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SYMPOSIUM |
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| Year : 2006 | Volume
: 22
| Issue : 4 | Page : 364-367 |
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Cancer penis: An overview
Ganesh Gopalakrishnan
Department of Urology, Christian Medical College, Vellore - 632004, India
Correspondence Address:
Ganesh Gopalakrishnan
Department of Urology, Christian Medical College, Vellore - 632004
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0970-1591.29127
Keywords: Cancer penis, ilioinguinal lymphadenectomy
How to cite this article:
Gopalakrishnan G. Cancer penis: An overview. Indian J Urol 2006;22:364-7 |
This issue of the journal has focused on penile cancer. It is quite evident from some articles and the current published literature that one could still have differences of opinion on the management of these cases. Whatever the issues on management, we need to constantly remind ourselves that penile cancer is preventable and if it does occur, then it is curable with timely surgical treatment. Many patients in our country do not give us that window of opportunity due to poor follow-up.
What brought them to the hospital in the first place is the penile lesion and when this has been removed they do not see the need to report unless they develop a complication like meatal stenosis or a fungating groin mass. In fact due to the social stigma of having the penis amputated or excised completely they do not even want to discuss this with their family lest they are ostracized. Some even do not tell their wives. With this social background and where evidence is lacking for clinical decisions, urologists are quite often in a dilemma as to what is the management for patients after treating the primary lesion. The morbidity and timing of inguinal lymphadenectomy is surely a major factor affecting clinical decisions. This against the background knowledge that metastatic inguinal nodes, spells a very poor outcome for patients with penile cancer.
While the editor has been gracious in devoting a symposium on this subject, I thought it appropriate to present two clinical situations and discuss their management against the backdrop of the contributing authors' articles.
Case 1
A 40-year-old male defaulted after undergoing a partial amputation for penile cancer. No comment was made about the status of the nodes at that time. He presented six months after surgery with bilateral inguinal adenopathy of significant size. The treating surgeon decided to remove these nodes. At surgery he found the nodes to be adherent to the femoral artery. A biopsy was taken and the wound closed. The contralateral side was not treated.
 Discussion | |  |
The above clinical picture is commonplace in our country. What could have been prevented with a timely inguinal lymphadenectomy has been lost; nevertheless, what one needs to focus on is the management strategy at this presentation.
It is quite obvious that these nodes are metastatic. What is needed at this stage is to establish whether inguinal lymphadenectomy is likely to be curative. It is therefore imperative that we establish further evidence of metastatic spread by appropriate imaging to see if external iliac or even paraaortic adenopathy is present. The presence of significant adenopathy at these sites will indicate that cure is highly unlikely and such patients do not survive beyond three to five years. If iliac adenopathy is significant and the inguinal nodes appear fixed, then combination chemotherapy as discussed (Raju Chacko) will shrink the masses and enable a re-look at surgical excision. Pizzocaro et al[1] analyzing 25 patients treated by radical ilioinguinal lymphadenectomy and chemotherapy for documented nodal metastasis reported that only four patients (16%) relapsed. The integration of systemic chemotherapy and pelvic lymphadenectomy might improve survival rates in patients with regionally advanced penile carcinoma.
In some situations, the status of the iliac nodes could be equivocal. In such a situation a fine needle aspiration cytology (FNAC) of the node or a minimally invasive approach (laparoscopic) to lymph node sampling could be done prior to excising the inguinal nodes. The few patients reported to date allows no conclusion on the best management of the iliac nodes.[2]
There are a few reports in the literature to indicate that there could be a minimal survival benefit if positive iliac nodes are excised provided no proximal adenopathy beyond exists. Ravi[3] and Srinivas[4] have recorded no survivors at five years in their respective series. The best management of iliac nodes is still debatable. Patients with metastatic iliac nodal involvement generally have poor survival and the value of pelvic lymphadenectomy remains controversial. However, the study by Lopes et al which was retrospective showed that pelvic lymphadenectomy may offer a cure in patients with single positive node. Leaving the patients alone is also not advisable as very soon the inguinal nodes will enlarge and fungate.
If iliac adenopathy is insignificant then an attempt to extirpate the inguinal lymph nodes on both sides must be done. The presence of metastasis to the iliac nodes with no inguinal involvement is anecdotal. If the femoral vessels are adherent then the tumor should be shaved off the vessels or if needed the vessel resected en block with the specimen and a graft substituted to restore limb circulation. The inguinal defect at this stage must be protected and one could use either a "sartorius slide" or better still a tensor fascia lata flap as described in this journal (Gupta). The iliac nodes should be excised at the same time on both sides. It is mandatory to have adequate cover if a graft has been used.
