identified in these tumors'''
-**#* '''Progression rate to invasive cancer: 30%'''
-**#** '''Exhibits progressive local growth but does not metastasize'''
-**#** Results in invasion and destruction of adjacent tissues by compression
-**#*** Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue.
-**#* '''Management: often requires surgical excision for definitive treatment; radiation is ineffective'''
-**#* INSERT FIGURE
-**# '''<span style="color:#ff0000">CIS</span>'''
-**#* '''<span style="color:#ff0000">Erythroplasia of Queyrat</span>'''
-**#** '''<span style="color:#ff0000">CIS of the glans or foreskin/span>'''
-**#** '''Progression rate to invasive cancer: 30%'''
-**#* '''<span style="color:#ff0000">Bowen’s disease</span>'''
-**#** '''<span style="color:#ff0000">CIS the penile shaft or the remainder of the genitalia or perineal region/span>'''
-**#** '''Progression rate to invasive cancer: 5%'''
-**#** See Figure
-**#* Metastasis extremely rare
-**#* Not associated with visceral malignancies
-** '''<span style="color:#ff0000">Non-HPV related (5):</span>'''
-**# '''<span style="color:#ff0000">Penile Kaposi sarcoma</span>'''
-**#* '''<span style="color:#ff0000">Often associated with herpes-virus 8</span>'''
-**#* '''Should prompt an investigation into whether patient is also infected with HIV or otherwise immunosuppressed'''
-**#* '''Appears as a raised, painful, bleeding papule or ulcer with bluish discolouration'''
-**#** See Figure
-**#* Categories of Kaposi sarcoma (4):
-**#*# Classic: occurs in patients without known immunodeficiency and typically has an indolent course
-**#*# Immunosuppressive treatment-related: occurs in patients undergoing immunosuppression for organ transplantation or other reasons
-**#*# African Kaposi sarcoma: occurs in young men and can be indolent or aggressive
-**#*# Epidemic or HIV-related: occurs in patients with AIDS
-**#** '''The classic and immunosuppressive forms of the disease are considered non-epidemic'''
-**#*** '''Non-epidemic Kaposi sarcoma limited to penile involvement should be aggressively treated''' because it is rarely associated with diffuse organ involvement
-**#* Management
-**#** The first step in treatment of Kaposi's sarcoma in patients with HIV is to initiate HAART or to optimize the HAART regimen, which generally results in remission of Kaposi's sarcoma.
-**#** Local treatment can include laser therapy, cryotherapy, surgical excision, application of topical retinoids.
-**#** Disseminated or visceral Kaposi's sarcoma is treated with combination chemotherapy.
-**# '''<span style="color:#ff0000">Penile cutaneous horn</span>'''
-**#* Rare
-**#* Usually develops over a pre-existing skin lesion (wart, nevus, traumatic abrasion, or malignant neoplasm)
-**#* Characterized by overgrowth and cornification of the epithelium, which forms a solid protuberance
-**#** See Figure
-**#* '''May recur and may demonstrate malignant change on subsequent biopsy, even when initial histological appearance is benign. As a result, careful histological evaluation of the base and close follow-up of the excision site are essential'''
-**# '''<span style="color:#ff0000">Leucoplakia</span>'''
-**# '''<span style="color:#ff0000">Lichen sclerosis</span>''' (see Penis and Urethra Surgery Chapter Notes)
-**# '''<span style="color:#ff0000">Pseudoepitheliomatous micaceous and keratotic balanitis</span>'''
-== Squamous Cell Carcinoma of the Penis ==
-* Accounts for > 95% of penile malignancies
-=== Epidemiology ===
 * Invasive Squamous Cell Carcinoma of the Penis
-** Abrupt increase of incidence in the 6th decade of life
+** Accounts for > 95% of penile malignancies
+**Abrupt increase of incidence in the 6th decade of life
-=== Risk factors ===
+== Risk factors ==
 # '''<span style="color:#ff0000">Lack of circumcision</span>'''
@@ Line 109: / Line 28: @@
 #* PUVA is a combination treatment which consists of Psoralens (P) and then exposing the skin to UVA (long wave ultraviolet radiation)
-=== TNM Staging AJCC 8th edition ===
+== TNM Staging ==
+* AJCC 8th edition
-==== Primary tumour (T) ====
+=== Primary tumour (T) ===
 * '''TX: Primary tumour cannot be assessed'''
 * '''T0: No evidence of primary tumour'''
@@ Line 123: / Line 44: @@
 * '''<span style="color:#ff0000">T4: invades other adjacent structures</span>'''
-==== Lymph nodes (N) ====
+=== Lymph nodes (N) ===
 * '''Clinical'''
