Uro-oncology Consensus Meeting 1-2 April, 2000 Singapore.

From 1968 to 1997, there were 212 cases of penile cancer registered with the Singapore Cancer Registry representing about 0.3 percent of all cancers in Singapore. Although fewer in number as compared with other malignancies, its diagnosis and treatment impacts significantly on the psychology and sexuality of the patient.

This present guideline is an outcome of comprehensive literature review of major reports an extensive discussion amongst the penis cancer workgroup. The recommendations were presented at the Second Uro-oncology Consensus Meeting held on 1-2 April 2000, Singapore. This guideline was derived from the consensus drawn from the above meeting.

This guideline will serve as an updated reference of the practical management of patients suffering from penile cancer for family physicians, as well as specialists interested in the practice of uro-oncology.

A. Etiology and risk factors

Certain geographical regions show increased relative incidence of penile cancer, such as in parts of India, China and Africa. However, the incidence is seen to be falling in other populations, and this is attributed to rising socioeconomic status. Tobacco use is an independent risk factor, with a dose-response relationship.

Neonatal circumcision is a well established negative risk factor. This protection is, however, not complete. The timing of circumcision is important; circumcision after infancy confers less protection than neonatal circumcision. There are however other considerations for neonatal circumcision apart from its beneficial risk reduction for penile cancer, including social and religious factors.

Other risk factors discussed were phimosis, balanitis, previous trauma and sexual habits; there is conflicting evidence on the impact of these factors, which reflect our lack of understanding of the aetiology of the disease. In addition, the relationship of human papillomavirus subtypes remains to be clearly elucidated.

B. Diagnosis of penile cancer and Histology of premalignant conditions

The most common presentation for penile cancer is the lesion itself. It may vary from an area of induration or erythema, an ulceration or nodule, to a large exophytic growth. Phimosis may obscure the lesion and result in delay in seeking medical attention. Confirmation of penile cancer requires histological sampling, to distinguish between carcinoma-in-situ and invasive carcinoma. An adequate biopsy allowing the determination of invasiveness is considered the minimum requirement for this.

As a review, the histological distinction between the different types of pre-malignant conditions were discussed, viz, Erythroplasia of Querat, BowenⳠdisease, Bowenoid papulosis, Condylomata acuminatum and Giant Condyloma of Buschke-Lowenstein. Verrucous carcinoma was also described, with emphasis on the local aggressiveness without metastases.

C. Staging of Penile Cancer

The consensus meeting agreed to adopt the 1987 UICC TNM classification for penile cancers, which supercedes the 1978 classification. (See Appendix A) The proposed modification by McDougal which includes the histological grade of the tumour was discussed, but not adopted because it has not gained wide acceptance.

There is disparity between clinical and pathological staging of primary tumour in about a quarter of cases. Both ultrasonography ( US ) and computed tomography ( CT ) has no role in assessment of the primary lesion. Magnetic resonance imaging ( MRI ), however, may be superior to the other radiological methods in assessment of primary tumour

With regards to the presence of lymph node disease clinical examination is unable to distinguish between reactive and metastatic nodes. Lymphangiography is not recommended at present with its pitfalls and limitations. CT and MRI may be used to monitor regional lymph nodes especially when primary tumour had been removed and the patient was started on antibiotics. The role of MRI with ultrasmall superparamagnetic iron oxide particles needs further evaluation.

Sentinel lymph node biopsy is an unreliable indicator of lymph node involvement. The role of fine needle and aspiration cytology ( FNAC ) is linked to management policy of regional lymphadenopathy. If the patient had the primary lesion excised and was to undergo surveillance for regional lymphadenopathy; FNAC could be employed to establish whether there is any lymph node disease.

With regards to distant metastases, for diseases less than a Stage T2 and Grade 2, a chest X-ray ( CXR ), liver function test ( LFT ) and serum calcium level is sufficient as screening for metastatic disease. For disease more advance than that, a CT pelvis and bone scan would be useful. Again the role of using superparamagnetic iron oxide in MRI for detection of liver metastases requires further evaluation.

D. Prediction of regional LN status

Regional lymph node status is an important prognostic indicator in carcinoma of the penis. Five year survival in patients without lymph node involvement ranges from 71 to 95 % , whereas the range is 28 ?% for those with lymph node involvement. By identifying factors predictive of lymph node involvement, we aim to avoid the morbidity of unnecessary lymphadenectomy in those unlikely to benefit, and improve the survival outcome in patients who are likely to benefit from lymphadenectomy.

