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Year : 2020  |  Volume : 36  |  Issue : 1  |  Page : 8-15

Management of clinically node-negative groin in patients with penile cancer

Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission23-Jul-2019
Date of Acceptance02-Nov-2019
Date of Web Publication2-Jan-2020

Correspondence Address:
Gagan Prakash
Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/iju.IJU_221_19

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Malignant penile neoplasms are commonly squamous etiology, with the inguinal nodes being the first echelon of spread. The disease spreads to the pelvic lymph nodes only after metastases to the groin nodes, and this is the most important prognostic factor in penile carcinoma. While treatment of penile carcinoma with proven metastases to the inguinal lymph nodes mandates ilioinguinal lymph node dissection, the treatment of patients with impalpable nodes is more controversial. Overtreatment leads to excessive treatment-related morbidity in these patients, while a wait-and-see policy runs the risk of patients presenting with inguinal and distant metastases, which would have been curable at presentation. Unfortunately, no single imaging modality has been proved to be convincingly superior in the staging, and hence, management of the clinically negative groin has been subject to debate. While some high volume centers have promoted the use of dynamic sentinel lymph node biopsy, others advocate the use of the modified inguinal lymph node template to stage the groin adequately. Newer techniques such as video endoscopic inguinal lymph node dissection have been introduced as an alternative to the original radical inguinal lymphadenectomy to reduce morbidity.

How to cite this article:
Niyogi D, Noronha J, Pal M, Bakshi G, Prakash G. Management of clinically node-negative groin in patients with penile cancer. Indian J Urol 2020;36:8-15

How to cite this URL:
Niyogi D, Noronha J, Pal M, Bakshi G, Prakash G. Management of clinically node-negative groin in patients with penile cancer. Indian J Urol [serial online] 2020 [cited 2023 Mar 21];36:8-15. Available from:

   Introduction Top

Penile cancer is an important health problem in India. The age-adjusted incidence of penile cancer in urban India is 0.7–2.3/100,000 individuals, whereas in rural India, it reaches up to 3/100,000.[1] The most common histological type is squamous cell carcinoma. Other histopathologic types described include verrucous, papillary, squamous, warty, and basaloid.[2] Other histologies include basal cell carcinoma, Paget's disease, leiomyosarcoma, and melanoma.[3]

Lymph node metastasis is the most important prognostic indicator for survival in squamous cell carcinoma of the penis.[4] Patients with low-stage disease, a clinically N0 groin [Table 1], can achieve a 5-year survival of almost 80% with adequate treatment. However, survival declines precipitously as the lymph node burden increases, with a 5-year survival of 0%–17% in patients with N3 disease.[5] A thorough lymphadenectomy in penile cancer offers a chance for cure in low nodal burden disease in contrast to other urological malignancies such as bladder cancer or renal cell carcinoma, where nodal involvement portends poor prognosis and clearance has debatable therapeutic benefit.[6] Meticulous dissection of the groin nodes is important not only for eliminating the disease, but also for appropriate staging, prognostication, and guiding adjuvant treatment.
Table 1: Definition of clinically N0 groin

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A radical inguinal dissection is prone to an array of surgical complications. Hence, there is a need to achieve optimal staging, and thereby offer optimum local disease control while avoiding unnecessary groin morbidity. This has been an area of interest and debate in the management of the clinically N0 groin in penile cancer.

   Incidence of Clinically N0 Groin Top

Diagnosis and treatment of penile cancer in India is often delayed due to associated psychosocial aspects, with a large majority of patients presenting with bulky nodal disease. In world literature, only 20% of patients with penile cancer present with palpable inguinal nodes.[7] This number is as high as 20%–96% in the Indian population.[1] However, in recent years, there is a trend toward a greater proportion of men presenting with clinically impalpable inguinal lymph nodes even in India. Increased awareness and early referrals/better access to health care could be responsible for this change.

