Two7 79 Tumors of Penis

  1. Premalignant penile lesions (precursor lesions)?
    • Lesions sporadically associated with squamous cell carcinoma (SCC) of the penis:
    • • Bowenoid papulosis of the penis (HPV related)
    • • Male Lichen Sclerosus (Balanitis Xerotica Obliterans) - There are reports documenting the association of male LS with squamous cell carcinoma as well as with the development of carcinoma long after a lesion of LS has been treated.

    • Premalignant lesions (up to one-third transform to invasive SCC):
    • • Penile intraepithelial lesions
    • • Giant condylomata (Buschke-Löwenstein)
    • • Bowen’s disease
    • • Paget’s disease (intradermal ADK)

    Cutaneous Horn - It usually develops over a preexisting skin lesion (wart, nevus, traumatic abrasion, or malignant neoplasm) and is characterized by overgrowth and cornification of the epithelium, which forms a solid protuberance. Because this tumor may evolve into a carcinoma or may develop as a result of an underlying carcinoma, careful histologic evaluation of the base and close follow-up of the excision site are essential.
  2. What are penile intraepithelial neoplasia?
    These three lesions fall under the category of penile intraepithelial neoplasia (i.e., PeIN or PIN), also called as Carcinoma in situ (CIS). 

    • - Erythroplasia of Queyrat - if it involves the glans penis and prepuce (mucocutaneous epithelium) - red, velvety, well-marginated lesion
    • - Bowen disease - if it involves the penile shaft or the remainder of the genitalia or perineal region
    • - Bowenoid papulosis - histologic appearance similar to that of carcinoma in situ but a benign course

    Progression to invasive carcinoma in men with BD and EQ may occur in 5% to 33% of patients, respectively, if it is not treated.  Metastasis has rarely occurred. Cancer eradication with organ-preserving strategies is the goal of therapy.
  3. Virus-Related Penile Lesions
    • - HPV - Condyloma acuminatum, giant condyloma and bowenoid papulosis
    • - Human herpesvirus 8 - epidemic (AIDS-related) Kaposi sarcoma
  4. Note
    • - There is at present no recommendation for the use of HPV vaccination in boys
    • -   A diagnosis of penile Kaposi sarcoma is often associated with human herpesvirus 8 and should prompt an investigation into whether the patient is also infected with HIV or otherwise immunosuppressed
  5. What is condyloma acuminata?
    • Condylomata acuminata are soft, papillomatous growths typically considered to be benign
    • Also known as genital warts or venereal warts
    • Treatment of these lesions with podophyllin may induce histologic changes suggestive of carcinoma. Consequently, preliminary biopsy of large lesions that appear to be condylomata acuminata should precede any treatment with topical podophyllin.

    • Treatment
    • - Local treatment - (1) podophyllotoxin 0.5% solution or gel, (2) trichloroacetic acid 35% to 85%, (3) cryotherapy with liquid nitrogen, (4) electrofulguration, (5) CO2 laser therapy, and (6) imiquimod 5% cream
    • - imiquimod cream (5%) has become the topical treatment of choice for condyloma. Imiquimod is an immune modulator that enhances natural killer cell activity
    • - Circumcision
    • - Condylomata have been associated with squamous cell carcinoma of the penis
  6. What is Buschke-Löwenstein Tumor?
    • - Also called as Verrucous Carcinoma, Giant Condyloma Acuminatum
    • - The Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue. Buschke-Löwenstein tumor displaces, invades, and destroys adjacent structures by compression (pushing rather than infiltrating).  Aside from this unrestrained local growth, it demonstrates no signs of malignant change on histologic examination and does not metastasize.
    • - Elevated risk of malignant transformation towards squamous cell carcinoma
    • - Lymph node metastases are rare with verrucous carcinoma, and their presence probably reflects malignant degeneration in the primary lesion
    • - Either excisional biopsy or multiple deep biopsies are required to distinguish the lesion from true penile carcinoma. Treatment consists of excision, sparing as much of the penis as possible. Large lesions may necessitate total penectomy.
    • - Radiation therapy is ineffective for verrucous carcinoma
  7. Risk factors for carcinoma penis?
    • Phimosis 
    • Chronic penile inflammation (balanoposthitis related to phimosis), lichen sclerosus
    • Sporalene and ultraviolet A phototherapy for various dermatological conditions such as psoriasis
    • Smoking - Five-fold increased risk
    • HPV infection, condylomata acuminata
    • Rural areas, low socio-economic status, unmarried
    • Multiple sexual partners, early age of first intercourse - Three to five-fold increased risk of penile cancer
    • Penile trauma and tears
  8. Circumcision for prevention of penile cancer?
    • Phimosis - OR 11-16 vs. no phimosis.
    • Neonatal circumcision has been well established as a prophylactic measure that virtually eliminates the occurrence of penile carcinoma because it eliminates the closed preputial environment where penile carcinoma develops. The chronic irritative effects of smegma, a byproduct of bacterial action on desquamated cells that are within the preputial sac, have been proposed as a causative agent. 
    • The critical period of exposure to certain causative agents may have already occurred at puberty and certainly by adulthood, rendering later circumcision relatively ineffective as a prophylactic tool for penile cancer.
    • Although neonatal circumcision is highly protective for invasive penile cancer, it does not afford the same level of protection for CIS.
  9. Histological subtypes of penile carcinomas
    • Squamous cell carcinoma (SCC) - MC
    • Basaloid carcinoma - Poor prognosis, frequently early inguinal nodal metastasis, associated with HPV [@ corelate baseloid with basal cell ] 
    • Warty carcinoma - Good prognosis, metastasis rare
    • Verrucous carcinoma - Good prognosis, no metastasis
    • Papillary carcinoma - Good prognosis
    • Sarcomatoid carcinoma - Very poor prognosis, early vascular metastasis
    • Mixed carcinoma