 ** cNX: Regional nodes cannot be assessed
@@ Line 138: / Line 59: @@
 *** A lymph node > 4 cm is often associated with extranodal extension of cancer.
-==== Distant metastasis (M) ====
+=== Distant metastasis (M) ===
 * M0: No distant metastasis (no pathologic M0; use clinical M to complete staging group)
 * M1: Distant metastasis: lymph node metastasis outside the true pelvis, or to visceral or bone sites
-=== Natural history ===
+== Natural history ==
 * '''Tumour architecture'''
@@ Line 166: / Line 87: @@
 * Death occurs in the majority of untreated patients within 2 years
-=== Diagnosis and Evaluation ===
+== Diagnosis and Evaluation ==
-==== UrologySchool.com Summary ====
+=== UrologySchool.com Summary ===
 * '''<span style="color:#ff0000">History and Physical exam (including exam of inguinal nodes)</span>'''
-* '''<span style="color:#ff0000">Laboratory (1): serum calcium</span>'''
+* '''<span style="color:#ff0000">Laboratory (1): serum calcium, HPV status</span>'''
 * '''<span style="color:#ff0000">Imaging (2):</span>'''
 ** '''<span style="color:#ff0000">Primary tumour</span>'''
@@ Line 179: / Line 100: @@
 * '''<span style="color:#ff0000">Other (1): biopsy</span>'''
-==== History and Physical Exam ====
+=== History and Physical Exam ===
 * '''History'''
@@ Line 194: / Line 115: @@
 **** '''EAU Guidelines: Palpably enlarged lymph nodes are highly indicative of lymph node metastases. Physical examination should note the number of palpable nodes on each side and whether these are fixed or mobile. Additional imaging does not alter management and is not required'''
-==== Laboratory ====
+=== Laboratory ===
 * '''<span style="color:#ff0000">Serum calcium'''
 ** '''<span style="color:#ff0000">Hypercalcemia may occur without detectable osseous metastases from elevated PTH''' and related substances produced by tumour
+*'''<span style="color:#ff0000">HPV status'''
+**'''Mandatory to determine HPV status when a patient is diagnosed with penile cancer[https://pubmed.ncbi.nlm.nih.gov/36906413/]'''
-==== Imaging ====
+=== Imaging ===
-===== Primary tumour =====
+==== Primary tumour ====
 * '''<span style="color:#ff0000">For small-volume glanular lesions, imaging studies are not needed'''
 * '''<span style="color:#ff0000">For larger lesions/lesions suspicious for invasion, US can provide information about infiltration of the corpora'''
@@ Line 208: / Line 131: @@
 *** '''CT has poor soft-tissue resolution and is not useful for imaging the extent of the primary tumour'''
-===== Metastases =====
+==== Metastases ====
 * '''<span style="color:#ff0000">Regional'''
 ** '''<span style="color:#ff0000">Physical exam of the inguinal region remains the clinical gold standard for evaluating the presence of metastasis in the non-obese patients'''
@@ Line 219: / Line 142: @@
 **'''CT/PET scan'''
-==== Other ====
+=== Other ===
 * '''<span style="color:#ff0000">Biopsy</span>'''
@@ Line 236: / Line 159: @@
 **# '''<span style="color:#ff0000">Vascular invasion</span>'''
-==== Differential diagnosis ====
+=== Differential diagnosis ===
 # Condyloma acuminatum (HPV warts)
@@ Line 244: / Line 167: @@
 # Tuberculosis
-=== Management ===