   Oncologic Implication of Addressing N0 Groin Top

The surgeon performs a lymphadenectomy in an N0 groin to provide a precise pathological stage, and thereby guide further treatment as well as to clear microscopic disease, when present. A retrospective series from India found that patients with poor compliance to follow up have improved cancer-specific survival if they undergo an early interval inguinal lymph node dissection (ILND) (at the same admission or within 2 months) when compared to patients undergoing a delayed lymph node dissection (91% vs. 13%, P = 0.007).[8] The patients undergoing delayed ILND also had a significantly higher rate of extracapsular extension. Studies from other parts of the world have shown improved survival for patients who underwent early ILND compared to patients undergoing delayed ILND for lymph node metastases detected during surveillance.[9],[10]

   Role of Imaging Top

Clinical examination alone may miss 20%–25% of pathological positive inguinal nodes.[7] Ultrasound (USG) combined with fine-needle aspiration cytology (FNAC) of morphologically suspicious-looking nodes is a useful adjunct to clinical examination, especially in obese and previously irradiated patients with a sensitivity and specificity of 39% and 100%, respectively.[11] However, false-negative rates of FNAC reach up to 15%.[7] Therefore, if clinical suspicion of node positivity is high, and if FNAC is negative, a repeat FNAC or an excision biopsy should be considered. Computed tomography (CT) and magnetic resonance imaging of the abdomen and pelvis have not been found to detect micrometastases reliably and are currently not recommended routinely.[12]

The role of fluorodeoxyglucose-positron emission tomography (PET)/CT in penile cancer was first reported in 2005 by Scher et al. Although an initial study showed a sensitivity of 89% and a specificity of 100% for PET scanning, a later study in clinically node-negative penile carcinoma found a low sensitivity, especially in the lymph nodes <10 mm.[13],[14] At present, routine imaging with any modality mentioned above is not recommended as per prevailing guidelines but may be employed in certain situations such as obese patients and previously irradiated patients to help in preoperative staging and treatment planning.

   Role of Prophylactic Antibiotics Top

Older series have reported that patients with penile cancer harbor infection in a large proportion, as high as 30%–50%.[15] This formed the basis for treating enlarged nodes with prophylactic antibiotics before evaluation. This practice has been given up in the absence of clinically apparent infection because more recent series have reported metastatic involvement in almost 70% of clinically enlarged nodes.[16]

   Risk Stratification of Penile Cancer Top

About 20%–25% of patients harbor occult metastatic disease despite having clinically impalpable inguinal nodes.[17] This number is higher among patients with high-grade disease and with lymphovascular invasion (LVI).[5] In such patients, a thorough inguinal lymphadenectomy offers a chance for cure.

A nonrandomized study of forty patients with T2, T3 penile carcinoma demonstrated a survival benefit in patients undergoing a prophylactic inguinal lymphadenectomy with positive inguinal lymph node metastases as compared to patients who underwent a therapeutic lymphadenectomy for inguinal recurrences detected during close follow-up (3 years cancer specific survival 84% vs. 35%, P = 0.0017).[9] On the other hand, radically addressing cN0 groins has its drawbacks. Even in high-volume centers, radical inguinal lymphadenectomy leads to postoperative complication rates between 42% and 57%.[18] Some of these complications, such as wound necrosis and venous thromboembolism, warrant additional surgical procedures and can be particularly debilitating while also delaying adjuvant treatment. Hence, there is a need to find a balance between the aggressive treatment of the cN0 groins and observation. This gave rise to the concept of risk stratification of penile carcinoma.

In a prospective study with 100 patients managed according to the European Association of Urology (EAU) risk stratification [Table 2], after a median follow-up of 29 months, all the patients who were categorized as low risk remained disease-free. However, in 82% of the patients categorized as high risk, the invasive nodal staging was negative for metastasis;,[7] i.e., to pick up 20% of clinically occult nodal metastases, 80% of patients will have to undergo invasive inguinal staging despite having negative nodes. However, given the fact that adequate inguinal staging and clearance can be curative in carcinoma of the penis, this is a caveat that needs to be accepted till more accurate means of inguinal staging can be formulated.
Table 2: The European Association of Urology risk stratification with chances of lymph node metastases

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Nomograms for predicting lymph node involvement have been formulated using tumor characteristics such as tumor thickness, growth pattern, grade, LVI, T stage, and cN stage. The nomogram proposed by Ficarra et al. showed a good concordance index of 0.876, but a lack of validation in other cohorts precludes its use in daily clinical practice.[19][Figure 1] lists the management schema as per the EUA and NCCN guidelines.
Figure 1: Schema of management of cN0 Groin as per recent guidelin

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   Human Papillomavirus and Molecular Markers in the Cn0 Groin Top

Squamous cell carcinoma of the penis, as reported in Western literature, is associated with human papillomavirus (HPV) infection in up to 50% of the cases.[20],[21] The better prognosis in HPV associated head-and-neck cancers has laid the basis for the de-escalation of therapy in this subset.[22] However, studies in penile cancer failed to show an association between HPV infection and lymph node metastases and 10-year survival rates.[23] HPV-associated penile cancers show extensive levels of tumor-infiltrating lymphocytes (TIL). In addition, programmed death ligand-1 was expressed in high-risk HPV-negative tumors, and the pattern of expression affected lymph node metastases and survival.[24] This is being investigated as a potential area for TIL-based immunotherapy and treatment de-escalation in penile carcinoma as well.[25] In the era of personalized cancer care, molecular profiling of penile cancers may potentially identify patients with occult inguinal disease more accurately, obviating the need for invasive inguinal staging and its associated morbidity.

