LONG-TERM FOLLOWUP OF PENILE CARCINOMA TREATED WITHPENECTOMY AND BILATERAL MODIFIED

INGUINAL LYMPHADENECTOMY

CARLOS ARTURO LEVI D’ANCONA, ROBERTO GONC� ALVES DE LUCENA,FERNANDO AUGUSTO DE OLIVEIRA QUERNE, MARIO HENRIQUE TAVARES MARTINS,

FERNANDES DENARDI AND NELSON RODRIGUES NETTO, JR.From the Division of Urology, Faculdade de Ciencias Medicas da Universidade Estadual de Campinas, Sao Paulo, Brazil

ABSTRACT

Purpose: We evaluated modified inguinal lymphadenectomy in the treatment of penile carci-noma, analyzing the rate of complications compared to complete inguinal lymphadenectomy, thecomplications in performing lymphadenectomy and penectomy concomitantly, and the long-termlocoregional recurrence rate.Materials and Methods: A total of 26 patients with squamous cell carcinoma of the penis were

clinically assessed, and underwent penectomy and bilateral modified inguinal lymphadenectomyat the same operative time. Frozen section analysis of lymph nodes was performed and ifmetastases were detected a complete ipsilateral inguinal dissection was performed.Results: A total of 52 modified lymphadenectomies were performed. In 10 procedures lymph

node metastasis was present. Clinical staging presented false-positive and false-negative rates of50% and 7.9%, respectively. The complication rate for modified lymphadenectomy was 38.9% andfor complete inguinal lymphadenectomy it was 87.5%. Followup ranged from 5 to 112 months andmean followup of recurrence-free cases was 78 months (range 38 to 112). A total of 18 patientsunderwent bilateral negative modified inguinal lymphadenectomy and 2 of these experiencedlocoregional recurrence within 2 years after surgery.Conclusions: Modified inguinal lymphadenectomy causes a lower complication rate than com-

plete inguinal lymphadenectomy. Bilateral modified inguinal lymphadenectomy performed atthe same time as penectomy does not increase the complication rate. When frozen sectionanalysis is negative bilaterally, 5.5% of inguinal regions might still harbor occult metastasis.Modified inguinal lymphadenectomy is recommended as a staging procedure in all patients withT2–3 penile carcinoma. A straight followup is required for 2 years since all recurrence was withinthis period.

KEY WORDS: penile neoplasms, lymph node excision, neoplasm metastasis, lymphatic metastasis

Squamous cell carcinoma (SCC) accounts for more than95% of primary malignant penile neoplasia.1 SCC of thepenis is characterized by an essentially locoregional involve-ment affecting the inguinal, pelvic and periaortic lymphnodes. Hematogenic dissemination is rare even with the in-vasion of the corpora cavernosa and the rate of distant me-tastasis ranges from 1% to 10%.2 This makes penile carci-noma one of the few urological malignancies potentiallycurable with regional lymphadenectomy.3

In patients presenting with SCC of the penis 30% to 60%have palpable lymph nodes in the inguinal region.2, 3 In 50%of these patients this condition is caused by metastatic in-volvement and in the other half by inflammatory reactions.4Therefore, clinical staging is not a reliable parameter forguiding treatment. Patients with stage T2–3 penile SCCshould undergo inguinal lymphadenectomy regardless ofwhether lymph nodes are palpable.5 However, in 60% of casesno lymph node metastases are found in the resection speci-men.6 These patients underwent unnecessary node dissec-tion and were exposed to the well-known morbidity of theprocedure.Knowledge of pelvic and inguinal lymph node anatomy as

well as the preferred drainage path of penile tumors stimu-lated the development of various surgical techniques forgreater effectiveness with decreased morbidity.7, 8 Studies

conducted on inguinal lymphadenectomy involving the pres-ervation of the saphenous vein and restricting resection me-dial to the femoral vessels (modified lymphadenectomy) dem-onstrated a significant decrease in morbidity, but sincelocoregional recurrence rates varied is not clear whetherlocal control of the disease might be attempted.9–11

We assessed the incidence of complications secondary tomodified lymphadenectomy and, compared with complete in-guinal lymphadenectomy, verified whether the concomitantperformance of lymphadenectomy and penectomy increasedcomplications. We analyzed the long-term locoregional recur-rence rate to evaluate the results of modified inguinal lymph-adenectomy in the treatment of penile carcinoma.

