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SYMPOSIUM
Year : 2006  |  Volume : 22  |  Issue : 4  |  Page : 351-354
 

Predicting inguinal metastases in cancer penis


1 Department of Urology, Christian Medical College, Vellore, India
2 Department of Pathology, Christian Medical College, Vellore, India

Correspondence Address:
Ganesh Gopalakrishnan
Department of Urology, Christian Medical College, Vellore
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-1591.29124

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   Abstract 

Objective: Is it possible to predict inguinal metastasis in penile cancer? Materials and Methods: This is a retrospective analysis of 90 cases of squamous cell carcinoma of penis. The analysis involved a study of archival specimens by a single consultant pathologist. The grade and depth of invasion of the primary tumor was studied. We tried to establish a correlation with clinical positivity as determined by physical examination, grade of primary tumor, depth of invasion and inguinal lymph node metastasis. Results: Metastatic status was known in 44 of 64 patients with clinically palpable inguinal nodes and 18 of 26 with clinically negative nodes. Of 62, 27 had lymph node metastasis in which 16 were poorly differentiated primary tumor. Inguinal lymph node metastasis was seen in six of nine (66.66%) when depth of invasion was more than 8 mm. Conclusions: In well-differentiated tumors with less than 3mm depth of invasion, active surveillance of the node could be recommended. In the rest, it may be wise in our country to offer prophylactic modified inguinal lymphadenectomy to avoid progression of disease from loss to follow-up. Morbidity can be reduced with a modified inguinal lymph node dissection in a majority and also by using principles of plastic surgery in the remainder.


Keywords: Cancer penis, inguinal node metastasis, lymphadenectomy


How to cite this article:
Bhagat SK, Walter N, Gopalakrishnan G. Predicting inguinal metastases in cancer penis. Indian J Urol 2006;22:351-4

How to cite this URL:
Bhagat SK, Walter N, Gopalakrishnan G. Predicting inguinal metastases in cancer penis. Indian J Urol [serial online] 2006 [cited 2019 Oct 14];22:351-4. Available from: http://www.indianjurol.com/text.asp?2006/22/4/351/29124


The prevalence of cancer of the penis is high in the developing world.

Poor penile hygiene and not being circumcised are the most common inciting factors. Surgery provides the best opportunity for cure. Unfortunately it is delayed in many cases as tight phimosis hides the lesion almost always in every case and thus the symptoms are ignored for a long time.

The penile lesion produces discharge, which is mistaken by patients for seminal fluid. Patient's compliance regarding follow-up also cannot be guaranteed. Most articles on penile cancer published from India and other developing countries report consistently of patients being lost to follow-up.[1] Delay enhances the opportunity for metastatic spread to the inguinal nodes.

The presence of associated infection in the primary lesion enhances the likelihood of inguinal adenopathy. In the South Indian subcontinent where the disease appears more common,[1] the habit of walking barefoot further increases the opportunity for palpable inguinal nodes.[2] Thirty to 60% of patients with penile cancer have palpable groin lymph nodes on presentation.[3] Fifty per cent of these patients have enlargement of nodes due to metastasis and other half due to inflammatory reaction.[4] In this scenario therefore, the mere presence of clinical adenopathy is not a reliable parameter for guiding treatment.

This article looks at certain parameters, which could help in establishing criteria to predict the likelihood of metastasis in inguinal nodes and by taking into account the above factors proposing a case for prophylactic groin dissection.

With numerous questions being unanswered, why not offer prophylactic lymphadenectomy to all patients. A balance needs to be struck between losing patients from lack of follow-up and presenting later with inoperable inguinal nodes and the morbidity of a groin dissection.[5] Catalona advocated that in patients with clinically negative nodes, a modified inguinal dissection be performed. If the frozen or paraffin section of inguinal nodes confirmed malignancy, then a complete adenectomy including removal of iliac nodes on both sides was advised.[6]