+== Management ==
-==== CIS ====
+=== CIS ===
 * '''<span style="color:#ff0000">Non-surgical</span>'''
@@ Line 267: / Line 190: @@
 * '''<span style="color:#ff0000">Moh's surgery</span>'''
-==== Favourable histologic features (stage Ta, T1; grade 1 and 2) ====
+=== Favourable histologic features (stage Ta, T1; grade 1 and 2) ===
 * '''<span style="color:#ff0000">Organ-sparing or glans-sparing surgical procedures</span>'''
@@ Line 287: / Line 210: @@
 ***'''Because recurrence rates are higher with organ-preserving strategies, compliance with follow-up is also a consideration in recommending organ preservation versus amputation'''
-==== Indications for partial or total penectomy (3): ====
+=== Penectomy ===
+==== Indications for partial or total penectomy (3):====
 #'''<span style="color:#ff0000">High grade (grade ≥ 3) lesions</span>'''
 #'''<span style="color:#ff0000">[stage ≥ T2]; deep invasion into the glans urethra or corpora cavernosa</span>'''
 #'''<span style="color:#ff0000">Tumours >4cm</span>'''
-==== Treatment of primary penile tumour summary ====
+=== Treatment of Primary Penile Tumour Summary ===
 * Tis (glans): Laser therapy, glans resurfacing; alternative: topical therapy
 * Ta, Tis (foreskin, shaft skin): Surgical excision to achieve negative margin; alternatives: laser therapy, topical therapy (Tis only)
@@ Line 304: / Line 228: @@
 * Radiotherapy: Select patients with T1-T2 tumors involving glans, coronal sulcus <4 cm
-==== Treatment of inguinal nodes ====
+=== Treatment of Inguinal Nodes ===
 * '''<span style="color:#ff0000">Lymph node involvement is most important prognostic factor for survival</span>'''
 ** 5-year survival: lymph node involvement vs. without: 73% vs. 60% (range 0-86% depending on extent of lymph node involvement)
-* '''<span style="color:#ff0000">Clinically negative groins</span>'''
-** '''<span style="color:#ff0000">≈20% of patients with clinically nonpalpable inguinal nodes harbor occult metastases</span>'''
-** '''Patients with stage ≥pT2 have high risk of metastasis, patients with pTis, pTa, pT1, grade 1 tumours have low risk of metastasis'''
-*** '''Immediate resection of clinically occult lymph node metastases is associated with improved survival when compared with delayed resection of involved nodes at the time of clinical detection'''
-** '''<span style="color:#ff0000">Patients with high-risk disease (high-grade or ≥pT2) should undergo lymph node staging with either bilateral modified inguinal lymphadenectomy or dynamic sentinel node biopsy</span>'''
-*** '''Dynamic Sentinel Node Biopsy''' (DNSB)
-**** Sentinel lymph node biopsy is the technique to remove nodes that are first affected by the spread of metastatic disease.
-***** Objective is to reduce the false-negative rate of groin dissection
-***** The theory is that certain cancers typically do not spread to other lymph nodes without the necessary and stepwise involvement of the sentinel node first.
-***** The concept of orderly lymphatic progression of metastatic cells from the primary tumor to the sentinel node seems to be likely with regard to squamous cell carcinoma of the penis.
