Kevin R. Loughlin, MD, MBA
Kevin R. Loughlin, MD, MBA
Penile cancer occurs rarely in the United States and Western Europe. In the United States, the incidence is 1 to 2 cases for every 100,000 individuals a year. In Western Europe, it is less than 1% of all male cancers. Risk factors include being uncircumcised, poor hygiene, history of human papillomavirus (HPV) infection, and smoking tobacco. HPV strains 16 and 18, in particular, put men at risk for penile cancer.
The presentation of penile cancer is variable. Patients may present with a penile mass or ulcer. In addition, some patients develop a red, velvety rash or foul-smelling discharge from beneath the foreskin.
Clinicians should have a low threshold to biopsy penile lesions. This can usually be done under local anesthesia. No treatment should be undertaken without a confirmation of an unequivocal permanent section pathology diagnosis. Urologists should not depend on a frozen section diagnosis done at the same time as a partial or total penectomy.
Challenges in Penile Tumor Staging
It is important to stage the primary tumor (T), the regional lymph nodes (N), and the presence of distant metastases (M). Several staging systems have been used through the years, but currently, the TNM system is the most widely used.1
The grade of the primary lesion is also considered in determining prognosis (Table 1
Table 1. Stages and Grades of Penile Cancer1
Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice for the primary lesion.2
MRI is superior to computed tomography (CT) scans in the evaluation of the primary lesion because MRI has excellent soft tissue and spatial resolution. T2-weighted and gadolinium-enhanced T1-weighted images are the most useful in determining the local extent of the penile cancer.2
Determining lymph node status also is critical in establishing prognosis. Ravi reported that the 5-year survival rate declined from 95% for patients without nodal disease to 81% for patients with 1 to 3 positive nodes to 50% for patients with 4 or more positive nodes. CT, MRI, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and CT have all been used for the evaluation of inguinal lymph nodes.3
Ultrasound with fine needle aspiration cytology (FNAC) can be useful when there are palpable nodes on physical exam. The European Association of Urology supports the use of FNAC in this circumstance, noting sensitivity of 93%.4
CT imaging has been disappointing for the evaluation of inguinal lymph nodes. Horenblas et al reported a series of 14 patients and found that CT had a sensitivity of 36% and a specificity of 100%, but was unable to detect occult metastases in groins without palpable nodes.5
MRI results in evaluation of inguinal nodes have not been superior to CT.6
Due to the limitations of standard CT and MRI imaging of the inguinal nodes, FDG PET/CT has gained increasing acceptance as the study of choice for inguinal node imaging. Schlenker et al reported a prospective study of 35 patients with penile cancer and found that the FDG PET/CT had a sensitivity of 88.2% and a specificity of 98.1%, with a positive predictive value of 93.8% and a negative predictive value of 96.3%.7
Graafland et al also utilized FDG PET/CT for penile cancer staging and reported a sensitivity of 91%, a specificity of 100%, and a diagnostic accuracy of 96% in identifying inguinal/pelvic node involvement.8
The technique of sentinel node biopsy was introduced by Cabanas in 1977 in an attempt to sample the first landing site of inguinal node metastatic spread.9
His rationale was that this node or cluster of nodes located around the superficial epigastric vein was predictive of the status of the remainder of the inguinal nodes. However, the lymphatic drainage of the penis is variable and several authors have reported false negative rates of 10% to 25%.10-12
Therefore, this technique, although theoretically attractive, has fallen into disfavor.