PATIENTS AND METHODS

There were 26 patients who presented with squamous cellcarcinoma of the penis between 1994 and 1999 and wereincluded in this study. Patient age ranged from 44 to 94 years(mean 62, median 63). The patients were referred to theUrology Division after a disease onset that ranged from 2 to70 months (mean 14, median 8). The criteria for exclusionfrom study were poor clinical conditions for surgery, presenceof distant metastasis, ulcerated inguinal metastasis, previ-ous oncological treatment involving radiotherapy and/or che-motherapy, unresectable primary tumor, previous surgery ofAccepted for publication February 27, 2004.

0022-5347/04/1722-0498/0 Vol. 172, 498–501, August 2004THE JOURNAL OF UROLOGY® Printed in U.S.A.Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000132239.28989.e1

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inguinal nodes, patients with stage T1, carcinoma in situ andverrucous carcinoma.The clinical examination consisted of detailed palpation of

the penile shaft to verify the extent of the disease and pal-pation of the inguinal regions for lymph node assessment.The lymph nodes were considered clinically positive whenpalpable, fixed to the superficial or deep planes. Cases with-out any of these characteristics were considered N0. To as-sess the possibility of distant metastasis, chest x-ray andcomputerized tomography of the abdomen and pelvis weredone. Clinical staging was performed using the 1988 TNMsystem.12All patients underwent penectomy and modified inguinal

lymphadenectomy at the same operative time. Antibiotic pro-phylaxis with cefazolin was introduced during anestheticinduction and continued for 7 days. Low molecular weightheparin was administered as prophylaxis for deep venousthrombosis and maintained for 48 hours. An extremity com-pression hose was prescribed for all patients. Treatment forthe penile lesion followed the principle of complete tumorresection with a 2 cm minimum macroscopic safety marginand a histopathological assessment (frozen section) of theincision margins that confirmed absence of neoplasia in theremaining penile stump. Total penectomy associated withperineal ureterostomy was chosen when tumor resectionwould leave a penile stump smaller than 2 cm.All patients underwent bilateral modified inguinal lymph-

adenectomy.8 A 5 cm skin incision was made 2 cm below theinguinal arcade along the femoral vessels. The adipose andlymphatic tissues below Scarpa’s fascia were resected en blocwith the adductor longus muscle as the medial border, themedial surface of the femoral and saphenous veins as thelateral border, and the inguinal arcade as the superior bor-der, performing a triangle (see figure). Frozen section anal-ysis of lymph nodes was performed and if metastases wereabsent, the procedure was concluded and an aspirative drain

was maintained for at least 5 days. When metastases weredetected an ipsilateral complete inguinal lymphadenectomywas performed. In followup special attention was given to theinguinal region and the penile stump to verify if there wereany nodes or indurations. Followup was performed every 3months in the year 1, every 6 months in year 2 and then onceyearly.

RESULTS

There were 26 patients with squamous cell carcinoma ofthe penis who underwent penectomy and concomitant bilat-eral modified inguinal lymphadenectomy. The number of in-guinal regions was considered in this study and involved atotal of 52 lymphadenectomies. The preoperative clinical ex-amination revealed palpable lymph nodes in 10 patients(38.4%), 4 of whom had bilateral adenopathy, totalling 14(27%) inguinal regions.The modified inguinal lymphadenectomy was negative for

metastasis in 42 (81%) procedures. It was bilaterally positivein 2 (7.7%) patients and bilaterally negative in 18 (69%). Nosignificant difference was observed in the number of lymphnodes evaluated in patients with or without lymph nodemetastasis (6.5 and 5.4, respectively). Preoperative clinicalstaging presented false-positive and false-negative rates of50% and 7.9%, respectively, considering the anatomopatho-logical results of modified lymphadenectomy as a standard(table 1). The false-positive and false-negative rates obtainedin our study were 50% (7 of 14) and 13% (5 of 38), respec-tively, considering 3 patients at surgery and 2 others atfollowup.There were 8 patients whose frozen section biopsy was

positive and who underwent complete inguinal lymphadenec-tomy that was bilateral in 2. In all cases the anatomopatho-logical analysis of the nodal packet from the complete lymph-adenectomy revealed no metastasis. In 17 cases the peniletumors were well differentiated, in 8 they were moderatelydifferentiated and undifferentiated in 1. There was a higherrate of positive lymph nodes in the patients with well differ-entiated tumors but the difference was not statistically sig-nificant.Complications were classified as minor and major. Minor

complications included skin edge necrosis requiring no ther-apy, seroma formation not requiring aspiration and lymphdrainage. Major complications consisted of lymphedema in-terfering with ambulation. The minor complication rate forpatients who underwent modified lymphadenectomy and pe-nectomy was 36.8%, while in complete lymphadenectomy itwas 87.5% (p �0.05). Major complications occurred in 37.5%of patients who underwent complete inguinal lymphadenec-tomy and were absent in those who underwent modifiedinguinal lymphadenectomy (table 2).Followup ranged from 5 to 112 months. Mean followup of

recurrence-free cases was 78 months (range 38 to 112). Onepatient was lost to followup after 38 months, he was free fromdisease and the last clinical evaluation was considered final.Four patients died of causes unrelated to the disease, andthey were all free from disease at the last clinical evaluationsat 38, 50, 58 and 70 months.Among the 8 patients who underwent complete inguinal

lymphadenectomy 3 (37.5%) experienced locoregional recur-rence at 5, 8 and 11 months, and died of disease progression.