-**** Techniques reported to increase the accuracy of DNSB include:
-****# Preoperative inguinal US with needle biopsy of any suspicious nodes
-****# Routine inguinal exploration even in the absence of radiotracer visualization
-****# Intraoperative palpation of the wound for abnormal nodes
-****# Extended pathologic analysis of any excised lymph nodes
-**** '''Procedure'''
-***** Inguinal ultrasound and fine-needle aspiration (FNA) cytology of suspect lymph nodes has been added as a preliminary step before lymphoscintigraphy. Patients with abnormal nodes on ultrasound undergo FNA, and only patients with negative FNA findings proceed to scintigraphy and DSNB.
-****** Patients with positive FNA findings undergo IFLND.
-***** DNSB involves preoperative lymphoscintigraphy using technetium-99m nanocolloid, preoperative patent blue dye injection, and intraoperative guidance with a gamma ray detection probe to visualize the individual drainage pattern and accurately identify the sentinel node
-***** [Further details in Campbell’s]
-***** Dedicated experience is needed to gain optimal results
-****** Should be performed with the goal of a false-negative rate at ≤5%
-**** '''Follow-up'''
-***** '''Strict follow-up is necessary to identify recurrences that can be managed surgically and potentially salvaged.'''
-***** '''It is important to stress that DSNB remains a diagnostic procedure, allowing some men to avoid a therapeutic IFLND.'''
-****** '''Those with a positive DSNB should proceed to a full therapeutic lymphadenectomy. It is not appropriate for palpable lymphadenopathy and applies only to clinically negative nodes'''.
-****** '''In patients with palpable lymphadenopathy'''
-*** '''Inguinal staging procedure'''
-**** '''Begins with a superficial node dissection which involves removal of nodes superficial to fascia lata.'''
-***** In patients with no evidence of palpable adenopathy who are selected to undergo inguinal procedures by virtue of adverse prognostic factors within the primary tumor, the goal is to define whether metastases exist with minimal morbidity. The gold-standard for detecting microscopic metastases is the superficial inguinal node dissection
-**** '''Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.'''
-***** '''Series have shown that in patients with negative superficial nodes, nodes deep to the fascia were always negative'''
-***** Given morbidity of pelvic lymph node dissection, this can be spared in select patients with limited inguinal metastases
-**** '''The superficial lymph node dissection should be bilateral'''
-***** '''Lymph node dissection does not need to be bilateral if adenopathy is unilateral at recurrence (after treating primary tumour)'''
-* '''<span style="color:#ff0000">Palpable adenopathy</span>'''
-** '''Associated with metastasis in 43% of cases, secondary to inflammation in the remainder'''; can consider fine-needle aspiration to differentiate
-** '''Lymphadenectomy can be curative''' due to the prolonged locoregional phase before distant dissemination
-** '''Inguinal lymphadenectomy is still recommended'''
-*** '''<span style="color:#ff0000">The superficial lymph node dissection should be bilateral even if adenopathy is unilateral at presentation</span>'''
-*** '''<span style="color:#ff0000">Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.</span>'''
-** '''Exception is verrucous carcinoma, also known as a Buschke-Lowenstein tumor'''
-*** Unlike penile squamous cell carcinoma, verrucous carcinoma of the penis has a very low likelihood of metastasis.
-*** Palpable adenopathy in the context of verrucous carcinoma is very likely to be reactive and should be initially observed. Biopsy should be reserved unless the node remains persistently enlarged or grows over time.
-*** '''Lymphadenectomy in the context of verrucous carcinoma should be reserved for cases of biopsy-proven metastases.'''