    Most tumors of the penis are squamous cell carcinomas  demonstrating keratinization, epithelial pearl formation, and  various degreesof mitotic activity
  10. Why HPV is higher in unccircumcised men?
    • It is thought that, moist subpreputial space provides a more optimum environment of infection by virus than dried environment 
    • Circumcised men also clear HPV faster
  11. What is the role of vaccine prevention in carcinoma penis. (TU 75,5)

    Role of the vaccine in carcinoma penis?
    • Prophylactic HPV vaccines - 
    • - Cervarix - HPV 16/18 vaccine 
    • - Gardasil - Quadrivalent HPV 16/18/6/11 vaccine
    • - Gardasil 9 - Nanovalent [@ Cervix - two lips, Garda - gada - 4 wheels] 

    • Efficacy of preventing HPV infection among HPV-negative young women and men has been demonstrated
    • HPV-16 appears to be the most frequently detected type in  primary carcinomas and has also been detected in metastatic  lesions
  12. Why HIV less in circumcision males?
    Circumcision reduces the risk of men acquiring HIV infection - superficial skin layers of penis contain langerhans cells targeted by HIV and circumcision reduces the number of these cells
  13. Clinical features of carcinoma penis?
    Penile lesion - ranges from a relatively subtle induration or small excrescence to a small papule, pustule, warty growth, or more luxuriant exophytic lesion. It may appear as a shallow erosion or as a deeply excavated ulcer with elevated or rolled-in edges. Phimosis may obscure a lesion and allow a tumor to progress silently. Eventually, erosion through the prepuce, foul preputial odor, and discharge with or without bleeding call attention to the disease.

    Pain does not develop in proportion to the extent of the local destructive process and usually is not a presenting complaint.

    Urinary retention or urethral fistula from local corporeal involvement is a rare presenting sign.

    Metastatic enlargement of the regional nodes eventually leads to skin necrosis, chronic infection, and sepsis, or hemorrhage secondary to erosion into the femoral vessels.

    Distant metastases in the absence of regional node metastases are unusual

    Delay - Explanations include embarrassment, guilt, fear, ignorance, and personal neglect. This level of denial is substantial, given that the penis is observed and handled on a daily basis
  14. Common sites of Penile carcinoma?
    • Glans - 48% 
    • Prepuce - 21% 
    • Glans and Prepuce - 9% 
    • Coronoal sulcus - 6% 
    • Shaft <2%

    This distribution of lesions may be the result of constant exposure of the glans, coronal sulcus, and interior prepuce to irritants (e.g., smegma, HPV infection) within the preputial sac, whereas the shaft is relatively spared. 

    • Image Upload 1
    • This is phallus of lord shiva, and having Phallus is reward in hindu
  15. How to do biopsy in suspected case of carcinoma penis?
    A dorsal slit is frequently necessary to gain adequate exposure of the lesion for satisfactory biopsy

    • Take small wedge biopsy
    • Take biopsy at margin of normal tissue and tumor 
    • Adequate depth of tissue should be taken, if you take only superficial part, only nectrotic tissue may be present 

    Local excision is not done ?