   Materials and Methods Top


This was a retrospective analysis of 90 cases of squamous cell carcinoma of the penis. The study period was from 1988 to 1995. All slides were archived and studied by a single consultant pathologist. Tumors were graded as well differentiated (Grade 1 or low grade when more than 75% of the tumor was composed of mature squamous cells), moderately differentiated (Grade 2 or intermediate grade with mature squamous cells in 25-75% of the tumor) and poorly differentiated (Grade 3 or high grade with less than 25% of the tumor composed of mature squamous cells and rest of the cells were immature). Mature squamous cell was defined as a relatively large tumor cell with abundant eosinophilic cytoplasm, often accompanied by keratinization and/or intercellular bridges. Immature squamous cell was defined as a smaller tumor cell with scanty relatively basophilic cytoplasm, usually lacking in keratinization or intercellular bridges. Cases were accepted for the study only if there was adequate amount of tumor in the sections - usually at least two slides. The depth of invasion was recorded microscopically to the nearest millimeter. It was measured from the deepest point of the invasive tumor up to the basement membrane of the covering stratified squamous epithelium. If the surface was ulcerated (i.e., no covering epithelium) then the measurement was made up to the ulcer floor. In all cases the measurement was made at right angles to the surface and never obliquely. Invasion of corpora cavernosa, corpus spongiosum and urethra was documented as absent or present. We had three groups of patients; group A where the depth of invasion was less than 3mm, group B between 4-8 mm and group C where depth of invasion was more than 8 mm.

Since this was a retrospective study, many slides were either not available for analysis due to breakage, loss of staining and importantly a lack of uniform policy in reporting the original histology as per the present criteria. Therefore, while the written report was still available we had to discard 38 specimens. The decision to carry out inguinal lymphadenectomy was left to the consultant-in-charge of the case and was not according to a fixed protocol. We attempted to arrive at a correlation between clinical lymph node positivity and metastasis, grade of tumor and metastasis and depth of invasion and presence of lymph node metastasis, thus trying to establish a clinico-pathological correlation. Thus out of an initial total of 90 cases we were finally able to analyze 62 patients and the rest were excluded due to lack of proper retrieval of the archival specimen.


   Results Top


Of 90 patients, 64 had clinically palpable groin nodes and 26 had nonpalpable nodes. Of the 64 patients with palpable nodes, metastatic status was known in 44 patients. In 23 with lymph node metastasis, the primary tumor was poorly differentiated in 14 [Table - 1]. In 26 patients with clinically negative inguinal nodes, metastatic status was known in 18 patients, 14 (78%) had no evidence of metastasis [Table - 2].

Depth of invasion was available in 52 patients. When depth of invasion was between 0-3 mm, (n = 19) only one had evidence of nodal metastasis in whom primary tumor was poorly differentiated. In patients with depth of invasion was more than 8 mm, (n = 9) metastasis was seen in six (66.66%), which was statistically significant ( P = 0.001). When the depth of invasion was between 4-8 mm an equal number of patients (12) had presence or absence of inguinal metastasis [Table - 3].


   Discussion Top


The main objective in the management of cancer is cure,, freedom from recurrence and better quality of life with survival benefit. The prognosis in penile cancer is based on accurate staging, which involves the locoregional lymph node status. The battle against penile cancer is won or lost at the level of the inguinal nodes. While the main prognostic indicator of survival is nodal metastases, the management of regional lymph nodes still remains controversial. Our data suggests that clinical palpability of inguinal node appears to be the norm and this appears to be related to delayed diagnosis, superadded secondary infection and walking bare foot. Thirty to 60% of patients with penile cancer have palpable groin lymph nodes on presentation.[3] Fifty per cent of these patients have enlargement of nodes due to metastasis and the other half due to inflammatory reaction.[4] In this scenario therefore, the mere presence of clinical adenopathy is not a reliable parameter for guiding treatment.

Irrevocable proof of malignancy in the inguinal nodes is histology. If there is a genuine sentinel node, then sampling that lymph node will solve the problem. Unfortunately, a truly sentinel node has not been identified. Cabanas[7] proposed that the node medial to the junction of the superficial epigastric and saphenous vein was the primary echelon of drainage in penile cancer. However, Cabana's work has not been substantiated by others. The very high false negative rates have left many to question its value.[8]

Numerous tests have been proposed to try and find an answer to this clinical problem. More recently, dynamic lymphoscintigraphy has also been advocated as a test of some potential in selecting patients for lymphadenectomy. Promising results have been obtained but further studies are necessary to establish the applicability of this method.[9]

It would however appear from data accrued that the factors which determine the metastatic potential are the grade of tumor and depth of penetration.[10] It has been shown in patients with high-grade lesions, that a significant proportion (78%) have metastasis in the inguinal node and early prophylactic lymphadenectomy will improve cancer control.[10] Waiting till the node becomes clinically positive and then undertaking lymphadenectomy significantly reduces the survival advantage.[11]