75 ?0 % of poorly differentiated tumours would have regional lymph node involvement, compared with 12 ? % in well to moderately differentiated tumours. Tumours involving the corpora are more likely (61 ? %) to involve lymph nodes . Tumours not involving the corpora are associated with a 5 ? % incidence of lymph node involvement.

Others factors identified as having a positive association with regional lymph node involvement include lymphatic & venous embolisation , tumour thickness ( > 5mm) , and T stage (as according to UICC TNM 1978).

E. Surgery for the primary tumour

Penectomy, be it partial or total, has long been regarded as the standard surgical therapy for local control of carcinoma of the penis. Local recurrence in the published literature ranges from 0 to 5%. The recommended margin of resection is 15 to 25 mm.

Various issues has to be addressed when considering conservative therapy for penile cancer. These will include psychological issues of penile surgery, histology and location of the tumour, surgical fitness, and recurrence rates and possible salvage surgery.

Small lesions of prepuce have been treated with circumcision alone; however, recurrence rates as high as 50% have been reported. Local wedge resection preserve more penile length, but also has recurrence rates up to 50%. Cryosurgery, laser therapy and topical 5-fluorouracil may be effective for superficial cancers or carcinoma-in-situ. MohⳠ micrographic surgery remains a technique appropriate only specialised centres.

F. Treatment Of Inguinal Lymphadenopathy In Penile Carcinoma

Whether the inguinal lymph nodes are palpable or not, the primary tumour is treated accordingly first.

Lymphadenectomy in node-positive disease results in a 20-50% 5-year disease-free survival. However not all enlarged inguinal lymph nodes are metastatic nodes. Subjecting all patients with palpable inguinal lymph nodes to lymphadenectomy may result in over-treatment and unnecessary morbidity.

If the inguinal lymph nodes are enlarged at presentation, a course of antibiotics should be given with the intention that inflammatory changes will resolve. The inguinal nodes are reassessed four to six weeks later by clinical palpation which has been noted to be practical and acceptably accurate. By then the pathological stage and grade would have been known also and this information may help in deciding on further surgery.

Whether the palpable nodes are unilateral or bilateral, it is advocated that a bilateral lympadenectomy be done due to the fact that 50 % of the lymphatics have cross-over drainage. The radical lymphadenectomy entails the removal of both the superficial and deep inguinal lymphatic chains. However, the surgery carries a high morbidity and a mortality rate of 3%. Major complications include disabling lymphadema (20 ?%), seroma (15 ?%), skin flap necrosis (14 ?%) and wound infection (10 ?%).

The modified inguinal lymphadenectomy is designed to reduce complication rates, but is not recommended because published data on this method involves small numbers of patients, and the results have been conflicting.

There is currently no proven advantage in removing the pelvic nodes. The presence of metastatic pelvic lymph nodes usually denote a grave prognosis.

In patients with clinically negative inguinal examinations on presentation, there is the controversy of whether a lymphadenectomy should be performed on a prophylactic basis. There is the potential survival benefit of early treatment by removing micrometastasis while it is still curable versus the surgical complications of an extensive operation. Current available evidences revealed that prophylactic lymphadenectomy should be undertaken if the primary tumour is moderately or poorly differentiated or the primary tumour invades the corpus spongiosum or cavernosum. Otherwise surveillance of the inguinal region with close follow up is a reasonable option.

G. Radiotherapy

Local radical radiotherapy is an alternative treatment to surgery in selected T1 and T2 tumours (See Appendix A). Either brachytherapy or teletherapy can be used or a combination of both. There is obvious advantage of organ preservation and cosmesis and salvage surgery is possible.

Post operative radiotherapy after a partial or complete amputation may be offered in selected patients.

Local palliative radiotherapy is possible for inoperable tumours and in patients who are medically unfit for palliative surgery. Inoperable groin nodes can also be approached with palliative radiotherapy. However, itⳠimpact is limited and morbidity is severe.

Conclusions

The consensus meeting focused primarily on the surgical management of penile cancer as it forms the mainstay of treatment, both in the curative and in the palliative settings. There still remains many controversies, particularly with regard to the impact and management of inguinal node disease. As new and more accurate data with higher levels of evidence becomes available, these guidelines will need to be constantly processed, updated and refined to remain relevant.