-* '''<span style="color:#ff0000">Fixed inguinal lymph nodes (cN3)</span>'''
-** '''<span style="color:#ff0000">Neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders</span>'''
-* '''2018 EAU Penile Cancer Guidelines: Summary of treatment strategies for nodal metastases'''
+==== <span style="color:#ff0000">Clinically negative groins</span> ====
+* '''<span style="color:#ff0000">≈20% of patients with clinically nonpalpable inguinal nodes harbor occult metastases</span>'''
+**Cross-sectional imaging studies such as CT and magnetic resonance imaging (MRI) are unable to accurately detect these cases and are only largely used to assess for the presence of pelvic lymph node involvement
+**'''Immediate resection of clinically occult lymph node metastases is associated with improved survival when compared with delayed resection of involved nodes at the time of clinical detection'''
+* '''<span style="color:#ff0000">Surgical staging</span>'''
+**'''<span style="color:#ff0000">Indications</span>'''
+***'''<span style="color:#ff0000">Recommended (1):</span>'''
+****'''<span style="color:#ff0000">High-risk tumor (≥pT1b)</span>'''
+***'''<span style="color:#ff0000">Optional (1):</span>'''
+****'''<span style="color:#ff0000">T1a G2 disease</span>'''
+*****'''<span style="color:#ff0000">Surveillance is an alternative to surgical staging with patients willing to comply with strict follow-up</span>'''
+**'''<span style="color:#ff0000">Options (2)</span>'''
+**#'''<span style="color:#ff0000">Dynamic sentinel node biopsy (DNSB) (preferred)[https://pubmed.ncbi.nlm.nih.gov/36906413/]</span>'''
+**#* Sentinel lymph node biopsy is the technique to remove nodes that are first affected by the spread of metastatic disease.
+**#**Based on the assumption that penile cancer cells will initially spread unilaterally or bilaterally to a single inguinal lymph node before disseminating to adjoining lymph nodes and that this sentinel lymph node can have a variable position among individuals
+**#***The theory is that certain cancers typically do not spread to other lymph nodes without the necessary and stepwise involvement of the sentinel node first.
+**#***The concept of orderly lymphatic progression of metastatic cells from the primary tumor to the sentinel node seems to be likely with regard to squamous cell carcinoma of the penis.
+**#*Technique
+**#**Inguinal ultrasound and fine-needle aspiration (FNA) cytology of suspect lymph nodes has been added as a preliminary step before lymphoscintigraphy. Patients with abnormal nodes on ultrasound undergo FNA, and only patients with negative FNA findings proceed to scintigraphy and DSNB.
+**#*** Patients with positive FNA findings undergo inguinal lymph node dissection.
+**#**DNSB involves preoperative lymphoscintigraphy using technetium-99m nanocolloid, preoperative patent blue dye injection, and intraoperative guidance with a gamma ray detection probe to visualize the individual drainage pattern and accurately identify the sentinel node, which is subsequently resected
+**#*'''Advantages'''
+**#**'''Significantly less morbid than modified inguinal lymph node dissection or a standard lymphadenectomy'''
+**#***Can serve as an intermediary between noninvasive imaging modalities and surgical resection when identifying those patients with clinically negative groins who would benefit from inguinal lymphadenectomy
+**#*'''Disadvantages'''
+**#** '''Widespread use of DSNB remains limited and generally restricted to high-volume centers'''
+**#***Dedicated experience is needed to gain optimal results
+**#**** Should be performed with the goal of a false-negative rate at ≤5%
+**#****Methods to increase the accuracy of DNSB (4):
+**#***# Preoperative inguinal US with needle biopsy of any suspicious nodes
+**#***# Routine inguinal exploration even in the absence of radiotracer visualization
+**#***# Intraoperative palpation of the wound for abnormal nodes
+**#***# Extended pathologic analysis of any excised lymph nodes
+**#* '''Follow-up'''
+**#** '''Strict follow-up is necessary to identify recurrences that can be managed surgically and potentially salvaged.'''
+**#** '''It is important to stress that DSNB remains a diagnostic procedure, allowing some men to avoid a therapeutic IFLND.'''
+**#*** '''Those with a positive DSNB should proceed to a full therapeutic lymphadenectomy. It is not appropriate for palpable lymphadenopathy and applies only to clinically negative nodes'''.