    • Note -
    • - Excisional biopsy - entire lesion is removed 
    • - Incisional biopsy - only part of the lesion is removed
  16. Recommendations for the pathological assessment of tumour specimens EAU 2020?
    • The pathological evaluation of penile carcinoma specimens must include an assessment of the HPV status. Strong
    • The pathological evaluation of penile carcinoma specimens must include a diagnosis of the squamous cell carcinoma subtype. Strong
    • The pathological evaluation of penile carcinoma surgical specimens must include an assessment of surgical margins including the width of the surgical margin. Strong
  17. Lab investigations in carcinoma penis?
    Anemia, leukocytosis, and hypoalbuminemia may be present in patients with chronic illness, malnutrition, and extensive suppuration at the area of the primary and inguinal metastatic sites.

    Azotemia may develop secondary to urethral or ureteral  obstruction

    • Hypercalcemia - 
    • - Hypercalcemia without detectable osseous metastases
    • - function of the bulk of the disease, often associated with inguinal metastases and may resolve after excision of involved inguinal nodes
    • - Parathyroid hormone and related substances may be produced by tumor and metastases that activate osteoclastic bone resorption
  18. TNM Penile Cancer?
    Tis - Carcinoma in situ (penile intraepithelial neoplasia)

    Ta - Noninvasive localized squamous cell carcinoma

    • T1
    • - Glans: Tumor invades lamina propria
    • - Foreskin: Tumor invades dermis, lamina propria, or dartos fascia
    • - Shaft: Tumor invades connective tissue between epidermis and corpora regardless of location
    • - T1a Tumor is without lymphovascular invasion or perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid)
    • - T1b Tumor exhibits lymphovascular invasion and/or perineural  invasion or is high grade (i.e., grade 3 or sarcomatoid)

    • T2
    • - Tumour invades corpus spongiosum  (either glans or ventral shaft) with or without invasion of the urethra

    • T3
    • - Tumour invades corpus cavernosum with or without invasion of the urethra

    • T4
    • - Tumour invades other adjacent structures  (i.e., scrotum, prostate, pubic bone)

    • N1 Palpable mobile unilateral inguinal lymph node
    • N2 Palpable mobile multiple or bilateral inguinal lymph nodes
    • N3 Fixed inguinal nodal mass or pelvic lymphadenopathy, unilateral or bilateral

    M1 Distant metastasis

    • pN1 - one or two inguinal lymph nodes
    • pN2 - more than two unilateral inguinal nodes or bilateral inguinal lymph nodes
    • pN3 - pelvic lymph node(s), unilateral or bilateral or extranodal extension of regional lymph node metastasis

    • Note
    • -   Buck fascia acts as a temporary natural barrier to local extension of the tumor, protecting the corporeal bodies from invasion. Penetration of Buck fascia and the tunica albuginea permits invasion of the vascular corpora and establishes the potential for vascular dissemination
    • -  The most common metastatic sites are the lung, bone, and liver
    • -   In the seventh edition structures between the epidermis and the tunica albuginea were designated by the term “subepithelial connective tissue. In the eighth edition the specific layers are designated
  19. Stage Ta Definition?
    • In the seventh edition TNM category Ta referred to “non-invasive verrucous carcinoma.” This term was misleading to some pathologists who thought this would apply to all cases of verrucous carcinoma. The great majority of verrucous carcinomas are destructive, but the invading front is smooth and pushing with the depth of invasion often difficult to assess.
    • In the current classification, the Ta category is expanded and applies to
    • (1) pure (well or completely sampled) verrucous carcinomas with no overt destructive invasion and
    • (2) noninvasive papillary, warty, basaloid, or mixed carcinomas. These rare, noninvasive surface-based tumors are somewhat analogous to noninvasive (pTa) papillary urothelial neoplasms
  20. Tumor Grading of carcinoma penis?
    • Modifications of the Broder’s grading system (traditional) 
    • - G1 Well differentiated
    • - G2 Moderately differentiated
    • - G3 Poorly differentiated
    • - G4 Undifferentiated

    [@ Broder - broader - 4 grades, WHO - smaller, 3 grades] 

    • WHO/ISUP grading system 2016
    • - Grade 1 - well differentiated
    • - Grade 2 - moderately differentiate
    • - Grade 3 - poorly differentiated