   Lymphatic Drainage of the Penis Top

Lymphatic drainage of the penis encompasses a superficial system that drains the skin and a deeper system that drains the glans and corporal structures.[26] [Figure 2] summarizes the following aspects of penile lymphatic drainage:
Figure 2: Lymphatic drainage of the penis

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  1. The drainage of the penis is bilateral
  2. Rouviere divided the superficial lymphatic system into five zones concerning the saphenous vein draining into the femoral vein: superomedial (i), superolateral (ii), inferomedial (iii), inferolateral (iv), and central (v)[27]
  3. Lymphangiographic studies by Cabanas showed the superomedial group to be the first station of draining lymph nodes from the penis
  4. The deep inguinal lymphatic system is smaller in size, predominantly located medial to the femoral vessels, deep to the fascia lata. It includes the Cloquet's node located in the femoral canal, which is the gateway of spread to the pelvic nodes
  5. Metastases to pelvic nodes skipping the inguinal basin are only anecdotal and can possibly be attributed to inadequate sampling of the inguinal nodes.[28]

   Observation/surveillance of the Groin and Prophylactic Radiation Top

This strategy for the management of the cN0 groin is recommended only in the low-risk group (PTA, pT1a, and G1). Regional recurrences are most commonly seen in the first 2 years after treatment. The incidence is the highest in patients managed by surveillance (9%) as against those managed by invasive nodal staging or dynamic sentinel node biopsy (DSNB) and found to be pN0 (2.3%). The EAU guidelines suggest 3 monthly clinical examinations for the first 2 years, followed by 6 monthly clinical examinations until 5 years after treatment. Suspicious nodes on palpation must be subjected to FNAC with or without USG guidance. A clinically positive groin on surveillance should be subjected to a unilateral radical inguinal lymphadenectomy. The opposite side, even if clinically disease-free, should be subjected to a modified/superficial groin node dissection or a DSNB.[7]

Radiation therapy has historically been used prophylactically in the N0 groin. A nonrandomized trial from our institution more than two decades back showed a superior 5-year survival for a cN0 groin treated with ILND compared to a cN0 irradiated with 50 Gy to the inguinal-femoral region, 74% vs. 66%, leading it to fall out of favor in clinical practice.[29] With a better understanding of drainage pattern and evolution of radiotherapy techniques, this area could be revisited.

   Radical Inguinal Lymphadenectomy Top

The procedure involves clearing the superficial and deep inguinal nodal basins. Daseler's template is as follows: superiorly by a line joining the anterior superior iliac spine to the pubic tubercle, laterally a line 20 cm down perpendicular to the iliac spine, medially a line 15 cm down perpendicular to the pubic tubercle and inferiorly, a line joining these two points. It involves ligating the saphenous vein and baring the femoral vessels.[30] Median lymph node count in a radical inguinal dissection is 10–11.[31] However, radical lymphadenectomy is associated with major complications such as wound necrosis and deep vein thrombosis in up to 37.5% cases and minor complications such as surgical site infection, limb edema, and seromas in up to 54% of patients.[32] The morbidity of the procedure, especially in patients with low risk of harboring inguinal metastases, led surgeons to search for less invasive methods of staging the cN0 groin.

   Modified Inguinal Lymphadenectomy Top

To reduce the complications following radical inguinal nodal dissection while maintaining the accuracy of invasive inguinal nodal staging for a clinically N0 groin, a modified template was first proposed by Catalona in 1988.[33] The aim of this template was to remove the nodal stations with the highest probability of being involved (central and superior zones) while minimizing morbidity. No head-to-head randomized trials have been performed comparing radical dissection to the modified template in cN0 disease. According to the NCCN guidelines, frozen section examination of the modified template is recommended, with completion of the entire radical template if two or more positive nodes are found.[34]

