THE MANAGEMENT OF PENILE CANCER. PowerPoint

This PowerPoint includes all the relevant information and science about penile cancer and its management. Information is based on Campbell 12th edition and EAU 2024 updated guidelines.

1. PENILE CANCER Dr. Chipili B . Bsc.HB, MBChB, FZCMS (Urology)

2. Dr.Chipili B . “A life touched by cancer is not a life destroyed by cancer. Penile cancer is 100% curable when treated early”

3. Introduction Generally considered uncommon malignancy especially in developed countries Rare in Europe and North America (0.4% to 0.6%) Constitutes a substantial health concern in many African, South American and Asian countries (up to 10% of all cancers in men) Penile cancer has significant impact on the quality of life The significant emotional, social and physical needs should be addressed early in a holistic and multidisciplinary approach

4. Epidemiology The incidence of penile cancer increases with age The peak incidence is in the 6 th decade of life but does occur in younger patients It is most common in regions with a high prevalence of human papilloma virus (HPV) One third to half of the penile cancers are attributed to HPV related carcinogenesis

5. Risk factors Lack neonatal circumcision Phimosis Chronic penile inflammation Lichen sclerosis Multiple sexual partners HPV infection Ultraviolet A phototherapy Smoking Low socioeconomic status

6. Prevention strategies for penile cancer Neonatal circumcision Good penile hygiene Avoidance of HPV infection Avoidance of smoking HPV vaccination

7. Premalignant cutaneous lesions HPV related Bowenoid papulosis Condylomata acuminata Boschke-Lowëstein Non HPV related penile premalignant lesions Cutaneous horn Lichen sclerosus (Balanitis xerotica obliterans)

8. Penile intraepithelial neoplasm (PEIN or PIN) Carcinoma in situ of the penis is referred to as penile intraepithelial neoplasm Considered the precursor lesion for penile SCC When it involves the glans penis or prepuce its called Erythroplasia of Queyrat Carcinoma in situ involving the penile shaft, remainder of the genitalia or perineum is called Bowens disease The two entities are histologically the same but differ in location If not treated the risk of developing invasive carcinoma is about 5%

9. Presentation of malignant lesion Primary penile lesion Nonhealing ulcer Ulcer/ Induration concealed by phimosis Fungating mass Inguinal lesion Inguinal nodal mass Fungating ulcer in the groin Distant metastasis Lung, liver, bone etc.

10. Natural history of penile cancer Usually begins as a small lesion (papule, pustule or warty growth) It then gradually progresses to involve the whole glans and entire shaft of the penis with invasion of the corpora cylinders The earliest route of dissemination is the lymphatic spread to regional inguinal lymph nodes Superficial nodes are involved first followed by the deep nodes and eventually the pelvic nodes Clinically detectable distant metastasis to the lung, liver, bone and brain are uncommon

11. Diagnosis of penile cancer Requires a high index of clinical suspicion from history and physical examination Confirmation of diagnosis for carcinoma is done by histopathology A biopsy of the primary tumor should be obtained only when malignancy is not clinically obvious Histopathology is also necessary when non surgical treatment is planned (e.g. topical agents, radiotherapy or laser surgery)

12. Role of imaging In penile cancer the primary tumor and lymph nodes are best assessed by palpation MRI scan can be done if there is uncertainty about cavernosal invasion (cT3) where organ sparing treatment is considered If MRI is not available U/S scan can be used Currently there are no noninvasive staging options reliable enough to detect micro-metastasis in clinically non palpable inguinal lymph nodes Imaging of the inguinal lymph nodes should not be routinely used CT or MRI can be useful in evaluating inguinal nodes in obese patients or those with prior inguinal surgery

13. Diagnostic delays Penile cancer management is complicated by diagnostic delay The delay may be associated to feeling of embarrassment, guilt, fear, ignorance and personal neglect by penile cancer patients The delay by physicians in initiating diagnosis and treatment is also considerable Most patients are treated with prolonged courses of antibiotics before diagnostic and therapeutic interventions are instituted

14. Pathology Squamous cell carcinoma accounts for 95% of the penile cancer Other rare malignant lesions of the penis include Melanocytic Mesenchymal Lymphomas Metastases

15. Pathology Squamous cell carcinoma histological subtypes Classic Papillary Verrucous Warty Basaloid Sarcomatoid

16. Pathology report The pathology report for penile cancer must state the following Histological type and subtype Grade of the tumor Anatomical site of the primary tumor Growth pattern Depth of invasion Perineural and Lymphovascular invasion Invasion of the corpus spongiosum/cavernosum Invasion of the urethra Surgical margin status P16 immunohistochemistry results