    • Grade 1 and 3 is usually straightforward. Cases not typical for grade 1 or 3, belong to grade 2.
    • The majority of verrucous, papillary NOS, cuniculatum and pseudohyperplastic carcinomas are well differentiated or grade 1 tumors. Sarcomatoid, pseudoglandular, lymphoepithelioma -like, clear cell and basaloid carcinomas are usually poorly differentiated or grade 3
    • In tumors showing more than one grade, any proportion of grade 3 is sufficient to place the tumor under this category.
  21. Conclusion of WHO/ISUP 2016?
    • - new classification of penile squamous cell carcinoma separating the variants in HPV and non-HPV -related
    • - HPV -related neoplasms, which may be recognized by their histological features, p16 was recommended as a surrogate indicator of HPV.
    • - three -tier grading system, was recommended for penile squamous cell carcinomas

    HPV positive status have better outcome  - ref?
  22. Features of malignant LN?
    • Fine-needle aspiration for cytology is performed if one or more of the following are detected:
    • • Increased size
    • • Abnormal shape - Rounded, with a short-long axis ratio <2, Eccentric cortical hypertrophy
    • • Absence of an echogenic hilum. If hilum is full of fat, it is lesslikely malignant 
    • • Hypoechogenicity of the node compared with adjacent muscle
    • • Lymph node necrosis
    • • Abnormal vascularity on power Doppler

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  23. FNAC in Carcinoma penis?
    Some studies have suggested that in men with penile cancer, fine-needle aspiration cytology (FNAC) of suspicious nodes should be the first investigation in clinically node-negative patients at high risk for occult metastasis. FNAC could also be used in patients with clinically palpable nodes.

    • Sensitivity - 50% to 100%
    • Specificity - 90% to 100%

    If a tumor is confirmed, therapeutic ILND can be performed instead of DSNB and overlying skin and tissues containing the needle tract should be removed with the nodal tissue.

    If FNAC is negative, it can be repeated if suspicion of lymph node involvement remains.
  24. Imaging in penile cancer?
    • T staging
    • -  the primary tumor and the inguinal lymph nodes are readily assessed by palpation  
    • - Ultrasound (US) can give information about infiltration of the corpora.
    • - Magnetic resonance imaging (MRI) with an artificially induced erection can help to exclude tumour invasion of the corpora cavernosa if preservation of the penis is planned. EAU 2020
    • - Perform a physical examination, record morphology, extent and invasion of penile structures. Strong EAU 2020
    • - Obtain a penile Doppler ultrasound or MRI with artificial erection in cases with intended organ-sparing surgery.Weak EAU 2020
    • - Compared with MRI and ultrasonography, computed tomography (CT) has poor soft-tissue resolution and has not been useful for imaging the extent of the primary tumor 

    Nodal staging -  Physical examination of the inguinal region remains the clinical gold standard for evaluating the presence of metastasis in the nonobese patient

    • If nodes are not palpable
    • - current imaging techniques are not reliable in detecting micrometastases
    • -   An important caveat is that CT may have a role in examination of the inguinal region in obese patients or in those who have had prior inguinal surgery, in whom the physical examination may be unreliable
    • - - MRI with iron nanoparticles - detect inguinal metastasis in more than 90% of patients with positive ILN disease. Iron nanoparticles are injected in peritumor area that are phagocyted by tumor-associated macrophages, promoting a negative signal in T1 MRI sequences inside the positive nodes. Unfortunately, no confirmatory studies were performed using this agent, and the compound is not currently available for routine use. 

    • If nodes are palpable
    • - CT abdomen and chest is recommended. Alternatively, stage with a PET/CT scan.Strong EAU 2020.
    • - Sensitivity and specificity of USG is around 50% for LN 

    • Distant metastases
    • Clinical examination
    • Biochemical determinations (liver functions, calcium) CT scan of the chest, abdomen, pelvis; bone scintigraphy; or CT/PET scan (as indicated)

    SUV value of PET have prognostic value
  25. What are different types of surgical options in management of carcinoma penis. Describe its indications for surgical LN dissection. (TU 69-10)

    Principles of penile preservation surgery?
    • Surgical amputation of the primary tumor remains the oncologic gold standard for rapid definitive treatment of the penile primary tumor. 
    • Amputation decreases sexual quality of life - Approximately 55% of penile cancer patients are 60 years of age or younger and 30% are 55 years of age or younger.