Limits of modified inguinal lymphadenectomy. a, lateral margin–saphenous and femoral vein. b, superior margin–inguinal ligament.c, median margin–adductor longus muscle.

TABLE 1. Comparison between clinical and surgical staging

Surgical No. Pos(%)

No. Neg(%)

No. Total(%)

Clinical:Pos 7 7 (50) 14 (27)Neg 3 (7.9) 35 38 (73)

Totals 10 (19.2) 42 (80.8) 52 (100)

LONG-TERM FOLLOWUP OF MODIFIED INGUINAL LYMPHADENECTOMY FOR PENILE CARCINOMA 499

One case of recurrence in the retroperitoneal lymph nodeswas detected by computerized tomography and confirmed byneedle biopsy, 1 was in the inguinal area and another in theperineum. The procedure was curative in the other patientswho were free of disease at a mean followup of 79 months(range 66 to 112). Of the 18 patients who underwent negativebilateral modified lymphadenectomy, locoregional recurrencedeveloped in 2 at 15 and 16 months of followup, 1 in the upperpart of the modified lymphadenectomy area and the other outof this area. Both patients underwent resection of the metas-tases but died of disease progression.

DISCUSSION

Due to the significant prognostic importance of inguinallymph node involvement in squamous cell carcinoma of thepenis, correct staging and, consequently, appropriate treat-ment of the inguinal lymph nodes are primordial factors inthe treatment of this disease.13 Clinical staging obtainedwith physical examination and imaging modalities cannotreliably confirm the presence or absence of lymph node me-tastasis.2, 7 Clinical staging presents a false-positive rate of50%2,14 that would result in a high number of unnecessarysurgeries, and a false-negative rate between 10% and 15%2,15

that would leave an unacceptable number of patients withoutadequate treatment. The false-positive and false-negativerates obtained in our study were 50% (7 of 14) and 13% (5 of38), respectively, considering 3 patients after surgery andanother 2 at followup. Our results were similar to thosefound in the literature. These data reveal the need for a moreeffective method to indicate lymph node involvement in pa-tients with SCC of the penis.Ultrasonographically guided fine needle aspiration biopsy

of lymph nodes has been suggested as the first investigationin clinically node positive and node negative cases. Obviouslythe result is only reliable when positive and the false-negative rates attain 15% in clinically node positive cas-es.14, 16 In many patients the biopsy needs to be repeated,causing anxiety and delay in treatment. Research on dy-namic sentinel node biopsy using lymphoscintigraphy hasindicated a potential benefit in selecting patients for lymph-adenectomy. Promising results have been obtained but fur-ther studies are necessary to establish the applicability ofthis method.17 In this study early modified lymphadenectomywas performed in all patients, allowing pathological stagingand concomitant treatment when necessary. Despite the fail-ure of 5.5% of procedures in 11% of patients this stagingmethod is comparable to other diagnostic methods.Studies conducted in patients with carcinoma of the penis

and no palpable lymph nodes showed that those who under-went early inguinal lymph node dissection presented a sig-nificantly higher survival rate than those treated with sur-veillance and salvage lymphadenectomy when nodes becamepalpable.18 Early inguinal lymphadenectomy is criticized forthe high complication rates and that many patients undergounnecessary surgeries. Modified inguinal lymphadenectomywas performed in this study and only minor complicationswere observed (36.8%), acceptable even for patients withoutlymph node involvement. Surgical complications of complete

inguinal lymphadenectomy occur in more than half the casesand vary between 50% and 84%.19 Modified lymphadenec-tomy is associated with lower morbidity and the rate of minorcomplications is 33% to 44%.10, 11 The minor complicationrates in this study were similar to those found in the litera-ture. Modified inguinal lymphadenectomy presented a com-plication rate of 36.8%, which was significantly lower(p �0.05) than the rate of 87.5% presented with completeinguinal lymphadenectomy. Many authors recommend thatpenectomy and lymphadenectomy be performed in a 2-stageapproach, guaranteeing a lower rate of complications.3, 19However, in this study the 2 procedures were done at thesame operative time and the complication rates were similarto those found in the literature for lymphadenectomy only.There are few data in the literature regarding the inci-