4. Etiology and Risk Factors

Incidence and socioeconomic status

The incidence of penile cancer varies from 0.8 per 100000 to 10 per 100000. Low incidence areas include developed countries, high risk areas are in some parts of China, India and Africa.

There is no direct link of any specific underlying factors to carcinoma of the penis. The risk is higher in those with lower socioeconomic status, however, falling incidence is seen in some populations. (1)

Tobacco

Smoking is a demonstrated independent risk factor for Ca penis. There is a dose-response relationship Tobacco remains a risk regardless of method of use, such as cigarettes, chewing or snuff. (2) (3) (4)Therefore, the argument for smoking cessation as well as avoidance of other forms of tobacco is strengthened by the increased risk for penile cancer. (C/III)

Sexually transmitted diseases and Sexual Habits

There is no correlation with syphilis (5) or any evidence associated with sexual transmission (3). A history of genital warts, however, is associated with increased risk. (2) (B/ III)

There is no correlation between the age of first intercourse and risk of penile cancer (6). The number of lifetime sexual partners was not significant in two studies, whereas another study showed that more than 30 lifetime partners is associated with increased risk (6) (3). Sexual relations outside marriage may be important (6). These conflicting results with sexual habits reflect our lack of understanding of the aetiology of the disease.

Circumcision

Neonatal circumcision is a well established negative risk factor.(7) This protection is, however, not complete. The timing of circumcision is important - circumcision after infancy confers less protection than neonatal circumcision. (2) (8). There are however other considerations for neonatal circumcision apart from its beneficial risk reduction for penile cancer, including social and religious factors. It was the consensus that poor personnel hygiene without circumcision increases the risk of penile cancer. (GPP)

Phimosis, balanitis, trauma

In uncircumcised males, the presence of phimosis or the history of paraphimosis are risk factors. (6). The presence of smegma is also a risk factor (9). The risk from a positive history of balanitis is conflicting. Previous trauma/rash may also be a factor (3). In this review, no study on the effect of early treatment of phimosis was found. Therefore, while phimosis is a risk factor, it is unclear if treatment will significantly reduce the risk.

HPV infection and cervical cancer

There is a suggested relationship between cervical cancer in the female, and penile cancer. This is thought to be related to the effect of infection with human papilloma viruses. HPV types 6 and 11 are considered low risk, whereas Types 16, 18, 31, 33 are high risk for malignant change. There is no positive relationship with cervical carcinoma in patientⳠwife/partner. (10). The incidence of HPV in penile cancers is markedly less than that in cervical cancers; about 15 ?% compared to 70-80%. (11)

The presence of HVP is more often associated with less well differentiated cancers, and bowenoid change. (12) (13) The presence in some tumours and not others may reflect 2 different aetiologies. (14) The low risk HPV types 6 and 11 have been reported in some cases of penile cancer. (15)

The role of HPV in the aetiology of penile carcinoma remains to be fully elucidated. There may be separate pathological mechanisms either involving or not involving specific viral strains.

Diagnostic Confirmation of Penile Carcinoma

Confirmation of penile cancer requires histological sampling, to distinguish between CIS and invasive carcinoma.

An adequate biopsy allowing the determination of invasiveness is considered the minimum requirement for this. Cytology and superficial biopsy are considered inadequate for histology. (GPP)

Histology

The various histological types of carcinoma-in-situ and pre-malignant conditions are detailed below:

First described by Tarnovsky in 1891, the term "erythroplasia" applied by Queyrat in 1911. It is characterised by bright red, well-defined, minimally glistening, velvety, persistent plaques on the glans penis and prepuce. It usually occurs in the 5^th and 6^th decades of life. It is solitary in 50% of patients. 10% progress to invasive carcinoma, 2% develop distant metastases. (16)

First described by Bowen in 1912. It refers to carcinoma-in-situ of both sun-exposed and sun-protected skin. Histologically it is similar to erythroplasia of queyrat but without the red clinical appearance, or when it involves the penile shaft. Grossly it appears as crusted, sharply demarcated scaly plaques, and microscopically, it is almost identical to erythroplasia of queyrat with minor differences (due to differing anatomic locations). 5% to 10% progress to invasive carcinoma. There is also a possible association with visceral cancers (respiratory, gastrointestinal, urogenital) (17)

This term was used by Wade in 1978 to describe lesions on the penile shaft or perineum of young men. It occurs on the penile shaft, with multicentric papules ranging from 2 to 10mm. The papules may coalesce to form plaques resembling condyloma acuminatum. Microscopically there is variable hyperkeratosis, parakeratosis, irregular acanthosis, papillomatosis, with usually more maturation of keratinocytes than in erythroplasia of queyrat or BowenⳠdisease.