    • Patients with penile primary tumors exhibiting favorable histologic features (stages Tis, Ta, T1; grade 1 and grade 2 tumors) are at a lower risk for metastases. These patients are also best suited for organ-sparing or glans-sparing procedures.
    • Amputation remains the standard for large or deeply invasive lesions, to gain rapid tumor control
    • Aim of surgery is complete removal of tumor and preserve glans sensation where possible or at least to maximize penile shaft length

    • Rationale for penile preservation 
    • - offers patients a penis capable of micturating and possibly sexual functions 
    • - lessens the psychosocial impact on the patients 
    • - Local recurrence rates overall after organ preservation are higher than with traditional amputation; however, when local recurrences are detected and treated, early survival does not appear to be adversely affected. 
    • - Local recurrence rates range from 0 to 8%
    • - most cancers are distally located and skin lesions are rare 

    It is extremely important that the patient understands the risk of local recurrence and its compliant with regular follow up. Most recurrrences occurs in first 5 years

    • Patients suitable for organ sparing surgery - ref? 
    • Small solitary lesion
    • Non invasive or superficially invasive (no corpora cavernosal invasion)
    • Away from external urethral meatus
    • <50% poorly differentiated, no LV invasion
  26. Methods of organ preservation?
    Surgical techniques


    • Glans resurfacing 
    • - also known as glans stripping
    • - subdermal dissection of the skin and subepithelial connective tissue off the underlying corpora spongiosa is performed
    • - frozen section of spongiosal tissue to exclude invasion, split thickness skin graft 

    • Wild local excision 
    • - for lesions upto T1a 
    • - May be done on the glans or the shafft 
    • - May be closed by primary closure, skin graft or preputial or shaft skin flap 

    • Glansectomy 
    • - for T1b and T2 tumors confined to the glans 

    Partial penectomy

    • Laser therpay -
    • - for lesion upto T1, has been reported for T2 as well 
    • - CO2 laser - depth of penetration (limited to 0.1 mm), recurrence rate as high as 50%
    • - Nd:YAG laser -  depth of  penetration 6 mm, recurrence  rates after laser ablation have been reported to be 7.7% for penile CIS and have ranged from 10% to 25% for T1 lesions

    • Mohs micrographic surgery
    • - layer-by-layer complete excision of the penile lesion in multiple sessions (fixed tissue technique), with microscopic examination of the undersurface of each layer
    • - its sequential microscopic guidance offers improved precision and control of the negative margin while maximizing organ
    • preservation 
    • -   Mohs microsurgery, as currently performed, may offer no additional benefit over surgical excision with intraoperative frozen-section assessment of margin status

    • Non-surgical techniques - 
    • - topical therapy - 5-FU, Imiquimod, topical therapy should not be repeated after a recurrence 
    • - Radiotherapy for lesions < 4 cm
  27. Negative margin in partial penectomy?
    Several studies have challenged the dictum establishing that a 2-cm surgical margin is required for all patients undergoing partial penectomy.

    • The maximum proximal histologic extent is
    • - 5 mm for grade 1 and grade 2 tumors
    • - 10 mm for grade 3 tumors

    “Skip” lesions were not encountered in carcinoma penis

    Its always good idea to do frozen section in organ preservation surgery - the skin, corpora and urethra should be sampled separately 

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  28. Predictive factors for relapse after organ preserving penectomy?
    • Positive or close - <1mm surgical margin 
    • Corporal invasion 
    • LV invasion
  29. Principles of partial penectomy?
    • Partial or total penectomy should be considered in patients exhibiting adverse features for cure by organ-preservation strategies
    • - tumors of size 4 cm or more
    • - grade 3 lesions
    • - invading deeply into the glans urethra or corpora cavernosa

    Often the length preserved is adequate for the micturation but not for the sexual function 

    • Options for penile lengthening
    • - divide suspensory ligament
    • - division of the peno-scrotal web horizontally and suturing it vertically
    • - suprapubic fat pad excision
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  30. Partial Penectomy method?
    Approximately 3 cm has been suggested as a minimal acceptable penile length for optimal functional outcomes. Voiding from a penile stump that is too short to control a urinary stream may be less desirable than voiding through a perineal urethrostomy. 

    Circumferential incision is made along the penile shaft skin 1.5 to 2 cm proximal to the lesion

    The urethra is dissected from the corpus spongiosum distally for a distance of approximately 1 to 1.5 cm and transected. 