17. Staging of penile cancer

18. Staging of penile cancer

19. Grading of penile cancer

20. Principles of management of penile cancer The management of penile cancer involves management of both the primary tumor and the regional lymph nodes The management of the primary tumor depends on location and staging It can be organ preserving or non organ preserving Management of inguinal lymph nodes can be observation, surgical staging or surgical extirpation Surgical staging is most reliable staging procedure for non palpable nodes but associated with highest morbidity

21. Management of the primary tumor The main aim of treatment is complete removal of the tumor balanced against optimal organ preservation without compromising oncological control Treatment of the primary tumor can be organ preserving and non organ preserving Organ preserving include topical, radiotherapy, laser, circumcision, wide local excision, Moh's surgery, glans resurfacing and glansectomy Non organ preserving are the amputative surgeries such as partial and total penectomy with urine diversion

22. Management of the primary tumor Generally primary penile tumors with favorable histological features (stages Tis, Ta and T1; grades 1 and 2) have low risk of metastasis These tumors are best managed with organ preserving procedures Tumors exhibiting adverse features for cure (size ≥ 4cm, grade 3, invasion of the corporal bodies or glans urethra) are managed with non organ preserving procedures Tumor invading the corporal bodies of the penile shaft is locally advanced Amputation is the standard of care for locally advanced penile cancers

23. Management of noninvasive disease (PeIN,Ta) The first line treatment option for non invasive disease is topical treatment with imiquimod or 5-fluorouracil (5-FU) Circumcision is the primary surgical option for lesions on the foreskin Close monitoring is advocated before any additional treatment Laser ablation is an alternative treatment option Extensive/residual or recurrent PeIN after topical or ablative therapy can be treated by surgical excision or glans resurfacing

24. Management of invasive disease confined to the glans (cT1/T2) The treatment options for invasive disease confined to the glans penis depends on the tumor size, stage, grade, localization and patient preference Minimal resection margins (i.e. >1 mm) have been shown to be oncologically safe Organ sparing surgeries are the preferred treatment options when feasible (circumcision, wide local excision, glans resurfacing, glansectomy) Despite higher recurrence rates compared to amputation the impact on long term survival is minimal

25. Management of local recurrence after organ sparing surgery A second organ sparing surgery can be performed in the absence of corpus cavernosal invasion In large or high stage recurrence partial or total penectomy is required provided the lesion is resectable

26. Management of locally advanced disease (cT3/T4) Amputative surgery (Partial or total penectomy) is the gold standard treatment for locally advanced disease (stage ≥ cT3) Total penectomy is preferred over partial penectomy when residual stump after resection of tumor free margins will result in either; Inability to void upright or without wetting the perineum Inability to perform satisfactory sexual function Nonresectable advanced primary lesions are managed with induction chemotherapy followed by surgery in responders or chemoradiotherapy

27. Treatment of the primary tumor summery

28. Principles of m anagement of inguinal lymph nodes The presence of palpable inguinal lymph nodes is associated with about 43% nodal metastasis Remainder of lymph node enlargement is secondary to inflammation The cure rate of groin resection in limited positive nodal disease 80% Inguinal lymph node dissection is associated with post operative morbidity The dissection of microscopic disease produces less post operative complications than bulky nodal metastasis

29. Principles of management of inguinal lymph nodes The presence and extent of lymph node metastasis is the most important prognostic factor for survival in penile cancer The goal of management for non palpable lymph nodes (N0) is to detect the presence metastasis with minimal morbidity N0 patients with no adverse features in the primary tumor for inguinal metastasis are placed under observation Those with adverse features in the primary tumor should undergo a staging procedure

30. Principles of management of inguinal lymph nodes The staging procedures for the groin are dynamic sentinel lymph node biopsy and superficial inguinal lymph node dissection The goal of management for palpable and resectable inguinal disease (N1-2) is eradication the disease Surgical resection of inguinal disease is achieved by standard inguinal lymph node dissection This procedure is associated with very significant morbidity

31. Management of non palpable inguinal lymph nodes (N0) N0 disease with low stage and low grade primary tumor (CIS, Ta and T1aG1) have very low incidence positive nodes (0 to 16%) The optimal management for this group is observation Pathological stage T1G2 in primary tumor is considered intermediate for occult inguinal metastasis Surveillance can be offered as an alternative to surgical staging in patients willing to comply with strict follow up Nonpalpable (cN0) nodes at high risk of occult metastasis (≥ T1b) are managed by surgical staging

32. Management of non palpable inguinal lymph nodes (N0) Surgical staging of inguinal lymph nodes is done by superficial inguinal lymph node dissection This is the most reliable staging procedure but is associated with a high morbidity Dynamic sentinel lymph node biopsy (DSNB) has high diagnostic accuracy but low morbidity This minimally invasive diagnostic procedure is used in high volume centers to reduce morbidity of surgical staging