To try to improve accuracy, dynamic sentinel lymph node biopsy (DSLNB) was introduced. This technique involves mapping the penile lymphatic drainage with blue dyes and/ or radiotracers.13
The results of DSLNB appear to be highly variable and user dependent; some results were no better than standard lymph node biopsy.14,15
Newer techniques, such as single-photon emission computed tomography (SPECT)/CT have been evaluated in a few centers with encouraging results.16
In a series of 84 patients, plain lymphoscintigraphy identified sentinel lymph nodes in 87% of patients whereas SPECT/CT was able to identify at least 1 node in 100% of patients. However, Jakobsen et al reported a series of 129 patients where the results of SPECT/CT and standard lymphoscintigraphy were essentially equivalent.17
Imaging of the inguinal nodes in penile cancer continues to evolve. However, at the present time, FDG PET/CT is gaining increasing acceptance as the imaging modality of choice.
Management of the Penile Lesion
Carcinoma in situ and verrucous carcinoma of the penis involve the superficial layers of the skin and can usually be treated topically with laser therapy, Mohs surgery, fluorouracil, imiquimod, or cryotherapy.18
This article will discuss primary stage II lesions that are best treated by either partial or total penectomy. The goals of therapy should be 2-fold: oncological cure and preservation of sexual function, when possible.19
The primary consideration of surgical planning for the urologist should be to achieve a clear surgical margin. For many years, the traditional dogma had been that a 2-cm margin was required to ensure cure; however, we reviewed our own series and found that all clear surgical margins were equivalent in terms of local control. This has practical implications in the management of the local lesion. A partial penectomy that does not provide enough phallic length for sexual stimulation and/or penetration and that does not afford the patient the ability to stand to void does not benefit the patient. A clear margin that enables sexual pleasure, even without penetration, and maintains the ability for the patient to stand to void is a desirable outcome.
Before either a partial or total penectomy is performed, a permanent pathologic biopsy should always be obtained. Proceeding with definitive extirpative surgery on the basis of a frozen section result represents an unnecessary risk that could result in unindicated disfiguring surgery. However, a frozen section should always be taken at the time of a partial penectomy to confirm a negative margin.20
A potential complication of either a partial or total penectomy is stenosis or stricture of the neomeatus. We have published the “rosebud” technique that is based on similar surgical principles utilized in the maturation of an ileal conduit stoma.21
The technique involves mobilization of the urethral stump after the completion of either a partial or total penectomy, which should provide a length of urethra of about 1 cm that can then be spatulated (Figures 1
A total penectomy is preferable in larger or more proximal penile lesions when a partial penectomy would not reliably provide a clear surgical margin. The base of the penis is circumscribed and the corpora cavernosa and corpus spongiosum are dissected proximally. The base of the corpora cavernosa is controlled with mattress sutures, and the urethra is mobilized with attention to preserving its vascularity. A useful technical point is to place an infant feeding tube into the remaining urethral stump and secure it with a suture. The feeding tube can then be grasped with a forceps, which facilitates passage down to the perineum where a neomeatus is created.
Figure 1. Urethral Mobilization for Creation of a Neomeatus21
Figure 2. Maturation of the Urethral Stump for Creation of a Neomeatus21
Management of the Inguinal Nodes
The surgical management of the inguinal nodes has evolved. For many years, it was accepted practice to give patients with palpable inguinal nodes a 6-week course of antibiotics to see if the enlarged nodes would resolve before proceeding with a lymphadenectomy. Today, most surgeons proceed with the groin dissection without a course of antibiotics unless the primary lesion is grossly infected.
The management of nonpalpable nodes has also evolved. With more accurate imaging studies, most clinicians proceed with an inguinal dissection if there is radiographic suspicion of metastases. In addition, Tabatabaei has provided useful information regarding the risk of nodal metastases based on the stage and grade of the primary tumor (Table 2
The classic open lymphadenectomy is associated with significant morbidity including lower extremity lymphedema, lymphoceles, wound infection, and wound separation. The limits of the dissection are the apex of the femoral triangle distally, the sartorius muscle laterally, the adductor longus medially, and the inguinal ligament superiorally.