    The urethra is spatulated on its dorsal surface to facilitate reconstruction and prevent stenosis of the neourethra

    The ends of both corpora are closed transversely with interrupted absorbable 2-0 sutures that incorporate the septum
  31. Complete penectomy steps?
    Exaggerated dorsolithotomy

    • Dissect through the subcutaneous tissue dorsally with the electrocautery.
    • Plan to transect the corpora near the level of the
    • pubis. Divide the suspensory ligaments, ligate superficial dorsal vasculature of the penis, 
    • Open the Buck fascia on the ventral aspect of the penis to identify the urethra. 
    • Dissect the urethra sharply away from the corporal bodies, leaving plenty of length to reach the perineum for the  eventual perineal urethrostomy.
    • Divide the urethra sharply to maintain healthy blood supply,  Continue the dissection of the urethra off of the proximal corporal bodies back to the pubic ramus Sharply excise any excess urethra and then spatulate the urethra at the 12 o’clock position Using a combination of sharp and  electrocautery dissection, dissect the corporal bodies back to their insertion on the pubic rami. Divide the corporal bodies with the electrocautery and then oversew the stumps individually with a running 2-0 polygalactin suture. Because often this is a relatively deep hole, a 2-0 polygalactin on a UR-6 needle can be helpful to oversew the stumps
    • Make a 1- to 2-cm elliptical incision or an inverted Y incision in the perineum with a #15 scalpel blade and carry this through the dermis and subcutaneous fat. Pass a tonsil clamp through this perineal incision into the defect created from the penectomy for transposition of the urethra to the perineum. 
    • Sharply excise any excess urethra and then spatulate the urethra at the 12 o’clock position. The urethra should rest comfortably in the perineum and not have any tension. “Mature” the urethrostomy by placing interrupted 4-0 monofilament poliglecaprone sutures in a circumferential fashion around the urethra starting at the crotch of the spatulation on the urethra 

    QQQ - is testis removed in total penectomy, there is no use of bullet when there is no gun? - EAU, Campbell does not include orchidectomy with penectomy 

    Emasculation conventionally involves the amputation of penis and testicles and all or part of the scrotum
  32. Minimal acceptable length for penile length?
    3 cm, if penile stump is too short – go for total penectomy
  33. Adverse prognostic factors?
    >3 inguinal nodes, perinodal infiltration, pelvic node involvement
  34. Risk stratification of chance of lymph node metastasis - NCCN 2018
    • Very Low-risk - Tis, Ta
    • Low to Intermediate risk - T1a
    • High-risk - T1b,  and above

    Ficarra's nomogram - is also commonly used for risk stratification
  35. 5 year survival rate
    • - 95% in negative nodes
    • - 76% in one inguinal node positive
    • - 0% in pelvic nodes positive
  36. Principles of LN management in carcinoma penis?
    The presence and the extent of metastasis to the inguinal region are the most important prognostic factors for survival in patients with squamous penile cancer. These findings affect the prognosis of the disease more than do tumor grade, gross appearance, and morphologic or microscopic patterns of the primary tumor. 

    The treatment of regional lymph nodes is crucial for the survival of the patient. A surveillance strategy carries considerable risk as regional lymph node recurrence dramatically reduces the chance of long-term survival. Invasive staging by modified inguinal lymphadenectomy or dynamic sentinel node biopsy is recommended for penile cancers pT1G1 and higher.

    Unlike with many other genitourinary tumors, which mandate systemic therapeutic strategies once metastasis has occurred, lymphadenectomy alone can be curative and should be performed. The biology of squamous penile cancer is such that it exhibits a prolonged locoregional phase before distant dissemination, providing a rationale for the therapeutic value of lymphadenectomy. 

    Immediate resection of clinically occult lymph node metastases is associated with improved 5-year survival rates (85% vs. 35%) when compared with delayed resection of involved nodes at the time of clinical detection. Nonetheless, if the tumor has spread to the pelvic nodes, long-term survival is less than 10%. 

    • Low risk, nonpalpable - observation
    • Intermediate risk (T1b), high risk (T2 and above) - ILND
    • Any patient with a positive lymph node on dynamic sentinel node biopsy (DSNB), should undergo ILND

    Moreover, there is evidence that delays in the treatment of the ILNs of more than 12 weeks will negatively impact a patient’s chances of survival significantly (5-year disease specific survival of 64.1% vs. 39.5%). 

    Approximately 25% of patients with nonpalpable lymph nodes will have lymphatic metastases. 

    For palpable disease, 30% to 50% of these nodes are secondary to associated inflammatory conditions and not to metastases. Traditionally, it was stated that the timing to differentiate between infection and metastasis was 6 weeks of antibiotic treatment. [@ 1/4th of non palpable lesions have micrometastasis, 1/2 of palpable nodes may not have metastasis] 

    Recent evidence - late ILND and positive node disease are significant factors for recurrence and decreased survival.
  37. Write the algorithm for management of ilioinguinal LN involvement in a patient with squamous cell carcinoma of penis. (TU 75-10)

    LN management for low-risk primary disease?
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    • 3) If 2 or more positive ipsilateral inguinal nodes or extranodal extension found

    Although treatment of the primary tumor and a period of antibiotics are useful to help sterilize the inguinal region, this practice is no longer advocated as a tool to select patients who either should or should not undergo lymphadenectomy.

