Radiotherapy for the Management of Regional Lymph Node Metastases

Inguinal and pelvic lymph node metastases are a frequent problem in the management of penile cancer. At the time of diagnosis, 20-50% of patients have palpable lymph nodes with about 50% of these representing inflammatory adenopathy and another 50% representing metastases. Approximately 20% of the patients without palpable inguinal nodes have occult metastases.

Elective irradiation of clinically uninvolved lymph node regions has proven to be an effective policy in many tumors, especially in squamous cell carcinoma. The concept is successfully applied in head and neck tumors, cervical cancer, anal cancer, vulvar cancer, etc. In vulvar cancer with positive groin nodes, radiation of pelvic nodes proved superior to pelvic node dissection in a randomized trial.39 However, a randomized trial performed by the Gynaecological Oncology Group in patients with squamous carcinoma of the vulva with nonsuspicious inguinal nodes comparing groin dissection and groin irradiation in conjunction with radical vulvectomy was closed prematurely because of an excessive number (18%) of groin relapses in the groin radiation arm.40 Detailed analyses of the results revealed that the radiation protocol as employed in the study was inappropriate and possibly responsible for the poor results.41

In penile cancer, elective radiotherapy has never widely been used or gained acceptance. In the EAU Guidelines a surveillance programme is strongly advised in low-risk patients. In intermediate-risk patients a modified inguinal lymphadenectomy or alternatively a dynamic sentinel lymph node procedure is recommended. In patients at high risk of nodal involvement a modified or radical lymphadenectomy is always advised. Elective radiotherapy is not recommended based upon disappointing results in two nonrandomized studies. However, one of these studies does not at all address the question of whether elective radiation is effective.42 The study reports upon 120 patients with lymph node involvement in the groin irradiated preoperatively. It is concluded that radiation is highly effective in patients with mobile lymph nodes larger than 4 cm with only 8% of lymphadenectomy specimens showing perinodal infiltration and only 3% of such patients having postoperative groin recurrences. In a previous publication by the same authors they reported in the same patient category an incidence of 33% perinodal infiltration and 19% groin recurrences in the absence of preoperative radiation.19 Furthermore the authors report that none of the patients with positive pelvic lymph nodes survived for 5 years, despite lymphadenectomy followed by pelvic and/or para-aortic irradiation.

In a further publication cited in the EAU guidelines a group of 27 patients with N0 and N1-2 carcinoma treated with bilateral groin dissection is compared with a group of 18 patients with N0 and N1-2 treated with radiotherapy to the groin.43 During follow-up two relapses occurred after radiation compared to only one after surgery. Survival rates in the N0 group was superior in the surgical group compared with the irradiated group. It can be concluded that this nonrandomized study is far from being a proof against the effectiveness of elective radiation. In penile cancer, the role of elective radiation remains unclear but based upon well-established effectiveness in other squamous carcinoma sites deserves to be explored.

The place of adjuvant postoperative radiation is also surrounded by controversy. The incidence of inguinal recurrence in patients with inguinal lymph node metastasis treated with lymphadenectomy varies between 25% and 77%.11,44,45 Adjuvant radiation to the inguinal lymphatic area has been advocated by some, if histopathological examination of the inguinal specimen revealed more than one metastatic lymph node and/or extran-odal extension. Chen reported that postoperative groin irradiation reduced the inguinal recurrence rate from 60% (three recurrences in five patients) to 11% (one recurrence in nine patients).46 However, larger series confirming this benefit are still lacking.

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