It has an indolent clinical course, and responds to conservative treatment (local excision, topical or laser treatment). Its behaviour is different from erythroplasia of queyrat and BowenⳠdisease; there is no progression to invasive cancer or association with visceral cancer. Spontaneous regression can occur. (18) (19) (20)

This is a tumour-like condition, associated with Human PapillomaVirus: HPV 6,11 (in lesions without dysplasia); 16,18,31,33 (in lesions with dysplasia). (21) (22)

It involves the corona of glans, penile meatus, fossa navicularis urethrae, scrotal skin, perineum. Grossly, it is flat, with delicate papillary or warty, cauliflowerlike appearance. Microscopically, there is squamous proliferation with acanthosis and papillomatosis, with orderly epithelial maturation, hyperkeratosis, parakeratosis, and koilocytotic atypia. There is minimal cytologic atypia. Mitoses are usually basal. Treatment with podophyllin or lasers may result in bizarre cytologic changes that raise the possibility of malignancy. (23)

This lesion needs to be distinguished from verrucous carcinoma. The consistent absence of HPV 6,11,16,18,31 in verrucous carcinoma suggests that they are different entities. (24). These HPV are the same as in condylomata acuminatum with a similar frequency. (25) (26)

This tumour makes up 5% to 16% of penile malignancies. It occurs at the coronal sulcus, and spreads to the glans and preputial skin. Grossly it is a large, fungating tumour, ulcerated, warty, and burrowing through normal tissue. Microscopically, it is a well-differentiated squamous cell carcinoma, with exophytic and endophytic papillary growth. There is a broad-based pushing pattern of infiltration. There is minimal cytologic atypia, with mitoses rare. There may be vacuolated koilocyte-like change, but without true koilocytes. It is locally aggressive but does not metastasize

6. Staging methods

Primary tumour ( T )

There is disparity between clinical and pathological staging of primary tumour in about a quarter of cases. (27) (28)

Both ultrasonography ( US ) (29) and computed tomography (CT) (30) had no role in the assessment of the primary lesion. Magnetic resonance imaging ( MRI ) appeared superior to the other radiological methods in the assessment of the primary tumour (31) but its role is dependent on the management policy of regional lymphadenopathy.

Lymph node status ( N )

Again, clinical examination is unreliable with regards to the presence of lymph node disease. (32) (33) (B/III)

Lymphangiography is not recommended at present with its pitfalls and limitations. (34) (35) (36) (B/III)

CT and MRI may be used to monitor regional lymph nodes especially when primary tumour had been removed and the patient was started on antibiotics. This is suggested as an optional investigation depending on the characteristic of the tumor, the personnel experience of the surgeon and the availability of the tests. (GPP)

The role of MRI with ultrasmall superparamagnetic iron oxide particles needs further evaluation and at present is not recommended. (C/IV). (37) (38) (39) (40)

Sentinel lymph node biopsy is an unreliable indicator of lymph node involvement. (41) (42) The role of dynamic sentinel node biopsy (43) using technetium 99 and gamma detection probe is still experimental. (B/III)

The role of fine needle and aspiration cytology ( FNAC ) (44) (45) is linked to management policy of regional lymphadenopathy. If the patient had the primary lesion excised and was to undergo surveillance for regional lymphadenopathy; FNAC could be employed to establish whether there is any lymph node disease. It has come to consensus that the result will be significant when it is positive but require further evaluation when it is negative. (B/III)

Modified inguinal lymphadenectomy (46) (47) (48) is not recommended as a first line management for lymph nodes disease. The consensus is that if the lymph nodes were indeed involved, the usual radical surgery should be advocated. (B/III)

Prediction of regional LN status

Regional lymph node status is an important prognostic indicator in carcinoma of the penis. 5 year survival in patients without lymph node involvement ranges from 71 to 95 % , while for those with lymph node involvement , the range is 28 ? %. (49) (50) (51) (52) (B/III)

By identifying factors predictive of lymph node involvement, we aim to avoid the morbidity of unnecessary lymphadenectomy in those unlikely to benefit, and improve the survival outcome in-patients who are likely to benefit from lymphadenectomy.