    • [@ Tis, Ta - for palpable node, first Antibioitics, then if persistent go for FNA, if negative - excisional biopsy.
    • For T1a - for palpable node, go for FNA, if negative go for excisional biopsy]
  38. LN management for Intermediate and risk primary disease?
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    Response based on RECIST criteria - ref? 

    Among patients who progress through chemotherapy, surgery is not recommended. 

    When nodal ulceration or local skin invasion is noted, surgery can be performed for symptom palliation or to avoid death caused by femoral bleeding. 

    For inguinal LN dissection, always do bilateral. Patient to whom when you can do unilateral is one who lost in follow up for LN dissection after primary surgery, and later presents with unilateral LN.

    • Note 
    • - NCCN 2020 recommends percutaneous LN biopsy in all cases palpable LN unilateral or bilateral, mobile or fixed, the only condition they recommend direct ILND is high risk primary in unilateral LN<4 cm (mobile)
  39. Should bilateral ILND be performed in patients with unilateral lymphadenopathy some time after the initial presentation and treatment of the primary tumor?
    It is generally believed that bilateral node dissection in this setting is not necessary. The recommendation of unilateral rather than bilateral node dissection with delayed presentation of unilateral lymphadenopathy is supported by the elapsed disease-free interval of observation on the normal side. If one assumes that nodal metastases will enlarge at the same rate, the clinical palpation of nodal metastases, if present in both groins, should appear at approximately the same time. The absence of clinical adenopathy on one side despite prolonged observation suggests freedom from disease on that side.
  40. Indications of pelvic LN dissection?
    Ipsilateral pelvic lymphadenectomy if two or more inguinal nodes are involved on one side (pN2) or if extracapsular nodal metastasis (pN3) reported. Strong EAU 2020 (Note - N2 in EAU is >2 lymph nodes, but here it is confusing) 

    • 3 or more Inguinal Lymph nodes (NCCN 2019)
    • Ipisilateral pelvic LN dissection if -  3 or less inguinal LN dissection, no suspicion of contralateral pelvic LN involvement in imaging. Bilateral pelvic LN dissection if 4 or more inguinal LNs are positive. (NCCN 2019)

    • Bulky inguinal LN metastasis >3cm 
    • Cloquets LN +ve on frozen section 

    When all factors are present - Pelvic LN metastasis in 57% vs 0% when none of these present. In summary - if inguinal LN are positive, we have to do pelvic LN dissection.
  41. Radiation Therapy for the Primary Lesion?
    • Primary radiation therapy has curative potential and may permit preservation of penile form and function. If local control is not achieved, salvage surgery may still be curative, and therefore in a subset of men with penile cancer, initial radiation represents a reasonable treatment strategy.
    • External-beam radiotherapy and interstitial brachytherapy can be used to treat the primary penile tumor. Before radiation therapy, circumcision is necessary to expose the lesion, to allow resolution of any surface infection, and to prevent preputial edema and subsequent phimosis. In many cases, circumcision may also significantly debulk the primary tumor.

    For noninvasive or very superficial tumors, a surface mold containing iridium-192 wires can be constructed. Plastic mold is worn in close apposition to the penile shaft for several hours per day for a period of 7 to 10 days for an adequate surface dose of 60 Gy with rapid fall-off at a depth.

    The two most common late side effects associated with radiotherapy are meatal stenosis and soft-tissue ulceration
  42. Radiation therapy for nodal disease?
    • Radiotherapy Not recommended for nodal disease except as a  palliative option.Strong  EAU 2020. Unresectable lymph nodes may be rendered operable by neoadjuvant chemotherapy or chemoradiation.
    • Palliative radiotherapy may be beneficial for metastatic disease.