+**#*** '''In patients with palpable lymphadenopathy'''
+**#'''<span style="color:#ff0000">Bilateral inguinal lymph node dissection (ILND)</span>'''
+**#*'''Lymphatic spread of penile carcinoma can be unilateral or bilateral to the inguinal lymph nodes'''
+**#*Approaches (2):
+**#**Open
+**#**Video-endoscopic surgery
+==== <span style="color:#ff0000">Palpable adenopathy</span> ====
+* '''Associated with metastasis in 43% of cases, secondary to inflammation in the remainder'''; can consider fine-needle aspiration to differentiate
+* '''Lymphadenectomy can be curative''' due to the prolonged locoregional phase before distant dissemination
+* '''Inguinal lymphadenectomy is still recommended'''
+** '''<span style="color:#ff0000">The superficial lymph node dissection should be bilateral even if adenopathy is unilateral at presentation</span>'''
+** '''<span style="color:#ff0000">Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.</span>'''
+* '''Exception is verrucous carcinoma, also known as a Buschke-Lowenstein tumor'''
+** Unlike penile squamous cell carcinoma, verrucous carcinoma of the penis has a very low likelihood of metastasis.
+** Palpable adenopathy in the context of verrucous carcinoma is very likely to be reactive and should be initially observed. Biopsy should be reserved unless the node remains persistently enlarged or grows over time.
+** '''Lymphadenectomy in the context of verrucous carcinoma should be reserved for cases of biopsy-proven metastases.'''
+==== <span style="color:#ff0000">Fixed inguinal lymph nodes (cN3)</span> ====
+* '''<span style="color:#ff0000">Neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders</span>'''
+==== Lymph node involvement (pN+) ====
+*'''Prognosis'''
+**'''Pathologic criteria associated with improved long-term survival after attempted curative surgical resection of inguinal metastases include:'''
+**# '''Unilateral involvement'''
+**# '''Minimal nodal disease (≤2 involved nodes in most series (pN1))'''
+**# '''No evidence of extra nodal extension of cancer (pN3)'''
+**# '''Absence of pelvic nodal metastases (pN3)'''
+**## '''i.e. pN1, and lack of features associated with pN2 and pN3'''
+* '''No anatomic or lymphangiographic studies demonstrating direct lymphatic drainage to the pelvic lymph nodes from the penis, which is evidenced by the lack of metastatic spread to the pelvic lymph nodes from a primary penile tumor in the absence of metastatic spread to the inguinal lymph nodes[https://link.springer.com/book/10.1007/978-3-319-60858-7]'''
+*'''<span style="color:#ff0000">Indications for pelvic lymph node dissection in patients undergoing inguinal lymph node dissection for curative intent (no pelvic adenopathy) (2):</span>'''
+*# '''<span style="color:#ff0000">≥2 positive inguinal lymph nodes</span>'''
+*# '''<span style="color:#ff0000">Extra-nodal extension is present</span>'''
+*## '''PLND in this setting serves as staging tool to identify patients who should be considered for adjunctive therapy'''
+*## '''PLND includes the distal common iliac, external iliac, and obturator groups of nodes.'''
+==== Summary of treatment strategies for nodal metastases ====
 {| class="wikitable"
 |'''Lymph node status'''
@@ Line 381: / Line 331: @@
 |'''Not recommended for nodal disease except as a palliative option'''
 |}
+'''2018 EAU Penile Cancer Guidelines'''
-==== Lymph node involvement ====
+=== Radiation ===
-*'''Pathologic criteria associated with improved long-term survival after attempted curative surgical resection of inguinal metastases include:'''
-*# '''Unilateral involvement'''
-*# '''Minimal nodal disease (≤2 involved nodes in most series (pN1))'''
-*# '''No evidence of extra nodal extension of cancer (pN3)'''
-*# '''Absence of pelvic nodal metastases (pN3)'''
-*## '''i.e. pN1, and lack of features associated with pN2 and pN3'''
-* '''<span style="color:#ff0000">Indications for pelvic lymph node dissection in patients undergoing inguinal lymph node dissection for curative intent (no pelvic adenopathy) (2):</span>'''
-*# '''<span style="color:#ff0000">≥2 positive inguinal lymph nodes</span>'''
-*# '''<span style="color:#ff0000">Extra-nodal extension is present</span>'''
-*## '''PLND in this setting serves as staging tool to identify patients who should be considered for adjunctive therapy'''
-*## '''PLND includes the distal common iliac, external iliac, and obturator groups of nodes.'''
