Penile cancer evaluation includes (at presentation) a painless mass/ulcer, with a foul odor and discharge, located on the glans (48%), foreskin (21%), glans and prepuce (9%), coronal sulcus (6%), and shaft (<2%). Delays in diagnosis are not uncommon with a median delay of 6 months. When evaluating these patients, it is important to not just do a physical examination of the penis, but also the inguinal lymph nodes. A penile biopsy establishes diagnosis, grade and T-stage, with an excisional biopsy the most reliable, but a punch biopsy also feasible for assessing depth. Imaging modalities may include an MRI of the penis, and an MRI, CT, or PET/CT scan for evaluating the inguinal lymph nodes. The TNM staging for penile cancer is as follows:
The main risk factors for penile cancer include phimosis (OR for diagnosis 11-16 versus no phimosis), and HPV infection/condyloma acuminate (22.4% in verrucous squamous cell carcinoma, 36-66% in basaloid-warty squamous cell carcinoma). HPV DNA is detectable in approximately 50% of all penile cancer, with the most common types being HPV 16, 18, and 6/11. Precursor cancerous penile lesions are rare, with 60-100% of PeIN lesions HPV DNA positive. The natural history of penile cancer is as follows: primary penile lesion dissemination (lymphatics to regional lymph nodes, +/ hematogenous spread) metastases (lungs, liver, bone, brain) death due to regional complications.
Data from the Brazilian state of Maranhão (the region with the highest incidence of penile cancer worldwide) suggests that among 116 penile cancer interviewed, the majority of patients lived in a rural area (57%), worked in farming (58%), had a low level of schooling or no schooling (90%), and were married or in a stable relationship (74%) . Phimosis (66%), poor/moderate genital hygiene (73%), history of sexually transmitted infections (55%), and zoophilia (60%) were found in the majority of patients. The most common initial symptom was pruritus (37%), and most patients waited to seek treatment (mean time to treatment, 18.9 months; range, 2-84 months). HPV-related histologies were observed in 62% of patients, and most patients had histological grades II or III (87%), stage ≥T2 disease (84%), and lymphadenopathy at admission (42%). A penectomy was performed in 96% of patients.
Dr. Rodriguez notes that for penile cancer, the presence and extent of lymph metastasis dictates survival. The 5-year survival rate for patients with negative inguinal lymph nodes is 85%, 29-40% for those with positive inguinal lymph nodes, and 0-10% for those with positive pelvic lymph nodes. Complications from open inguinal lymph node dissection traditionally range from 50-90%, most commonly lymphedema, skin necrosis, lymphocele, wound dehiscence, and wound infection. Several strategies to minimize morbidity have developed, such as dynamic sentinel node biopsy, superficial/fascial sparing dissections, and laparoscopic/robotic lymphadenectomy. In an eUROGEN survey of penile cancer surgeon’s utilization of dynamic sentinel lymph node biopsy and radical inguinal lymph node dissection , they found that 57% of surgeons perform >10 inguinal lymph node dissections per year and 86% offer dynamic sentinel lymph node biopsy. However, there was variation in management with regards to dye injection site, use of lymphoscintigraphy, preferred incision sites, techniques for lymphatic control, duration of empiric antibiotic therapy, perioperative thromboprophylaxis, time points for drain remove, and definition of the inguinal lymph node dissection floor.
There are several controversies in penile cancer that Dr. Rodriguez discussed:
- Not all penile cancers are associated with HPV – what is the role of HPV vaccination in males? The quadrivalent HPV vaccine covers HPV 6, 11, 16, and 18, and the nine-valent vaccine covers 6, 11, 16, 18, 31, 33, 45, 52, and 58.
- Should high-risk HPV status be added to further improve the prognostic stratification of patients? Could this prognostic stratification be used to guide inclusion criteria in adjuvant therapy trials? In a subgroup of pN2-N3 patients stratified by high-risk HPV status, those that were positive had worse survival:
Additionally, HPV positivity has been associated with lower nodal stage and independently better outcome after radiotherapy. Dr. Rodriguez notes that there are several challenges to promote: (i) neonatal circumcision, (ii) tobacco cessation, (iii) proper genital hygiene, (iv) early detection of a suspected lesion, and (v) educational campaigns to inform the public of prevention: HPV and other sexually transmitted diseases through vaccination and use of condoms.
Dr. Rodriguez concluded his presentation with the following summary points:
- There is a need for educational campaigns with respect to prevention and early detection
- We need to identify referral centers of excellence in a region to support ongoing and future clinical trials such as the International Penile Advanced Cancer Trial (InPACT, NCT2305654)
- We need a multidisciplinary approach to this disease, including the pathologist, medical oncologist, and radiation oncologist
- There is a need for a unique global database of cases detected and treated with inclusion of specific clinical and pathological outcomes, including assessment of HPV status, squamous cell subtype, surgical margins (including width), and incorporation of radiomics and liquid biopsies
Presented by: Alejandro R. Rodriguez, MD, Secretary-General of the CAU, Rochester General Hospital, Rochester, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.
- Vieira CB, Feitoza L, Pinho J, et al. Profile of patients with penile cancer in the region with the highest worldwide incidence. Sci Rep. 2020 Feb 19;10(1):2965.
- Fankhauser CD, Ayres BE, Issa A, et al. Practice Patterns Among Penile Cancer Surgeons Performing Dynamic Sentinel Lymph Node Biopsy and Radical Inguinal Lymph Node Dissection in Men with Penile Cancer: A eUROGEN Survey. Eur Urol Open Sci 2021;24:39-42.
- Wang B, Gu W, Wan F, et al. Prognosis of the 8th TNM Staging System for Penile Cancer and Refinement of Prognostication by Incorporating High Risk Human Papillomavirus Status. J Urol. 2020 Mar;203(3):562-569.