dence of locoregional recurrence after modified lymphadenec-tomy. One possible explanation is that this is a contemporarytechnique and its role in the management of SCC of the penisis not yet defined.20 A study with 13 patients demonstrated alocal recurrence rate of 15% after modified lymphadenecto-my.9 In 2 other studies with 9 and 12 patients there was nolocoregional recurrence after bilaterally negative modifiedlymphadenectomy in a long-term followup.10, 11 Of the 26patients enrolled in our study 18 (69.2%) underwent a bilat-erally negative modified lymphadenectomy and could bespared the morbidity of the complete inguinal lymphadenec-tomy. Although in these patients surgery could be consideredunnecessary, it has to be taken into account since the curerate is 62.5% with microscopic lymph node metastasis. It isnecessary to consider the unfavorable evolution of patientswho underwent surveillance and salvage lymphadenectomywhen nodes became palpable.2, 18 Of these patients in a meanfollowup longer than 6 years, 2 (5.5% of procedures or 2 of 36)had locoregional recurrence. This recurrence was in the first2 years, suggesting the necessity of closer followup. In 8(30.8%) patients the frozen section analysis was positive andthe procedure was extended to a complete inguinal lymphad-enectomy. Of these patients 5 (62.5%) were cured and asimilar cure rate is observed in the literature.19Analyzing all patients, the modified lymphadenectomy

performed at the same time as penectomy led to correcttreatment of the disease in 8 (30.8%), avoided morbidity for16 (61.5%) and failed in 2 (7.7%) patients. The failure can beexplained by the fact that the lymph node involved mighthave been outside the limits of dissection of the modifiedlymphadenectomy. We can consider the modified lymphade-nectomy a surgical staging procedure that promoted ade-quate staging and treatment in 92.3% of the patients in thiscohort study. In this study the tumor differentiation degreeindicated by many authors as a prognostic factor did notpresent any linear relationship with lymph node involve-ment.7, 13

CONCLUSIONS

Clinical staging of inguinal lymph nodes in patients withsquamous cell carcinoma of the penis should not be consid-ered in the treatment decision. The complication rate inpatients who underwent modified lymphadenectomy was sig-nificantly lower than in patients who underwent a completeinguinal lymphadenectomy. Modified lymphadenectomy canbe performed concomitantly with penectomy since the com-plication rate is the same when lymphadenectomy is per-formed alone. The modified lymphadenectomy can be recom-mended as a staging procedure to promote adequatetreatment. Followup is highly recommended every 3 monthsfor the first 2 years since all recurrence was within thisperiod.

Ms. Jane Kater Santos provided assistance in this work.

TABLE 2. Complications of modified and complete inguinallymphadenectomy

Minor ComplicationRate (%)

Major ComplicationRate (%)

Modified inguinal lymphadenectomy:Seroma 26.3Lymph drainage 10.5

Complete inguinal lymphadenectomy:Seroma 37.5 Lymphedema 37.5Lymph drainage 12.5Skin flap necrosis 37.5

LONG-TERM FOLLOWUP OF MODIFIED INGUINAL LYMPHADENECTOMY FOR PENILE CARCINOMA500

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EDITORIAL COMMENT

The authors report on a large group of patients with penile cancerall treated with partial penectomy and simultaneous modified ingui-nal dissection. They accurately identified all of the patients withsuperficial metastasis and proceeded with a more complete dissec-tion during the same setting. However, 2 men experienced locore-gional recurrence. I have experienced the same results with a fewpatients having local recurrence earlier than 2 years. This has led meto modify the extent of the modified dissection slightly. I now includethe nodal tissue below the fossa ovalis all the way to the femoralcanal, and dissect the femoral vein entirely and the medial aspect ofthe femoral artery below the inguinal ligament. This adds no addi-tional morbidity to the procedure and incorporates some nodal tissuethat may be missed with the original modified dissection, thus de-creasing the possibility of locoregional recurrence.

Raul O. ParraDivision of UrologyOregon Health and Science UniversityPortland, Oregon

REPLY BY AUTHORS

There are few data in the literature regarding the incidence ofloco-regional recurrence after modified lymphadenectomy. This sce-nario leads some investigators to change techniques based on theirown experience. Further studies addressing the results of these newapproaches are necessary. The role of modified lymphadenectomyshould be defined and a consensus on the treatment of penile carci-noma could be achieved. Based on our results complete inguinallymphadenectomy should be performed only for lymph nodes metas-tases.

LONG-TERM FOLLOWUP OF MODIFIED INGUINAL LYMPHADENECTOMY FOR PENILE CARCINOMA 501