The challenge of germ cell tumour therapy in dialysis and transplantation

Email: cally.dean{at}bsuh.nhs.uk

Sir,

We report an unusual pattern of recurrent seminoma and highlight the choices in curative treatment in the context of peritoneal dialysis and transplantation. A 53-year-old man with end-stage renal failure secondary to autosomal dominant polycystic kidney disease on continuous ambulatory peritoneal dialysis was noted to have an enlarged right testicle. Investigation revealed a stage I classical seminoma entirely confined to the testis and he underwent orchidectomy. He received adjuvant radiotherapy to a para-aortic strip (20 Gy in 10 fractions). Human chorionic gonadotrophin (ßHCG) and {alpha}-fetoprotein were negative and there was no evidence of lymphadenopathy or of metastatic spread on CT. Two years later, with no evidence of tumour recurrence after repeated staging investigations, he received a cadaveric renal transplant. Immunosuppression was with basiliximab, followed by tacrolimus and prednisolone. Four months post-transplant, a sudden rise in ßHCG to 199 iU/l was noted. A CT scan of the chest, abdomen and pelvis was reported as normal, and he had a normal ultrasound scan and biopsy of his remaining testicle. However, a positron emission tomography (PET) scan revealed an intense focus of uptake in the left supraclavicular fossa (Figure 1). A high resolution CT and fine needle aspiration of a tiny lesion in this area showed recurrent seminoma. He was given chemotherapy with etoposide, bleomycin and carboplatin in three cycles, followed by local radiotherapy. Two years later he is well with serum creatinine of ~100 µmol/l, with no evidence of tumour recurrence.



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Fig. 1. Fluorodeoxyglucose PET scan.

 
Germ cell tumours are the most common cancers in young men and are highly amenable to treatment, with cure rates of ~90%. Testicular neoplasms are 20–50% more prevalent amongst immunosuppressed patients when compared with controls. Low levels of ßHCG are seen in only 10–25% of seminomas. After orchidectomy and radiotherapy a 1–2% relapse rate is quoted. Testicular neoplasms are more prevalent among organ transplant recipients. There is a lower recurrence rate in renal compared with cardiac allograft recipients [1], suggesting that tumour surveillance is impaired proportionally to the degree of immunosuppression. This patient had a very unusual presentation for his seminomatous recurrence, with the rise in ßHCG, which could be explained simply by an increase in tumour load. The focus of recurrence was at a distant site from the primary cancer, so it is possible that there were further seeded metastases that were not picked up by the imaging but that contributed to the tumour marker concentration at the time of recurrence. The small proportion of producing ßHCG seminomas may behave clinically as non-seminomatous germ cell tumours (NSGCT). The threshold value many clinicians use to suggest NSGCT is a ßHCG level of 200 iU/l [2].

The dramatic rise in ßHCG prompted careful diagnostic surveillance scans, which failed to detect recurrence at this stage. It was only with PET scanning that we localized the metastatic area. A higher sensitivity (70 vs 40%) and specificity (100 vs 78%) has been reported for PET vs CT scanning, with ~100% specificity and positive predictive values for metastases >5 mm with PET. However, it is not reliable in differentiating between fibrosis and residual tumour mass [3].

There is a paucity of data on the effects of radiotherapy on the peritoneum, but what is available suggests it can cause an increase in permeability of the peritoneum to water causing a loss in ultrafiltration or haemoperitoneum [4]. This did not occur in our patient and his PD prescription remained unchanged throughout his treatment.

Cisplatin is the most effective agent against seminomas and metastatic disease, and there are reports of successful treatment of renal transplant recipients with this drug [5]. However, due to the well documented nephrotoxicity of cisplatin, we chose to use carboplatin, and this caused no problems with graft function. The sequelae of chemotherapy on a transplanted kidney is not necessarily seen immediately and cases of renal deterioration up to 6 years post chemotherapy have been reported, but after time it becomes difficult to identify whether the chemotherapy agent is the culprit. We also considered renoprotection using sodium thiosulphate and N-acetylcysteine [6], but were worried about reducing the anti-tumour properties of the drugs.

In summary this patient with a germ cell tumour had no PD problems after standard radiotherapy, but had an unusual presentation of recurrence. PET scanning is strongly suggested if recurrence is suspected. Transplantation did not interfere with modified standard chemotherapy, with a good outcome from tumour and transplant.

Conflict of interest statement. None declared.

Caroline Dean, David Bloomfield and Stephen Holt

Brighton and Sussex University Hospitals NHS Trust Royal Sussex County Hospital Brighton BN2 5BE, UK

References

  1. Kauffman HM, McBride MA, Delmonico FL. First report of the United Network for Organ Sharing Transplant Tumor Registry: donors with a history of cancer. Transplantation 2000; 70: 1749–1751[CrossRef]
  2. Swartz DA, Johnson DE, Hussey DH. Should an elevated human chorionic gonadotrophin titre alter therapy for seminoma? J Urol 1984; 131: 63–65[ISI][Medline]
  3. Albers P, Bender H, Yilmaz H, Schoeneich G, Biersack HJ, Mueller SC. Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors. Urology 1999; 53: 808–811[CrossRef][ISI][Medline]
  4. Hutchison AJ, Boulton HF, Gokal R. Effect of radiotherapy on peritoneal function in CAPD. Nephron 1993; 64: 136–138[ISI][Medline]
  5. Bokemeyer C, Kollmannsberger C, Stenning S, Hartmann JT, Horwich A, Clemm C et al. Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials. Br J Cancer 2004; 91: 683–687[ISI][Medline]
  6. Leitao DJ, Blakley BW. Quantification of sodium thiosulphate protection on cisplatin-induced toxicities. J Otolaryngol 2003; 32: 146–150[ISI][Medline]




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