75- 100 % of poorly differentiated tumors would have regional lymph node involvement, compared with 12-50 % in well to moderately differentiated tumors. (53) (54) (55) (B/III)

Tumors involving the corpora are more likely (61 ?%) to involve lymph nodes . Tumors not involving the corpora are associated with 5 ? 11 % incidence of lymph node involvement.(56) (57) (B/III)

Others factors identified as having a positive association with regional lymph node involvement include :

Lymphatic & venous embolisation , tumor thickness ( > 5mm) , and size (T stage,as according to UICC TNM 1978).(58) (59) (C/IV)

It is advocated that the degree of differentiation and depth of invasion should be taken into account in the algorithm for treatment of regional lymph nodes. (60) (54) Based on these same factors , a modification to the UICC TNM staging has also been proposed (53), but this has not been widely accepted in current practice and the consensus suggested that this modified staging will need further evaluations before accepting it. (GPP)

Metastasis ( M )

For diseases less than a T2 G2 ?chest X-ray ( CXR ), liver function test ( LFT ) and serum calcium level is sufficient as screening for metastatic disease. (GPP)

Anything primary lesion that is more than T2G2, then CT pelvis and bone scan would be useful.

Again the role of using superparamagnetic iron oxide in MRI for detection of liver metastases requires further evaluation. (61) (51) (62

Surgery for the primary tumor

Penectomy, be it partial or total, has long been regarded as the standard surgical therapy for local control of carcinoma of the penis. Local recurrence in the published literature ranges from 0 to 5%. (56) (63) (64).

The standard margin of resection has traditionally been 15 to 25 mm. However, there is no currently any data to support this figure. Furthermore, it is well known that aggressive local surgery may lead to difficulty in voiding and sexual dysfunction. In a small series, a more conservative margin of 10 mm has been proposed. (65)

In view of the lack of studies with large number of patients on the margin of resection, it is currently recommended that the standard practice of 15 to 25 mm be followed. (GPP)

Conservative surgery is defined as an operation that completely excises the primary tumor with adequate tumor-free margins while preserving satisfactory form and function of the involved organ. (66) Because of the associated morbidity of partial or total penectomy, conservative therapy might be considered in selected patients.

Patient preference has been the strongest indication for conservative surgery. (66) The psychological issues of genital (penile) surgery must be recognized. Conservative surgery offers preservation of body image and improved quality of life. Patients treated with partial or total penectomy had a worse outcome with regard to sexual function than patients treated conservatively. In one study, majority gave priority to higher long-term survival, but some would choose treatment with lower long-term survival to increase the chance of remaining sexually potent. (67)

Small distal tumors could be treated with conservative surgical therapy such as circumcision, local excision, Mohs micrographic surgery or laser surgery. (68) (GPP)

Various conservative therapies offer equally effective results in low stage disease. (69) (GPP)

Penis-conserving therapy might be considered for all tumor <2cm and well differentiated tumors < 4cm. (70) However, penis conservation in a T3 tumor should not be attempted. (69) (B/III)

Premalignant lesions provide the clearest indication for organ-sparing surgery. (71) (66) (B/III)

Conservative surgery may be appropriate in the patient who is elderly or with comorbidity where longevity is compromised and radical surgery carries more significant perioperative morbidity and mortality. Patients likely to die of distant disease should be offered conservative surgery for palliation as necessary. (66) (GPP)

Patient preference has been the strongest indication for conservative surgery. (66) The psychological issues of genital (penile) surgery must be recognized. Conservative surgery offers preservation of body image and improved quality of life. Patients treated with partial or total penectomy had a worse outcome with regard to sexual function than patients treated conservatively. In one study, majority gave priority to higher long-term survival, but some would choose treatment with lower long-term survival to increase the chance of remaining sexually potent. (67)

Small distal tumors could be treated with conservative surgical therapy such as circumcision, local excision, Mohs micrographic surgery or laser surgery. (68) (GPP)