Could this clinical scenario have been prevented in the first instance? By having a close look at the histology of the penile amputation specimen-if the tumor was poorly differentiated then a bilateral inguinal lymphadenectomy should have been carried out at the initial presentation. If the tumor was well or moderately differentiated, then the depth of penetration should be looked at. Bilateral inguinal lymphadenectomy should be offered if the dept of invasion is > 8 mm (Bhagat). More recently additional factors have also been studied. Gustavo Cardoso[5] suggested that the pattern of invasion in addition to lymphovascular permeation are additional prognostic factors.
Case 2
A 68-year-old male undergoes partial penectomy. At that time the left groin nodes were palpable. He was prescribed antibiotics and was asked to return six weeks later. The patient presented six months later with fungating groin nodes on the left side.
| Discussion | | |
This is the scenario which is seen commonly in the Indian subcontinent. Once again that window of opportunity for cure might be lost. How does one address a situation of this nature at presentation and prevent this complication? It is well documented that in clinically palpable groin nodes, 50% could harbor malignancy; especially if the nodes are significant on one side. If this patient were to have undergone bilateral ilioinguinal dissection at presentation it could result in significant morbidity (30-81%). The nodes on histology could be negative for malignancy.
The advice given to the patient by the treating urologist was appropriate. Nevertheless, situations of this nature are not uncommon. Would an FNA cytology / biopsy of the groin node have helped? It might have. Moskovic[6] suggested that high-resolution ultrasound with guided cytology of the groin node might help in detecting metastasis.
One of the biggest drawbacks of FNAC and ultrasound is their poor predictability. A false-negative rate of 15% is quoted in clinically node-positive cases. In many patients a negative biopsy needs to be repeated and this leads to more anxiety and frustration. Ultrasound is again not diagnostic and the presence of infection in the node could alter architecture. More recently, dynamic lymphoscintigraphy (Hegarty) has been proposed as an investigation which holds promise of identifying metastatic nodes.
Dynamic scintigraphy helps in identifying a sentinel node. Dynamic sentinel node biopsy attempts to reduce the risk of complications in those with no metastasis without affecting the oncological outcome in those with metastasis. Only those with tumor-positive sentinel node undergo additional inguinal node dissection. Kroon[7] reported a 16% false-negative rate in the early days of evaluating this test, but after making adaptations, in the last 60 cases, no more false-negatives occurred. The articles do not seem to indicate the role of infection as a confounder in the analysis. We need to keep this factor in view in our country with many people walking barefoot. Just as is hypothesized that lymphatic channels could get blocked with metastatic tumor and prevent ingress of radioactive tracer, similarly, in chronic lymphadenitis, the lymphatics could suffer the same fate and create a false-negative situation. There is a large volume of data on cancer penis reported from Brazil. Losing patients to follow-up is common in that country too because a large number of their patients are from neighboring Paraguay (personal communication). D'ancona[8] in an attempt to circumvent the problem as has happened in this case, published a report on 26 cases of cancer penis where penectomy and bilateral modified inguinal lymphadenectomy was done simultaneously. Ten of these patients had palpable inguinal nodes; in four it was bilateral. Details of the operative procedures and boundaries of dissection are described in the article. They did a frozen section analysis of the nodes and if it was positive then a formal block dissection was completed. In a letter to the Editor, Journal of Urology[9] in response to the article I had raised some queries on this article, chiefly the duration to reporting the frozen section and the issue of false-negative reporting.
The complication rates were 36.8% for the modified inguinal lymphadenectomy and 87.5% for the complete lymphadenectomy. They argued that these rates are no different if performed subsequently as is the norm. In the final analysis, the nodes were negative bilaterally in 69% and two of them developed recurrence in less than two years after surgery and died.
More recently, it has been shown that a detailed analysis of the primary lesion in the penis is likely to indicate whether the inguinal nodes are the seat of metastases and thus offer early and if possible prophylactic lymphadenectomy. These factors include the grade of tumor, depth of the tumor, the presence of lymphovascular invasion and the pattern of invasion. Available literature indicates that a poorly differentiated tumor has greater metastatic potential and such patients should be offered prophylactic lymphadenectomy.
The grey zone is with tumors which are moderately differentiated. In this situation, the above mentioned factors need to be considered in multivariate analysis. They are all independent risk factors for nodal metastasis. Ficarra[10] in a recent publication generated a nomogram using a logistic regression model and claimed that in the presence of palpable lymph nodes vascular and/or lymphatic invasion embolization predicted metastatic lymph node involvement. However, further validation studies are required to confirm or refute these observations.