33. Management of palpable and mobile inguinal lymph node (N1-2) disease The management of regional lymph nodes in penile cancer is decisive for survival Open radical inguinal lymph node dissection (ILND) is the standard of care for cN1-2 disease (including positive DSNB) If nodes are positive on frozen section in superficial dissection the complete dissection is performed Radical ILND has significant morbidity due to impaired lymph node drainage from the legs and scrotum

34. Features for standard inguinal lymph node dissection compared to modified dissection Has longer skin incision Greater saphenous vein is sacrificed Sartorius muscle transposition Removal of all nodes lateral to the femoral vessels and also deep nodes within the femoral triangle Thinner skin flaps

35. Landmarks for standard inguinal lymph node dissection A vertical line is drawn from the anterior superior iliac tubercle of about 15 cm inferiorly on the lateral aspect of the thigh Another second vertical line parallel to the first of about 9 cm is drawn from the pubic tubercle inferiorly on the medial aspect of the thigh An incision is made 2 cm below and parallel to the inguinal ligament from the first to the second line The skin flaps are the reflected cranially and caudally

36. Complications of inguinal lymph node dissection Hemorrhage Lymphocele Pulmonary embolism Wound infection Flap necrosis Lymphedema of scrotum and lower limbs Hypoalbuminemia

37. Superficial and modified complete inguinal dissection Superficial inguinal lymph node dissection involves removal of the nodes superficial to the fascia lata If nodes are positive on frozen section the complete ilioinguinal dissection is performed which has highest morbidity A complete modified inguinal dissection has a smaller incision, limited field of inguinal dissection, preservation of saphenous vein and thicker skin flaps This technique involves removal of deep nodes within the fossa ovalis but does not involve sartorius muscle transposition

38. Prophylactic pelvic lymph node dissection Prophylactic pelvic lymph node dissection in most cases is a staging procedure but in few patients it may have a therapeutic benefit It identifies candidates for early adjuvant therapy The presence of ≥ 3 positive inguinal lymph nodes on one side or extra nodal disease on histology is associated with positive ipsilateral pelvic lymph node disease The complete surgical inguinal and pelvic lymph node management should be completed within 3 months of diagnosis

39. Management of palpable and fixed lymph node (N3) disease Fixed inguinal nodal mass (i.e. fixed to the skin or underlying structures) or presence of pelvic lymphadenopathy is cN3 N3 disease amenable to surgery is first treated with neo-adjuvant chemotherapy using cisplatin or taxane based combination Responders to chemotherapy are then subjected to surgery Upfront surgery in N3 disease even when feasible is associated with significant complications which may delay or prevents chemotherapy Responders to chemotherapy/surgery have a 50% 5 year survival

40. Role of neoadjuvant and adjuvant chemotherapy in lymph node management Neoadjuvant chemotherapy is suitable for cN3 disease (i.e. pelvic and/or extensive/fixed inguinal lymph nodes) It is also appropriate for bulky cN2 (i.e. bulky bilateral mobile nodes) In non responders the potential benefits for surgery should be reevaluated as the prognosis is poor There is no strong evidence that supports the use of adjuvant therapy after resection of the primary tumor and lymph node dissection For healthy patients at very high risk of recurrence adjuvant chemotherapy can still be given after discussion of risks and benefits

41. Role of radiotherapy in lymph node management The use of primary (definitive) and adjuvant radiotherapy for node positive penile cancer remains controversial There is no level 1 evidence that supports its use Radiotherapy is being used for management of penile SCC in some institutions base on the experience of SCC in other body sites (Head/neck or vulvar)

42. Palliative treatment of penile cancer Low level evidence supports the use of platinum based combination chemotherapy as the preferred first line palliative systemic therapy Choices include triplet regimens (docetaxel/cisplatin/5FU, paclitaxel/ifosfamide/cisplatin) Duplet regimens (cisplatin/5FU, paclitaxel/carboplatin) Effective second line palliative chemotherapy regimens are lacking Those that were effective were associated with the median overall survival of < 6 months Radiotherapy is frequently used for the palliation of ulcerative fixed lymph nodes or dermal lymphatic spread

43. Follow up for penile cancer

44. Quality of life and patient support Penile cancer has significant impact on the quality of life The management of this disease requires a holistic and multidisciplinary approach In addition to definitive therapy of the cancer, psychological support, counselling and psychosexual therapy are key in the management of penile cancer Patients undergoing lymph node dissection requires lymphedema specialist services for assessment and management before significant lymphedema occurs

45. References Lous R. Kavoussi , Andrew C. Novick, Alan W. Partin, Craig A. Peters, CAMPBELL-WALSH Urology , 12 th Edition, Chapter 79, Elsevier Saunders, USA. European Association of Urology, 2024 updated guidelines, limited edition