Various conservative therapies offer equally effective results in low stage disease. (69) (GPP)

Penis-conserving therapy might be considered for all tumor <2cm and well differentiated tumors < 4cm. (70) However, penis conservation in a T3 tumor should not be attempted. (69) (B/III)

Premalignant lesions provide the clearest indication for organ-sparing surgery. (71) (66) (B/III)

Conservative surgery may be appropriate in the patient who is elderly or with comorbidity where longevity is compromised and radical surgery carries more significant perioperative morbidity and mortality. Patients likely to die of distant disease should be offered conservative surgery for palliation as necessary. (66) (GPP)

There is possible failure in either controlling local disease or preserving function of the organ. Local control rate following penis-conserving surgery has been lower than that for partial or total penectomy. (69) (72)

Meticulous and regular follow-up is therefore mandatory to salvage local recurrence, most of which are within 2 years of follow-up. (70) (73) (72) (B/III) However, recurrence may occur at greater than 10 years of follow-up. (74)

Because recurrence rates are higher with conservative treatments, salvage therapy becomes important. (70) With appropriate salvage, there was no difference in the disease-specific survival between 2 groups. (72)

In the male, conservative surgery should preserve penile length for upright voiding and sexual function. However, if these objectives are not met because of technical considerations of excising the tumor with clear margins, the patient is exposed to an increased risk of recurrent disease with no benefit. (66)

Small lesions of prepuce have been treated with circumcision alone; however, recurrence rates as high as 50% have been reported. (68) (GPP)

This preserve more penile length, but has recurrence rates up to 50%. (68) (GPP)

Effective therapy have been achieved with CO2 / Nd:YAG laser for superficial tumours. (75) (76) (77) (78) This procedure can be considered for conservative treatment of wide or multiple superficial lesions of the glans penis. With aggressive laser therapy, excellent cosmetic results and low local recurrence (11.4%) could be achieved. (78) PENIN and Stages Tis and Ta tumours may be effectively treated with CO2 or KTP/532 laser. Superficially invasive Stage T1 carcinoma is best treated with the more penetrating Nd:YAG or KTP lasers. (78) However, laser therapy in deeply invasive SCC T2 has universally failed to control the local disease. (79) (B/III) The limitations of laser therapy are in the extremely obese patient, immunosuppressed patients and those patients on anticoagulant therapy.

Cryosurgery preserves penile function, offers excellent cosmetic results, and it could be an outpatient treatment. (80) Cryosurgery is effective for T1-2, N0 M0 penile tumor. (81) (GPP)

Topical 5FU cream might be the preferred initial treatment in most patients with carcinoma-in-situ. (82) (83) (84) (85) (B/III)

Local excision as opposed to conventional penectomy, results in unacceptably high local recurrence rates. (86) Mohs micrographic surgery was originally developed for excision of dermatological lesions and attempts to excise the cancer under total microscopic control, yet preserving maximal amount of normal tissue (87). The original technique has been modified and changes included a fresh-tissue technique and the tissues are sliced horizontally rather than vertically, which have been found to improve the precision of localizing residual tumor (88).

Mohs micrographic surgery was applied to carcinoma of the penis (89). In 25 patients with at least 5-year follow-up, local control was achieved in 23 patients (92%). The 2 failures involved lesions of 3.4 and 4.0 centimeters respectively. Metastases were recorded in 17 patients (68%).

Similar results were reported by Brown (90). However, there were only 11 cases of squamous cell carcinoma and 3 were lost through follow-up and 4 developed metastases.

Based on current literature, Mohs micrographic surgery seems to be a reasonable technique for small localized carcinoma of the penis provided the surgeon and supporting staff are well versed in this technique. (87) (89). (B/III)

Treatment Of Inguinal Lymphadenopathy In Penile Carcinoma

The treatment algorithm depends on the stage and grade of the primary tumor as well as the presence or absence of palpable groin nodes.

Despite the presence of clinically palpable inguinal lymph nodes and histologically proven inguinal metastasis, treatment with lymphadenectomy results in a 20-50% 5-year disease-free survival.(91). However not all enlarged inguinal lymph nodes are metastatic nodes. Subjecting all patients with palpable inguinal lymph nodes to lymphadenectomy may result in over-treatment and unnecessary morbidity.