Table 2. Positive Node Rate Based on Primary Tumor Stage and Grade22
In an attempt to decrease the morbidity of the surgery, Colberg introduced the concept of a modified inguinal lymphadenectomy.23
This technique is used primarily in nonpalpable disease or minimally palpable disease. This technique differs from the standard technique by (1) decreasing the extent of the node dissection by excluding the regions lateral to the femoral artery and caudal to the fossa ovalis, (2) saphenous vein preservation, (3) elimination of transfer of the sartorius muscle, and (4) preservation of the subcutaneous tissue superficial to Scarpa’s fascia. Regardless of whether a standard or modified lymphadenectomy is performed, careful handling of the skin edges is important to avoid postoperative wound complications. We have found the use of the Scott ring retractor useful to achieve this goal.24,25
Modifications of surgical technique continue to be reported. Endoscopic inguinal node dissections (the VEIL procedure) are now being performed with reports of longterm efficacy.26
In addition there is a growing experience with robotic inguinal lymphadenectomy that suggests comparable results to the traditional open dissection.27
The potential future advances in the management of penile cancer are exciting. Biomarkers may enable us to diagnose and monitor patients more accurately.28
There are also realistic options to replace the penis with either autologous tissue or with a penile transplant.29-31
The next decade will undoubtedly provide clinicians with new challenges and opportunities for the treatment of patients with penile cancer.
- TNM Staging System. Cancer.net website. Penile cancer: stages and grades. cancer.net/cancer-types/penile-cancer/stages-and-grades. Updated August 2017. Accessed May 1, 2018.
- Suh Ch, Bahefi AD, Tirumani SH, et al. Multimodality imaging of penile cancer: what radiologists need to know. Abdom Imaging. 2015;40(2):424-435. doi: 10.1007/ s00261-014-0218-6.
- Ravi R. Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol. 1993;72:817-819.
- Hakenberg OW, Compérat EM, Minhas S, et al. EAU guidelines on penile cancer: 2014 update. Eur Urol. 2015;67(1):142-150. doi: 10.1016/j.eururo.2014.10.017.
- Horenblas, van Tinteren H, Delamarre JF, et al. Squamous cell carcinoma of the penis: accuracy of tumor, nodes and metastasis classification system, and rate of lymphangiography, computerized tomography scan and fine needle aspiration cytology. J Urol. 1991;146(5):1279-1283. doi: 10.1016/S0022-5347(17)38068-0.
- Heyns CF, Fleshner N, Sanger V, et al. Management of lymph nodes in penile cancer. Urology. 2010;76(2 suppl 1):S43-57. doi: 10.1016/j.urology.2010.03.001.
- Schlenker B, Scher B, Tilling R, et al. Detection of inguinal lymph node involvement in penile squamous cell carcinoma by 18F-fluorodeoxyglucose PET/CT: a prospective single-center study. Urol Oncol. 2012;30(1):55-59. doi: 10.1016/j.urolonc.2009.10.012.
- Graafland NM, Leijte JA, Valdes Olmas RA, et al. Scanning with 18F-FDG-PET/CT for detection of pelvic nodal involvement in inguinal node-positive carcinoma. Eur Urol. 2009;56(2):339-345. doi: 10.1016/j.eururo.2009.05.016.
- Cabanas RM. An approach for the treatment of penile carcinoma. Cancer. 1977;39(2):456-466.
- Fossa SD et al. Cancer of the penis. Experience at Norwegian Radium Hospital 1974-1985. Eur Urol. 1987;13(6):372-377.
- Cabanas RM. Anatomy and biopsy of sentinel lymph nodes. Urol Clin North Am. 1992;19(2):267-276.
- Pettaway CA, Pisters LL, Dinney CP, et al. Sentinel lymph node dissection for penile carcinoma: the M.D. Anderson Cancer Center experience. J Urol. 1995;154(6):1999- 2003. doi: 10.1016/S0022-5347(01)66671-0.
- Wespes E. The management of regional lymph nodes in patients with penile carcinoma and reliability of sentinel node biopsy. Eur Urol. 2007;52(1):15-16. doi: 10.1016/j.eururo.2007.02.045.