A horizontal—4-5 cm incision parallel to the inguinal ligament is employed. Horizontal incisions are reported to be more in line with the pattern of blood supply and cause less flap necrosis when compared to the vertical or lazy-S incision.[5],[7] The template for Modified Inguinal Lymph node Dissection (MILD) is bounded medially by the lateral border of the adductor longus, laterally by the femoral artery, superiorly by the external oblique just above the spermatic cord, and inferiorly by the fascia lata just beyond the fossa ovalis. This template involves the preservation of the saphenous vein and does not include tissue lateral to the femoral artery or distal to the fossa ovalis.[7] The false-negative rate of MIL has been reported to be between 0% and 5.5%, while the morbidity has been reported to be between 10% and 36% making it a standard method of invasive inguinal staging.[34],[35],[36],[37],[38]

   Superficial Inguinal Lymphadenectomy Top

Superficial Inguinal Lymph node Dissection (SILD) is performed via a 6–8 cm horizontal incision 1 cm inferior to the inguinal fold. In comparison with the MILD, this procedure involves excision of all the nodal basins superficial to the fascia lata from the adductor longus medially to the sartorius laterally. Like the MILD, the long saphenous vein is preserved. A median lymph node count of 8–10 is achieved.[31] This packet too should be submitted for frozen section analysis, mandating completion if positive nodes are found. Intuitively, SILD has a higher lymph node yield compared to MILD. However, whether this translates into a lower false-negative rate or lower recurrence rate is not yet known.

   Dynamic Sentinel Node Biopsy Top

The concept of sentinel node biopsy in penile cancer was first introduced by Cabanas in 1977.[39] Lymphangiographic studies show nodes medial to the superficial epigastric vein as the first echelon draining the penis [Figure 3] and [Figure 4]. Involvement of these nodes was a harbinger of inguinal disease and mandated clearance. The concept of sentinel node biopsy was reexplored for melanoma in 1992 by Morton et al., who introduced a dynamic component using an injection of isosulfan or patent blue dye to identify individual drainage patterns.[40] In 2000, Horenblas et al. lay down the base for the current concept of DSNB in a series of 55 patients, individual mapping was done using Tc-99-labeled sulfur colloid a day before and patent blue on the day of surgery. A sensitivity of 80% was reported, but the high false-negative rates were a cause for concern.[41]
Figure 3: Dynamic sentinel lymph node biopsy – injection of dye

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Figure 4: Dynamic sentinel lymph node biopsy – identification of sentinel node

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Over the years, the same Netherlands Cancer Institute team has further refined the technique and has suggested the following protocol:[42]

  1. Intradermal injection of radiolabeled sulfur colloid on the day before surgery with lymphoscintigraphy
  2. USG-guided FNAC from palpably enlarged nodes that fail to pick up colloid activity
  3. Intradermal injection of patent blue dye just before surgery
  4. Using a gamma probe during surgery to identify “hot” nodes
  5. Intraoperative palpation of the inguinal region
  6. Excision of all “hot,” blue and palpable nodes for frozen section examination
  7. Exploration of groin when there is no activity on preoperative lymphoscintigram (4%–6%)
  8. Serial sectioning and immune-histochemical staining of the nodes instead of routine paraffin sections.

This procedure has proven to be a reliable inguinal staging modality with results comparable to those of DSNB in breast cancer and melanoma where it is standard of care.[7] A prospective multicenter study of 323 patients has shown DSNB to have an impressive sensitivity and specificity of 93% and 100%, respectively. The reported complication rate was <5%, and all complications were managed conservatively.[43] DSNB has a significant learning curve. In a single-center experience, the false-negative rate reduced from 19.2% in the 1994–2001 cohorts to an accep[Table 4].8% in the 2001–2004 cohorts. The complication rate similarly dropped from 10.2% to 5.7%.[44] Hence, DSNB is promoted only in centers with a large volume of experience performing the procedure.[35]

Recently, there is interest in the use of indocyanine green (ICG) labeled colloid for detection of sentinel nodes with a near-infrared fluorescence camera used to detect uptake. This technique, initially described by Brouwer et al., demonstrated a higher number of sentinel lymph nodes (SLNs) detected when ICG-99m Tc nanocolloid was compared to blue dye (96.8% vs. 55.7%; P <.0001).[45] It has been postulated that the easy and fast outflow of blue dye to the next nodal station compared to ICG's outflow led to the lower sensitivity of blue dye. Multiple studies have compared ICG with Tc-labeled radiocolloid and revealed improved SLN detection with ICG.[46],[47],[48] This improved optical SLN detection using ICG may subsequently lead to the blue dye being replaced. The additional advantages are low cost, elimination of radioactivity, and documented long-term safety. The disadvantage of ICG is poor penetrance through adipose tissue, requiring skin incision for identification in some obese patients. This technique is still investigational and not yet accepted as the standard of care.