Of this the most controversial issue is the management of patients with a clinically negative groin examination at the time of diagnosis. Over the past decade, sentiment has moved towards earlier lymphadenectomy in selected patients with penile cancer. Studies have shown survival benefit in patients with microscopic metastasis who had undergone prophylactic inguinal lymphadenectomy compared to those with initially negative nodes on physical examination who subsequently had recurrent disease.[10] Several studies in patients with clinically negative inguinal lymph nodes have convincingly shown that the strongest predictors of inguinal metastasis are primary tumor stage, grade and the presence of lymphatic or vascular invasion.[12] Few studies have shown the importance of the depth of invasion in assessing lymph node metastasis.[10],[13] Groin lymph node dissection, apart from being potentially curative, also provides the pathologic lymph node status, the most important prognostic information in penile squamous cell carcinoma. The main drawback of inguinal block dissection is its morbidity, which could be permanent.[14] Clinical staging obtained with physical examination and imaging modalities cannot reliably confirm the presence or absence of lymph node metastasis.[15] Clinical staging presents a false-positive rate of 50%[15] that would result in a high number of unnecessary surgeries. A false-negative rate between 10-15%[15],[16] would leave an unacceptable number of patients without adequate treatment.

Clinical false positivity and false negativity obtained in our study were 47.72% (21 of 44 palpable nodes were pathologically negative) and 22.22% (four of 18 nonpalpable nodes were pathologically positive) respectively. Our results were similar to those found in the literature.[17] These data show the need for a more effective method to indicate nodal metastasis in a patient with squamous cell cancer of the penis. The utility of tumor grading alone for cancer penis is controversial as the majority of studies report a correlation[17] but some find no association.[14] Our study revealed positive correlation between grade and nodal metastasis. Measurement of depth of invasion of tumor is an important technique for determining prognosis in malignant melanoma and vulvar and cervical carcinoma. Some studies have also revealed a correlation between the depth of invasion and nodal metastasis in penile cancer.[5],[17]

In our study when the depth of invasion was less than 3 mm the nodal metastasis rate was 5% and it was 66.6% when the depth was more than 8 mm, which is statistically significant ( P =0.001). In this study we also found that tumor grade and was useful in predicting the presence of nodal metastasis in clinically positive nodes.

It has been reported that 50% of the palpable inguinal nodes harbor metastasis in cancer penis.[4] This has also been noted in our study (52.27%). When the depth of invasion was more than 8 mm, 66.67% of patients had inguinal node metastasis. The depth of invasion is arbitrary; while some people have considered 6 mm[13] as the upper limit, we have placed this figure as 8 mm. This was our pathologist's decision. Had we accepted 6 mm depth of invasion as the upper limit it is likely that more patients would have fallen into the metastatic group. What we would like to emphasize is that any invasion beyond 3 mm requires serious consideration of prophylactic groin dissection in view of unreliable patient follow-up. We do realize that the current literature looks at lymphovascular invasion as an additional parameter for metastatic potential. Unfortunately, this parameter was not studied in this series.[18]

In our country, patients being lost to follow-up and subsequent readmission with obvious metastatic nodes, coupled with clinical palpability of inguinal nodes due to walking barefoot suggests that we need to look at a different strategy in the management of these patients if we have to achieve a cure. In view of the clinical scenario in our country and combining the histological features, grade and depth of invasion of the primary tumor we suggest that all patients who have high-grade lesion and / or depth of invasion more than 8 mm should have inguinal lymphadenectomy at the outset. Those with depth of invasion less than 3 mm can be safely followed up provided the lesion is of low grade. Additionally, when the depth of invasion is 4-8 mm we recommend a modified inguinal lymphadenectomy at the outset. If either frozen or paraffin section indicate metastasis then a completion bilateral iliac lymphadenectomy needs to be carried out. The logistics of performing frozen section is debatable and difficult as the inguinal nodes number approximately 10 to 15. How does one decide which node to send for frozen section? Should the entire nodal package be studied? How long does it take for the pathologists to report on the specimen and with confidence?[19],[20] The quality of frozen section is not as good as of paraffin section. The presence of associated inflammation poses an additional problem in reporting a frozen specimen in an ill-defined tumor. The real worry is false negativity on the frozen section. The morbidity of the inguinal lymphadenectomy can be reduced not only by adhering to the surgical procedure described but also by not hesitating to use the principles of plastic surgery to achieve a cosmetic result.