Whether the inguinal lymph nodes are palpable or not, the primary tumor should be treated accordingly first. (GPP)

If the inguinal lymph nodes are enlarged at presentation, a course of antibiotics is given in the hope that inflammatory changes will resolve. The inguinal nodes are reassessed four to six weeks later by clinical palpation, which has been noted to be practical and acceptably accurate. (GPP)

Most inguinal nodes that persist are metastatic in nature (91) and should then be subjected to lymphadenectomy. This is usually advocated to be done 4 to 6 weeks (92) after the treatment of the primary tumour. By then the pathological stage and grade would have been known also and this information may help in deciding on further surgery.

Whether the palpable nodes are unilateral or bilateral, it is advocated that a bilateral lympadenectomy be done due to the fact that 50 % of the lymphatics have cross-over drainage. The radical lymphadenectomy entails the removal of both the superficial and deep inguinal lymphatic chains. There is currently no proven advantage in removing the pelvic nodes. There are no pelvic node positive patients who are inguinal node negative. The presence of metastatic pelvic lymph nodes usually denote a grave prognosis. (B/III)

In patients with clinically negative inguinal examinations on presentation, there is the controversy of whether a lymphadenectomy should be performed on a prophylactic basis. There is the potential survival benefit of early treatment by removing micrometastasis while it is still curable versus the surgical complications of an extensive operation.

Current available evidence revealed that prophylactic lymphadenectomy should be undertaken if the primary tumor is poorly differentiated or the primary tumor is a T2 tumor or greater. (93) (94) (95) Otherwise surveillance of the inguinal region with close follow up is a reasonable option. (B/III)

The original description for the template for radical inguinal lymphadenectomy was based on an anatomical study by Daseler. The boundaries are: superiorly: anterior superior iliac spine to external inguinal ring; laterally: line from anterior superior iliac spine for approximately 20 cm; medially: line from public tubercle for approximately 15 cm; and inferiorly: line joining medical and lateral boundaries.

However, the surgery carries a high morbidity and a mortality rate of 3%. Major complications include disabling lymphadema (20 ?%), seroma (15 ?%), skin flap necrosis (14 ?%) and wound infection (10 ?%.) (96) (97) (64) (98) (99) (100)

In view of the high complication rate and the inaccuracy of clinical staging of inguinal lymph nodes, Catalona proposed a modified template for inguinal dissection. The boundaries are: superiorly: line between spermatic cord and external inguinal ring; laterally: lateral edge of femoral artery; medially: adductor longus; and inferiorly: fascia lata just distal to fossa ovalis. (101)

Further evidence to support the role of modified inguinal lymphadenectomy includes studies on the anatomical lymphatic drainage of the penis. Riveros did not find any direct connection from the penis to the deep inguinal lymph nodes (102). Other reports have shown that deep inguinal lymph nodes are positive for disease only when the superficial inguinal lymph nodes are involved too. Pelvic spread without inguinal lymph node involvement had not been reported.

Three subsequent articles on modified inguinal lymphadenectomy were published. Two supported its usage (103) (104) and one found it unreliable (105). All 4 studies involved a small number of patients (5 to 13) and, with the exception of ColbergⳠpaper, had short follow-up periods.

Given these limitations, the role of modified inguinal lymphadenectomy for the management of positive inguinal lymph node is not clearly established. However, it may be recommended for prophylactic lymphadenectomy in patients especially when the radical surgery may be associated with higher morbidity in these patients. However, if the superficial lesion is positive, then a formal radical surgery may be recommended (GPP)

Radiotherapy

Local radical radiotherapy is an alternative treatment to surgery in selected Stage T1 or T2 clinical node negative tumours. Either brachytherapy or teletherapy or a combination of both can be used. There is obvious advantage of organ preservation and cosmesis and salvage surgery is possible. (106) (107) (108)

Post-operative radiotherapy after a partial or complete amputation may be offered in selected patients. (109) (110)

Local palliative radiotherapy can be applied to inoperable tumors and in patients who are medically unfit for palliative surgery. Inoperable groin nodes can also be approached with palliative radiotherapy. (111) (B/III)

Post-operative radiotherapy for the groin is practiced in selected cases but itⳠ impact is limited and morbidity is severe. (112)

Appendix A

Appendix B

Algorithm for Management of Carcinoma of Penis

* denotes areas of controversies that need further studie

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