   Minimally Invasive Techniques Top

The high incidence of surgical morbidity following inguinal node dissection deters a large proportion of patients from accepting the procedure. A SEER database analysis revealed that only 25% of all patients who should have received invasive inguinal staging actually receive it.[49] The advent of minimally invasive procedures in other specialties led to the inguinal lymphadenectomy being described using both laparoscopic and robotic approaches.

Video endoscopic inguinal lymphadenectomy (VEIL) was described and reported by Tobias-Machado et al. in 2008.[50] VEIL encompasses a laparoscopic performance of radical inguinal lymphadenectomy with the sacrifice of the great saphenous vein. This procedure showed similar lymph node yield and comparable oncological outcome to an open procedure at a median follow-up of 33 months.[51] The VEIL arm had significantly less morbidity (20% vs. 70%, P = 0.015) and reduced hospital stay (24 h vs. 6.4 days).

Sotelo et al. reported outcomes of the endoscopic ILND for penile carcinoma in 2009. This technique utilized the MILD template, preserving the saphenous vein and deep inguinal nodes were cleared only if frozen section analysis showed positive nodes. This technique too showed decreased surgical complications without affecting the oncologic outcome in their preliminary results.[52]

A Phase 1 study for robotic-assisted VEIL (RAVEIL) was reported by Matin et al. in 2013. After performing RAVEIL, a small incision was made to check the adequacy of clearance achieved. RAVEIL achieved adequate clearance with acceptable lymph node yield as compared to an open procedure. Due to the incision placed to check clearance, this study could not comment upon the difference in surgical morbidity.[53] A study from India reported long-term lymphedema in 4 out of the 22 patients with one recurrence (5.2%) in pathological N0 groin during follow-up.[54]

A more recent large study from India has confirmed oncological safety of Robotic assisted groin node dissection and found that the benefit compared to open is more pronounced for non bulky lymph node positive groins.[55] Given the dramatic decrease in surgical morbidity, equivalent nodal yield, and comparable short-term oncologic outcomes, these endoscopic procedures have been widely accepted. The complication rates between different procedures as described in the literature have been listed in [Table 3], while [Table 4] describes the benefits and drawbacks of each modality of staging the cN0 groin.
Table 3: Comparison of complication rates

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Table 4: Benefits and drawbacks of different staging modalities

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   Relevance of Changes in the Recent American Joint Committee on Cancer 8 Staging Top

  1. pT1 corresponds to disease in the subepithelial connective tissue. T1b disease includes cases with Grade 3 histology, presence of LVI, perineural invasion, or sarcomatoid histology. T1b disease has a higher chance of metastasis to lymph nodes (33.3%–50% in T1b vs. 10.5%–18.1% in T1a) and warrants invasive inguinal staging[56],[57]
  2. In American Joint Committee on Cancer 7, involvement of corpus spongiosum or cavernosa was staged as T2 and urethral involvement comprised T3 disease. It was observed that cavernosal involvement was associated with higher inguinal lymph node involvement as compared to corpus spongiosum alone (48.6%–52.5% vs. 33%–35.8%). Hence, involvement of corpus spongiosum alone is now categorized as pT2, and cavernosal involvement upstages the disease to pT3.[56],[58]

   Conclusion Top

As of today, all intermediate- and high-risk groups with cN0 groins should undergo invasive inguinal staging in the form of MILD/SILD, DSNB, or VEIL even if the FNAC shows no metastases. Those with positive nodes on frozen section analysis should undergo a complete clearance. Surveillance may be offered as an option only for low-risk groups amenable to regular follow-up.[34],[35] A lack of large randomized controlled trials, the heterogeneity of patient groups with cN0 groin, and lack of any meta-analysis have limited the formation of stringent guidelines. With many unanswered questions in the management of the cN0 groin [Table 5], there is a need for multicenter collaboration to provide Level 1 evidence-based guidelines for penile cancer patients with cN0 groin. Global initiatives like the InPACT study for locally advanced penile carcinomas are the way forward for answering questions for this rare cancer.[59] India should take the lead in initiating similar multicenter trials planned across high volume centers to determine the standard of care for addressing groins in penile cancer patients.
Table 5: Unanswered questions in the management of N0 groin

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The authors would like to thank Meher Luthra for her help with the figures.