   Conclusions Top


In view of the high prevalence of penile cancer and its potential to be cured we need to adopt a quasi aggressive approach in these patients. This needs to be balanced against the morbidity of inguinal lymphadenectomy and the fact that our patients present late and do not return for follow-up. We feel that patients with clinically palpable inguinal nodes and primary tumor with depth of invasion > 8 mm should be offered inguinal lymph node dissection. A modified inguinal lymphadenectomy should be offered in patients with depth of invasion more than 3 mm in primary tumors as 50% of the patients are likely to have lymph node metastasis. Active surveillance of the inguinal nodes could be recommended in well-differentiated tumors with less than 3mm depth of invasion. Morbidity can be reduced with a modified inguinal lymph node dissection in a majority and also by using principles of plastic surgery in the remainder.

 
   References Top

1.Rangabashyam N, Gnanaprakasam D, Meyyappan, Vijayalakshmi SR, Thiruvadanam BS. Carcinoma of penis. Review of 214 cases. J R Coll Surg Edinb 1981;26:104-9.  Back to cited text no. 1    
2.Wapnick S, MacKintosh M, Mauchaza B. Shoelessness, enlarged femoral lymph nodes and femoral hernia. A possible association. Am J Surg 1973;126:108-10.  Back to cited text no. 2    
3.Ornellas, AA, Seixas AL, Marota A, Wisnescky A, Campos F, de Morales JR. Surgical treatment of invasive squamous cell carcinoma of the penis: Retrospective analysis of 350 cases. J Urol 1994;151:1244-9.  Back to cited text no. 3    
4.Abi-Aad, AS deKernion JB. Controversies in ilioinguinal lymphadenectomy for cancer of the penis. Urol Clin North Am 1992;19:319-24.  Back to cited text no. 4    
5.Ravi R. Morbidity following groin dissection for penile carcinoma. Br J Urol 1993;72:941-5.  Back to cited text no. 5  [PUBMED]  
6.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. 6    
7.Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977;39:456-66.  Back to cited text no. 7  [PUBMED]  
8.Perinette E, Crane DB, Catalona WJ. Unreliability of sentinel lymphnode biopsy for staging penile cancer. J Urol 1980;124:734-5.  Back to cited text no. 8    
9.Tanis PJ, Lont AP, Meinhardt W, Olmos RA, Nieweg OE, Horenblas S. Dynamic sentinel node biopsy for penile cancer: Reliability of a staging technique. J Urol 2002;168:76-80.   Back to cited text no. 9  [PUBMED]  
10.McDougal WS. Carcinoma of the penis: Improved survival by early regional lymphadenectomy based on the histological grade and depth of invasion of the primary lesion. J Urol 1995;154:1364-6.  Back to cited text no. 10  [PUBMED]  
11.Theodorescu D, Russo P, Zhang ZF, Morash C, Fair WR. Outcomes of initial surveillance of invasive squamous cell carcinoma of the penis and negative nodes. J Urol 1996;155 : 1626-31.  Back to cited text no. 11  [PUBMED]  
12.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. 12    
13.Emerson RE, Ulbright TM, Eble JN, Geary WA, Eckert GJ, Cheng L Predicting cancer progression in patients with penile squamous cell carcinoma: The importance of depth of invasion and vascular invasion . Mod Pathol 2001;14:963-8.  Back to cited text no. 13    
14.Horenblas S, van Tinteren H, Delemarre JF, Moonen LM, Lustig V, Van Waardenburg EW. Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes. J Urol 1993;149:492-7.  Back to cited text no. 14    
15.Horenblas S. Lymphadenectomy for squamous cell carcinoma of the penis, Part 1: Diagnosis of lymphnode metastasis. BJU Int 2001;88:467-72.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Horenblas S, van Tinteren H, Delmarre JF, Moonen LF. Lustig V, van Waardenburg EW. Squamous cell carcinoma of the penis III. Treatment of the regional nodes. J Urol 1993;149:492-7.  Back to cited text no. 16    
17.Solsona E, Iborra I, Rubio J, Casanova JL, Ricos JV, Calabuig C. Prospective validation of the association of local tumor stage and grade as a predictive factor for occult lymph node micro metastasis in patients with penile carcinoma and clinically negative inguinal lymph nodes. J Urol 2001;165:1506-9.   Back to cited text no. 17  [PUBMED]  
18.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;175:1700-5.  Back to cited text no. 18    
19.d'Ancona CA, de Lucena RG, Querne FA, Martins MH, Denardi F, Netto NR Jr. Long-term follow up of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy. J Urol 2004;172:498-501.  Back to cited text no. 19    
20.Gopalakrishnan G. Re: long-term follow-up of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy. J Urol 2005;173:1048.  Back to cited text no. 20    



 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]



 

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