- Speiss PE, Izawa JI, Bassett R, et al. Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging penile cancer: results with pathologic correlation. J Urol. 2007;177(6):2157-2161. doi: 10.1016/j.juro.2007.01.125.
- Sadeghi R, Gholami H, Zakavi SR, et al. Accuracy of sentinel lymph node biopsy after inguinal lymph node staging of penile squamous cell carcinoma: systematic review and metaanalysis of the literature. J Urol. 2012;187(1):25-31. doi: 10.1016/j.juro.2011.09.058.
- Brouwer OR, van den Berg NS, Mathéron HM, et al. A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. Eur Urol. 2014;65(3):600-609. doi: 10.1016/j.eururo.2013.11.014.
- Jakobsen JK et al. DaPeCa-3: promising results of sentinel node biopsy combined with (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in clinically lymph node-negative patients with penile cancer - a national study from Denmark. BJU Int. 2016;118(1):102-111. doi: 10.1111/bju.13243.
- Treatment options for penile cancer, by stage. American Cancer Society website. cancer.org/cancer/penile-cancer/treating/by-stage.html. Accessed May 1, 2018.
- Loughlin KR. Penile cancer sparing surgery: the balance between oncological cure and functional preservation. Urol Oncol. 2018;36(4):153-155. doi: 10.1016/j. urolonc.2017.12.008.
- Hoffman MA, Renshaw AA, Loughlin KR. Squamous cell carcinoma of the penis and microscopic pathologic margins: how much margin is needed for local cure? Cancer. 1999;85(7):1565-1568.
- Loughlin KR. The “rosebud” technique for creation of a neomeatus after partial or total penectomy. Br J Urol. 1995;76(1):123-124.
- Tabatabaei S, McDougal WS. Positive node pathology based on primary tumor stage and grade. In: Richie JP, D’Amico AV, eds. Urologic Oncology. Philadelphia, PA: Elsevier/Sanders; 2005:710-722.
- Colberg JW, Andriole GL, Catalona WJ. Long-term follow-up of men undergoing modified inguinal lymphadenectomy for carcinoma of the penis. Br J Urol. 1997;79(1):54-57.
- Loughlin KR. Use of Scott ring surgical retractor for inguinal node dissection. Br J Urol. 1988;61(4):367.
- Loughlin KR. Surgical management of penile carcinoma: the inguinal nodes. BJU Int. 2006;97(5):1125-1134. doi: 10.1111/j.1464-410X.2006.06178.x.
- Tobias-Machado M, Tavares A, Molina WR Jr. et al. Video endoscopic inguinal lymphadenectomy (VEIL): minimally invasive resection of inguinal lymph nodes. Int Braz J Urol. 2006;32(3):316-321.
- Singh A, Jaipuria J, Goel A. Comparing outcomes of robotic and open inguinal lymph node dissection in patients with cancer of the penis. J Urol. 2018;199(6):1518- 1525. doi: 10.1016/j.juro.2017.12.061.
- Vuichoud C, Klap J, Loughlin KR. The emerging role and promise of biomarkers in penile cancer. Urol Clin North Am. 2016;43(1):135-143. doi: 10.1016/j. ucl.2015.08.012.
- Capelouto CC, Orgill DP, Loughlin KR. Complete phalloplasty with prelaminated osteocutaneous fibula flap. J Urol. 1997;158(6):2238-2239. doi: 10.1016/S0022-5347(01)68213-2.
- Bateman C. World’s first successful penis transplant at Tygerberg Hospital. S Afr Med J. 2015;105(4):251-252. doi: 10.7196/SAMJ.9602.
- Thoma C. Surgery: first penis transplant in the USA. Nat Rev Urol. 2017;14(8):452. doi: 10.1038/nrurol.2017.88. doi: 10.1038/nrurol.2017.88.