Financial support and sponsorship:


Conflicts of interest:

There are no conflicts of interest.

   References Top

Misra S, Chaturvedi A, Misra NC. Penile carcinoma: A challenge for the developing world. Lancet Oncol 2004;5:240-7.  Back to cited text no. 1
Cubilla AL, Reuter V, Velazquez E, Piris A, Saito S, Young RH. Histologic classification of penile carcinoma and its relation to outcome in 61 patients with primary resection. Int J Surg Pathol 2001;9:111-20.  Back to cited text no. 2
Downes MR. Review of in situ and invasive penile squamous cell carcinoma and associated non-neoplastic dermatological conditions. J Clin Pathol 2015;68:333-40.  Back to cited text no. 3
Ficarra V, Akduman B, Bouchot O, Palou J, Tobias-Machado M. Prognostic factors in penile cancer. Urology 2010;76:S66-73.  Back to cited text no. 4
Leone A, Diorio GJ, Pettaway C, Master V, Spiess PE. Contemporary management of patients with penile cancer and lymph node metastasis. Nat Rev Urol 2017;14:335-47.  Back to cited text no. 5
Djajadiningrat RS, van Werkhoven E, Horenblas S. Prophylactic pelvic lymph node dissection in patients with penile cancer. J Urol 2015;193:1976-80.  Back to cited text no. 6
Horenblas S. Lymphadenectomy in penile cancer. Urol Clin North Am 2011;38:459-69, vi-vii.  Back to cited text no. 7
Gulia AK, Mandhani A, Muruganandham K, Kapoor R, Ansari MS, Srivastava A. Impact of delay in inguinal lymph node dissection in patients with carcinoma of penis. Indian J Cancer 2009;46:214-8.  Back to cited text no. 8
[PUBMED]  [Full text]  
Kroon BK, Horenblas S, Lont AP, Tanis PJ, Gallee MP, Nieweg OE. Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases. J Urol 2005;173:816-9.  Back to cited text no. 9
Johnson DE, Lo RK. Management of regional lymph nodes in penile carcinoma. Five-year results following therapeutic groin dissections. Urology 1984;24:308-11.  Back to cited text no. 10
Kroon BK, Horenblas S, Deurloo EE, Nieweg OE, Teertstra HJ. Ultrasonography-guided fine-needle aspiration cytology before sentinel node biopsy in patients with penile carcinoma. BJU Int 2005;95:517-21.  Back to cited text no. 11
Mueller-Lisse UG, Scher B, Scherr MK, Seitz M. Functional imaging in penile cancer: PET/computed tomography, MRI, and sentinel lymph node biopsy. Curr Opin Urol 2008;18:105-10.  Back to cited text no. 12
Scher B, Seitz M, Reiser M, Hungerhuber E, Hahn K, Tiling R, et al. 18F-FDG PET/CT for staging of penile cancer. J Nucl Med 2005;46:1460-5.  Back to cited text no. 13
Leijte JA, Graafland NM, Valdés Olmos RA, van Boven HH, Hoefnagel CA, Horenblas S. Prospective evaluation of hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography in staging clinically node-negative patients with penile carcinoma. BJU Int 2009;104:640-4.  Back to cited text no. 14
Virseda Rodríguez JA, Salinas Sánchez A, Hernández Millan I. Carcinoma of the penis. What to do with the regional lymph nodes? Arch Esp Urol 1994;47:349-62.  Back to cited text no. 15
Lont AP, Kroon BK, Gallee MP, van Tinteren H, Moonen LM, Horenblas S. Pelvic lymph node dissection for penile carcinoma: Extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol 2007;177:947-52.  Back to cited text no. 16
Slaton JW, Morgenstern N, Levy DA, Santos MW Jr., Tamboli P, Ro JY, et al. Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: Independent prognosticators for inguinal lymph node metastasis in penile squamous cancer. J Urol 2001;165:1138-42.  Back to cited text no. 17
Spiess PE, Hernandez MS, Pettaway CA. Contemporary inguinal lymph node dissection: Minimizing complications. World J Urol 2009;27:205-12.  Back to cited text no. 18
Solsona E, Iborra I, Rubio J, Casanova JL, Ricós JV, Calabuig C. Prospective validation of the association of local tumor stage and grade as a predictive factor for occult lymph node micrometastasis in patients with penile carcinoma and clinically negative inguinal lymph nodes. J Urol 2001;165:1506-9.  Back to cited text no. 19