Coming back to the clinical scenario, we now have a patient with fungating groin nodes. In patients with fungating unilateral groin nodes, one often assumes that cure is unlikely. It is likely that proximal adenopathy if present could be secondary to an inflammatory resection. Chemotherapy at this time should be the first line of management. The article by Chacko in the issue of the journal outlines the protocol. In most patients there is a fairly dramatic response to combination chemotherapy. Following chemotherapy, the patient is re-evaluated for distal metastasis. Iliac nodes alone if present are not a contraindication to surgery. Nodes above the iliac bifurcation if significant would require treatment strategy to be revisited. Fungating nodes do pose an inherent dilemma. Leaving these alone increases the risk of femoral artery "blow-out". Palliative resection helps in improving quality of life. The risk of femoral artery erosion is handled by ligation of the external iliac artery in continuity close to the inguinal ligament.
It is thus clear from the data that we are still in a "no-win" situation as far as the disease is concerned. Waiting for clinical palpability and then offering lymphadenectomy is like "shutting the barn door after the horse has fled". Offering elective lymphadenectomy runs the risk of a negative surgical exercise and an unacceptable complication. At the recent SIU meeting in Cape town, South Africa, Nelson Netto[8] from Brazil was asked to give a state-of-the-art lecture on cancer penis. He has advocated immediate modified lymphadenectomy at the time of penectomy[8] and to perform frozen section. If nodes are positive then it is necessary to complete the groin dissection. It is evident that in the developing world and especially with cancer penis we probably need to be proactive and accept the morbidity rather than run the risk of fungating groin nodes. To my mind, in the last two decades, we seem to have achieved precious little. At this time what is lacking is clinical evidence on the management of clinically nonpalpable nodes. I would therefore suggest the following algorithm [Figure - 1] for the management of patients with cancer penis.
| Future directions for research | | |
As indicated by several authors, there are no randomized data to help manage such patients. Each department or consultant handles their patients based on the local situation. One feature stands out - that in all developing countries patients with penile cancer default after the penectomy. All pathologists need uniformity and look at a standard reporting format to opine on grade of tumor, depth of invasion (in mm), lymphovascular invasion and pattern of invasion.
What is needed at this time is to collate the data from various studies, outline a nomogram, plan multicentric randomized studies and derive best clinical evidence on the management of patients with penile cancer.
Through this issue, I am making a plea to all interested urologists who are willing to participate in a well-designed study to write to me. We can then channel all patients into a set pattern of management and with uniform pathological reporting of the specimen. This I believe will be a landmark national study and will hopefully pave the way for future research in Urology in India.
| References | | |
| 1. | Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin and methotraxate for inguinal metastasis from squamous cell carcinoma of the penis. Acta Oncol 1988;27:823-4.  |
| 2. | Lopes A, Bezerra AC, Searano SV, Hidalgo GS. Iliac nodal metastasis from carcinoma of the penis treated surgically. BJU Int 2000;86:690-3. |
| 3. | Ravi R. Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol 1993;72:817-9. [PUBMED] |
| 4. | Srinivas V, Morse MJ, Herr HW, Sojani PC, Whitmore WF Jr. Penile cancer: Relation of extent of nodal metastasis to survival. J Urol 1987;137:880-2. |
| 5. | Guimaraes GC, Lopes A, Campos RS, Zequi Sde C, Leal ML, Carvalho AL, et al . Front Pattern of invasion in squamous cell carcinoma of the penis: New prognostic factor for predicting risk of lymphnode metastasis. Urology 2006;68:148-53. |
| 6. | Moskovic EC, Shepherd JH, Barton DP, Trotk PA, Nasiri N, Thomas JM. The role of high resolution ultrasound with guided cytology of groin lymphnodes in the management of squamous cell carcinoma of the vulva: A pilot study. Br J Obstet Gynaecol 1999;106:863-7. |
| 7. | Kroon BK, Horenblas S, Estourge SH, Cont AP, Valdes Olmos RA, Nieweg OE. How to avoid false negative dynamic sentinel node procedures in penile carcinoma. J Urol 2004;171:2191-4. |
| 8. | d'Ancona CA, de Lucena RG, Querne FA, Martins MH, Denardi F, Netto NR Jr. Long term followup of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy. J Urol 2004;172:498-501. |
| 9. | Gopalakrishnan G. Re: Long-term follow-up of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy. J Urol 2005;173:1048. |
| 10. | Ficarra V, Zattoni F, Artibani W, Fandella A, Martignoni G, Novara G, et al . Nomogram prediction of pathological inguinal lymphnode involvement in patients with squamous cell carcinoma of the penis. J Urol 2006;175:1700-5. |
[Figure - 1]
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| Panse, N. and Sahasrabudhe, P. and Kashyapi, B. | | Indian Journal of Urology. 2012; 28(3): 325-328 | | [Pubmed] | |
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