-==== Radiation ====
 * '''An option for those with invasive SCC refusing surgical treatment'''
@@ Line 408: / Line 346: @@
 * '''Palliative radiotherapy among patients with inoperable inguinal nodes may provide some benefit'''
-==== Chemotherapy ====
+=== Chemotherapy ===
 * '''Treatment with a cisplatin-containing regimen in advanced metastatic penile cancer should be considered''' and this may facilitate curative resection. The optimal regimen has yet to be determined.
 * Among patients whose tumour progresses through chemotherapy, surgery is not recommended
-== Non-squamous penile malignant neoplasms ==
-* '''Extremely rare'''
-=== Basal cell carcinoma ===
-* Frequently encountered on other sun-exposed cutaneous surfaces, it is '''rare on the penis'''
-* Treatment is by local excision, which is virtually always curative
-=== Melanoma ===
-* Aggressive form of cancer but can be cured if diagnosed and treated with the appropriate surgical treatment at an early stage
-** '''Surgery is the primary mode of treatment'''; radiation therapy and chemotherapy are of only adjunctive or palliative benefit
-=== Sarcoma ===
-* Prone to local recurrence; regional and distant metastases are rare.
-* Superficial lesions can be treated with less radical procedures
-=== Extramammary Paget Disease ===
-* Appearance
-** Erythematous, eczematoid, well-demarcated area
-** Cannot be clinically distinguished from erythroplasia of Queyrat, Bowen disease, or carcinoma in situ of the penis
-** See Figure
-* Clinical presentation
-** Local discomfort, pruritus, and occasionally a serosanguineous discharge involving the penis, the scrotum, or even the perianal area
-* '''Behaves as a slow-growing intraepithelial adenocarcinoma'''
-** With time the cells may become invasive with dermal tumor deposits metastasizing to regional lymph nodes via dermal lymphatics penoscrotal
-* '''May be associated with other malignancies of the genitourinary tract, such as prostate, bladder, and renal malignancies and should be evaluated for their presence'''
-* '''Management'''
-** '''In most cases, only the skin and dermis must be resected with a gross margin of up to 3 cm'''. '''Positive margins may still occur, and frozen sections are recommended to guide the extent of resection.'''
-*** Patients with a positive surgical margin are at a higher risk for recurrence, and additional resection is advised
-** Local skin or scrotal flaps can be used to cover the defects.
-** In a minority of cases the tumor may invade deeper structures, necessitating more extensive resection and reconstruction
-** If inguinal adenopathy is present, radical node dissection is advised but prognosis is poor
-=== Adenosquamous carcinoma ===
-=== Lymphoreticular malignant neoplasm ===
-=== Metastases ===
-* Most often represent spread from a clinically obvious existing primary tumor.
-* Prognosis is poor, and therapy should be directed toward the primary tumor site histology and local palliation
-* '''Priapism is the most frequently encountered sign of metastatic involvement of the penis'''
-'''Lymphomatous infiltration of the penis is most likely secondary to diffuse disease'''
 == References ==
 * Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015
-* Brouwer, Oscar R., et al. "European association of urology-american society of clinical oncology collaborative guideline on penile cancer: 2023 update." ''European urology'' (2023).
+* [https://pubmed.ncbi.nlm.nih.gov/36906413/ Brouwer, Oscar R., et al. "European association of urology-american society of clinical oncology collaborative guideline on penile cancer: 2023 update." ''European urology'' (2023).]