Ficarra V, Zattoni F, Artibani W, Fandella A, Martignoni G, Novara G, et al. Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis. J Urol 2006;175:1700-4.  Back to cited text no. 20
Miralles-Guri C, Bruni L, Cubilla AL, Castellsagué X, Bosch FX, de Sanjosé S. Human papillomavirus prevalence and type distribution in penile carcinoma. J Clin Pathol 2009;62:870-8.  Back to cited text no. 21
Vokes EE, Agrawal N, Seiwert TY. HPV-associated head and neck cancer. J Natl Cancer Inst 2015;107:djv344.  Back to cited text no. 22
Bezerra AL, Lopes A, Landman G, Alencar GN, Torloni H, Villa LL. Clinicopathologic features and human papillomavirus dna prevalence of warty and squamous cell carcinoma of the penis. Am J Surg Pathol 2001;25:673-8.  Back to cited text no. 23
Ottenhof SR, Djajadiningrat RS, de Jong J, Thygesen HH, Horenblas S, Jordanova ES. Expression of programmed death ligand 1 in penile cancer is of prognostic value and associated with HPV status. J Urol 2017;197:690-7.  Back to cited text no. 24
Lohneis P, Boral S, Kaufmann AM, Lehmann A, Schewe C, Dietel M, et al. Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour-infiltrating T lymphocytes. Virchows Arch 2015;466:323-31.  Back to cited text no. 25
Wood HM, Angermeier KW. Anatomic considerations of the penis, lymphatic drainage, and biopsy of the sentinel node. Urol Clin North Am 2010;37:327-34.  Back to cited text no. 26
Rouviere H. Anatomy of the Human Lymphatic System. Ann Arbor (MI): Edwards Brothers Inc.; 1938. p. 215-7.  Back to cited text no. 27
Lopes A, Bezerra AL, Serrano SV, Hidalgo GS. Iliac nodal metastases from carcinoma of the penis treated surgically. BJU Int 2000;86:690-3.  Back to cited text no. 28
Kulkarni JN, Kamat MR. Prophylactic bilateral groin node dissection versus prophylactic radiotherapy and surveillance in patients with N0 and N1-2A carcinoma of the penis. Eur Urol 1994;26:123-8.  Back to cited text no. 29
Heyns CF, Fleshner N, Sangar V, Schlenker B, Yuvaraja TB, van Poppel H. Management of the lymph nodes in penile cancer. Urology 2010;76:S43-57.  Back to cited text no. 30
Hegarty PK, Dinney CP, Pettaway CA. Controversies in ilioinguinal lymphadenectomy. Urol Clin North Am 2010;37:421-34.  Back to cited text no. 31
Protzel C, Alcaraz A, Horenblas S, Pizzocaro G, Zlotta A, Hakenberg OW. Lymphadenectomy in the surgical management of penile cancer. Eur Urol 2009;55:1075-88.  Back to cited text no. 32
Catalona WJ. Modified inguinal lymphadenectomy for carcinoma of the penis with preservation of saphenous veins: Technique and preliminary results. J Urol 1988;140:306-10.  Back to cited text no. 33
National Comprehensive Cancer Network. Penile Carcinoma (Version 1.2018). National Comprehensive Cancer Network; 2019.  Back to cited text no. 34
Hakenberg O. EAU Guidelines on Penile Cancer: 2018 Update; 2018.  Back to cited text no. 35
Parra RO. Accurate staging of carcinoma of the penis in men with nonpalpable inguinal lymph nodes by modified inguinal lymphadenectomy. J Urol 1996;155:560-3.  Back to cited text no. 36
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;79:54-7.  Back to cited text no. 37
Coblentz TR, Theodorescu D. Morbidity of modified prophylactic inguinal lymphadenectomy for squamous cell carcinoma of the penis. J Urol 2002;168:1386-9.  Back to cited text no. 38
Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977;39:456-66.  Back to cited text no. 39
Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. JAMA Surg 1992;127:392-9.  Back to cited text no. 40
Horenblas S, Jansen L, Meinhardt W, Hoefnagel CA, de Jong D, Nieweg OE. Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol 2000;163:100-4.  Back to cited text no. 41
Lam W, Alnajjar HM, La-Touche S, Perry M, Sharma D, Corbishley C, et al. Dynamic sentinel lymph node biopsy in patients with invasive squamous cell carcinoma of the penis: A prospective study of the long-term outcome of 500 inguinal basins assessed at a single institution. Eur Urol 2013;63:657-63.  Back to cited text no. 42