    For N2-3 disease, NCCN recommends chemotherapy or chemoradiation

    • Following patients may benefit from adjuvnat radiotherapy
    • - Bulky inguinal LN metastasis without pelvic LN metastasis 
    • - Extranodal extension 
    • - Patient unfit or unwilling for chemo 
    • - Human papilloma virus - new studies find that radiotherapy is more effective in HPV positive cases - ASCO 2020
  43. Penile reconstructive surgery?
    During surgery - ventral phalloplasty - give 1-1.5 cm extra length
  44. Chemotherapy in penile cancer?
    • Offer patients with pN2-3 tumours adjuvant chemotherapy after radical lymphadenectomy (three to four cycles of cisplatin, a taxane and 5-fluorouracil or ifosfamide). Strong
    • Offer patients with non-resectable or recurrent lymph node metastases neoadjuvant chemotherapy (four cycles of a cisplatin- and taxane-based regimen) followed by radical surgery. Weak
    • Offer palliative chemotherapy to patients with systemic disease. Weak

    • Single agent chemotherapy 
    • - Cisplatin
    • - Bleomycin - not recommended due to pulmonary toxicity 
    • - Methotrexate 

    • Combination chemotherapy
    • -  TIP regimen (Paclitaxel, Ifosfamide and cisplatin) - for Neo adjuvant chemotherapy. Objective response after 2 cycle, response rate 44-50%  
    • - TPF regmine (docetaxel (Taxotere), cisplatin (Platinol), and fluorouracil. Also called DCF),  for locally advanced or metastatic penile cancer, 3-4 cycles. 

    [@ TIP TUF (TPF)]

    (in NAMS, 4 cycles chemotherapy, each cycle costs around 24000)
  45. In which patients will you consider NACT?
    • EAU 
    • - Fixed inguinal nodes 
    • - Relapsed nodes after groind dissectin 
    • - Unresectable primary tumor 

    • NCCN - NCCN wants to give to larger number of patients 
    • - Unilateral inguinal node >4cm, 
    • - Unilateral inguinal node <4cm, fixed 
    • - Bilateral inguinal nodes 
    • - Enlarged pelvic nodes 
    • - Unresectable primary tumor

    In post chemo - there is a lot of fibrosis and dissectin may be diffficult - may need vascular grafts
  46. if you are considering non surgical treatment, is is necessary to treat the primary upfront?
    Yes, it is preferable
  47. Novel therapies in penile cancer?
    • Targeted therapy - EGFR overexpression in penile SCC, Cetuximab, dacominitinib are being trialled
    • Intraarterial chemotherapy
    • Immunotherapy
  48. Local inguinal LN recurrance after inguinal LN dissection, management?
    If no pelvic LN, and metastasis in other sited, radical iliofemoral LN dissection, may need flap procedure - case of Kancha Tamang - plan Dr BRL 

    EAU - NACT
  49. Metastasic deposit to penis?
    • Prostate 
    • Bladder
  50. Recommendations for follow-up of the primary tumour EAU 2020
    • Follow-up after curative treatment in penile carcinoma, as in any malignant disease, is important for two reasons:
    • • early detection of recurrence allows for potentially curative treatment;
    • • the detection and management of treatment-related complications.

    Local recurrence does not significantly reduce long-term survival if successfully treated, while inguinal nodal recurrence leads to a drastic reduction in the probability of long-term disease-specific survival.

    • Penile preserving treatment -
    • - three monthly for 2 years
    • - six monthly from 3-5 years
    • - Examination - Regular physician or self-examination, Repeat biopsy after topical or laser treatment for penile intraepithelial neoplasia.

    • Amputation
    • - three monthly for 2 years
    • - yearly from 3-5 years
    • - Examination - Regular physician or self-examination
  51. Recommendations for follow-up of the inguinal lymph nodes
    • Surveillance
    • - three monthly for 2 years
    • - six monthly for 3-5 years
    • - Examinations - Regular physician or self-examination.

    • pN0 at initial treatment
    • - three monthly for 2 years
    • - yearly from 3-5 years
    • - Examination - Regular physician or self-examination. Ultrasound with fine-needle aspiration biopsy optional.

    • pN+ at initial treatment
    • - three monthly for 2 years
    • - six monthly for 3-5 years
    • - Examination - Regular physician or self-examination. Ultrasound with fine-needle aspiration cytology optional, computed tomography/magnetic resonance imaging optional.

    - Minimum duration to follow up in all penile cancers, - five years
  52. Summary of follow up
    • Minimum duration of follow up is 5 years 
    • For first 2 years - follow up every 3 months 

    • For next 2-5 years 
    • 6 monthly for 
    • - penile preservation 
    • - surviellence 
    • - N+ 
    • 1 yearly 
    • - Amputation 
    • - N0 case 

    • Examination include 
    • - regular physical and self examination 
    • - USG/FNAC optional in N0 
    • - USG/FNAC, CT/MRI in N+ cases
Card Set
Two7 79 Tumors of Penis