36-year-old man with abdominal pain and retroperitoneal lymphadenopathy

The patient was a 36-year-old man with a limited past medical history who presented with complaints of abdominal pain. The pain had an achy sensation — ranked two out of 10 in intensity — radiating down toward his groin. The patient reported taking some magnesium citrate two nights prior to his initial presentation without much relief in his pain. He had no nausea or emesis. He had no fevers or chills. He said he had lost approximately 25 lb in the previous three months, but he had been dieting and trying to lose weight. He denied any chest pain or cough. He had no rashes on his skin. He had no changes in urinary symptoms, urgency or micturition, and also did not have any changes in his bowel habits. The remainder of his review of systems was negative.

Anne H. Blaes

The patient presented to the emergency department where a CT scan of his abdomen was performed revealing retroperitoneal lymphadenopathy. The largest lymph node on the left side measured 2.9 cm × 4.7 cm and the largest on the right measured 7.4 cm × 4.4 cm × 6.8 cm. Subsequently, a biopsy was performed revealing a pure seminoma.

Further studies revealed the following: CT of the chest was negative for evidence of metastatic disease. A PET CT revealed uptake in the previously identified retroperitoneal lymph node beds with SUV of 16 and 11, but no additional PET positive areas in the body. The patient has a normal head CT. A subsequent testicular ultrasound revealed a 0.5 cm × 0.5 cm × 0.4 cm well circumscribed mass lesion in the right testicle.

Past medical history: Prior knee surgery for a torn meniscus.

Medications: None.

Allergies: No known drug allergies.

Family history: Mother, maternal grandmother and paternal grandfather all had type 2 diabetes. Maternal grandfather and maternal grandmother had a history of cerebrovascular accident. No history of malignancy.

Social history: He had been in a monogamous homosexual relationship for the past decade. He had no tobacco use or illicit drug use. He rarely consumed alcohol.

Physical examination: vital signs: Temperature is 97.8 °, pulse 78, respirations 18, blood pressure 122 mm Hg/74 mm Hg, O₂ saturations are 98% on room air. HEENT: Head examination is normocephalic, atraumatic, extraocular movement are intact. PERRLA: no pharyngeal erythema or exudate. Neck: Supple, no carotid bruits. No lymphadenopathy noted. Respiratory: Chest is clear to auscultation bilaterally, no wheezing, rales or rhonchi. Cardiac: S1, S2, regular rate and rhythm. No S3, S4 appreciated. No murmurs, gallops or rubs noted. GI: The patient has a mild tenderness to deep palpation of the right lower quadrant. Bowel sounds are positive and active in all four quadrants, no rebound tenderness. No rigidity and no severe tenderness. GU: He did not have any testicular enlargement. The patient did not have any scrotal edema. There were no palpable masses appreciated.

Laboratory: WBC 7.2, hemoglobin 14.3, platelets are 275,000. Kidney function was normal. Alpha-fetoprotein was < 1.5, beta human chorionic gonadotropin < 3, and LDH was 630, which is within normal institutional limits.

What is the best way to manage this patient?

A. Surgical resection of the testicular mass with retroperitoneal lymph node dissection.

B. Orchiectomy followed by radiation therapy.

C. Orchiectomy followed by chemotherapy with cisplatin and etoposide.

D. Orchiectomy followed by high-dose chemotherapy and stem cell transplantation.

Case Discussion

This patient is a 36-year-old man with stage II seminoma involving the right testicle and the retroperitoneal lymph nodes. Although the definition of bulky disease can vary, it appears this patient has stage II bulky seminoma. Testicular cancer is the most common malignancy affecting men aged 15 to 35 years. It is a highly treatable disease, even in the presence of metastatic disease. Eighty percent of patients with seminomatous testicular cancer are diagnosed with stage I disease, while 15% present with metastatic disease involving the infradiaphragmatic lymph nodes (stage II); the remaining 5% present with disseminated disease involving either the brain, liver, lungs or bones.

In this particular case, the treatment of choice would be orchiectomy followed by chemotherapy with etoposide and cisplatin. In the case of stage II disease, the treatment of testicular cancer involves orchiectomy followed by additional therapy. For nonbulky disease — in which case the lymph node with the largest diameter is less than 5 cm to 7 cm — many patients have been treated with radiation therapy alone after orchiectomy. For patients treated with low-dose radiation therapy to 35 Gy involving the paraaortic and ipsilateral pelvic lymph nodes followed by a boost to the involved lymph nodes, five-year disease free survival rates of 85% to 94% can be achieved. As a result, it would seem that radiation therapy after orchiectomy could be an alternative choice if the retroperitoneal lymph nodes were smaller in size.

However, for patients with bulky lymph node involvement such as our patient, it is more optimal to consider systemic chemotherapy. Single-agent chemotherapy has been tried in this setting with poor outcomes. The German Testicular Cancer Group treated 108 patients with three to four cycles of carboplatin as an alternative to radiation therapy. In this case, patients initially responded, but 19% relapsed. As a result, single-agent carboplatin is not recommended. For patients with bulky lymph nodes measuring at least 5 cm to 7 cm in diameter at presentation, treatment with radiation therapy alone results in five-year disease free survival rates of 65%. Relapse rates are as high as 50%. Although the subsequent salvage rates are considered high, leading to overall survival rates of up to 91% at five years, adjuvant radiation therapy alone in patients with bulky disease is not considered optimal.

Cisplatin-based combination chemotherapy appears to be the most effective treatment in this setting. In one study of 130 patients with stages II, III, or IV disease, patients were randomly assigned to four cycles of cisplatin and etoposide as compared with carboplatin. With a median follow-up of 4.5 years, the progression free survival was 81% vs. 71% with carboplatin, and the three-year overall survival was 89% vs. 84% with carboplatin. Other studies have reported similar outcomes. In some cases, bleomycin has been studied in combination with etoposide and cisplatin; however, given the toxicity of bleomycin, its use is often reserved for patients with nonseminomatous tumors and high-risk features.

High-dose chemotherapy with stem cell rescue is typically reserved for metastatic testicular cancer tumors that have relapsed or have not responded to initial platinum-based chemotherapy with disease free survival rates of approximately 70%. Retroperitoneal lymph node dissection is typically reserved for patients with nonseminomatous germ cell tumors.

In our particular case, the patient was treated with four cycles of etoposide and cisplatin. He tolerated the treatment without significant toxicities. He had a PET scan following therapy that revealed a residual 2 cm mass with no SUV uptake. Based on the results of the SEMPET study that resulted in a positive predictive value of 100% and a negative predictive value of 96%, the patient was observed. Postchemotherapy residual masses usually represent fibrosis, and given the negative PET scan, the patient was monitored without any additional therapy.

Anne H. Blaes, MD, is an Assistant Professor at the University of Minnesota and a member of the HemOnc Today Editorial Board.

For more information:

• De Santis M.J Clin Oncol. 2004;22:1034-1039.
• Einhorn LHN Engl J Med. 2007; 357: 340-348.