Leijte JA, Hughes B, Graafland NM, Kroon BK, Olmos RA, Nieweg OE, et al. Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis. J Clin Oncol 2009;27:3325-9.  Back to cited text no. 43
Leijte JA, Kroon BK, Valdés Olmos RA, Nieweg OE, Horenblas S. Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma. Eur Urol 2007;52:170-7.  Back to cited text no. 44
Brouwer OR, van den Berg NS, Mathéron HM, van der Poel HG, van Rhijn BW, Bex A, et al. Ahybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. Eur Urol 2014;65:600-9.  Back to cited text no. 45
Markuszewski M, Polom W, Cytawa W, Czapiewski P, Lass P, Matuszewski M. Comparison of real-time fluorescent indocyanine green and (99m) Tc-nanocolloid radiotracer navigation in sentinel lymph node biopsy of penile cancer. Clin Genitourin Cancer 2015;13:574-80.  Back to cited text no. 46
Frontado LM, Brouwer OR, van den Berg NS, Mathéron HM, Vidal-Sicart S, van Leeuwen FW, et al. Added value of the hybrid tracer indocyanine green-99mTc-nanocolloid for sentinel node biopsy in a series of patients with different lymphatic drainage patterns. Rev Esp Med Nucl Imagen Mol 2013;32:227-33.  Back to cited text no. 47
Brouwer OR, Buckle T, Vermeeren L, Klop WM, Balm AJ, van der Poel HG, et al. Comparing the hybrid fluorescent-radioactive tracer indocyanine green-99mTc-nanocolloid with 99mTc-nanocolloid for sentinel node identification: A validation study using lymphoscintigraphy and SPECT/CT. J Nucl Med 2012;53:1034-40.  Back to cited text no. 48
Johnson TV, Hsiao W, Delman KA, Jani AB, Brawley OW, Master VA. Extensive inguinal lymphadenectomy improves overall 5-year survival in penile cancer patients: Results from the surveillance, epidemiology, and end results program. Cancer 2010;116:2960-6.  Back to cited text no. 49
Tobias-Machado M, Tavares A, Molina WR Jr., Forseto PH Jr., Juliano RV, Wroclawski ER, et al. Video endoscopic inguinal lymphadenectomy (VEIL): Minimally invasive resection of inguinal lymph nodes. Int Braz J Urol 2006;32:316-21.  Back to cited text no. 50
Tobias-Machado M, Tavares A, Silva MN, Molina WR Jr., Forseto PH, Juliano RV. Can video endoscopic inguinal lymphadenectomy achieve a lower morbidity than open lymph node dissection in penile cancer patients? J Endourol 2008;22:1687-91.  Back to cited text no. 51
Sotelo R, Sanchez-Salas R, Clavijo R. Endoscopic inguinal lymph node dissection for penile carcinoma: The developing of a novel technique. World J Urol 2009;27:213-9.  Back to cited text no. 52
Matin SF, Cormier JN, Ward JF, Pisters LL, Wood CG, Dinney CP, et al. Phase 1 prospective evaluation of the oncological adequacy of robotic assisted video-endoscopic inguinal lymphadenectomy in patients with penile carcinoma. BJU Int 2013;111:1068-74.  Back to cited text no. 53
Waigankar S, Yuvaraja T, Pednekar A, Wagaskar V. Surgical and oncological outcomes after robotic-video endoscopic inguinal lymphadenectomy in cN0/cN1 groins: Single institute series. Eur Urol Suppl 2017;16:e2439.  Back to cited text no. 54
Singh A, Jaipuria J, Goel A, Shah S, Bhardwaj R, Baidya S, Jain Comparing Outcomes of Robotic and Open Inguinal Lymph Node Dissection in Patients with Carcinoma of the Penis. J Urol 2018;199:1518-25.  Back to cited text no. 55
Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB. Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers. Eur Urol 2018;73:560-9.  Back to cited text no. 56
Velazquez EF, Ayala G, Liu H, Chaux A, Zanotti M, Torres J, et al. Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm. Am J Surg Pathol 2008;32:974-9.  Back to cited text no. 57
Leijte JA, Gallee M, Antonini N, Horenblas S. Evaluation of current TNM classification of penile carcinoma. J Urol 2008;180:933-8.  Back to cited text no. 58
International Penile Advanced Cancer Trial – An International Rare Cancers Initiative Study. (N.D.). Available from: [Last accessed on 2019 Jun 20].  Back to cited text no. 59


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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