Susanna Alexander
Case history
A 66-year-old man presented to the emergency department with a 4-week history of increasing abdominal pain and fatigue. He was having conservative treatment for a diabetic foot ulcer under the vascular surgery team. He had lost 10kg in weight in the last 3 months. Clinical examination revealed an abdominal mass and palpable left supraclavicular lymphadenopathy. He had a CT scan of the chest and abdomen (Fig. 17.1). Biopsy from supraclavicular nodes showed a poorly differentiated neoplasm composed of monotonous sheets of pleomorphic large cells having abundant cytoplasm and hyperchromatic nuclei. The abnormal cellular population was strongly immunore-active for placenta-like alkaline phosphatase (PLAP), OCT4, and CD117.
Fig. 17.1
Questions
1. What do the CT scans (Fig. 17.1) show?
2. How would you interpret the immunohistochemistry results?
3. What further investigations would you complete?
Answers
1. What do the CT scans (Fig. 17.1) show?
The CT scans show a large retroperitoneal mass surrounding the aorta (A). There is contiguous left common iliac and left external iliac lymphadenopathy (B). No other mass or destructive bone lesions were seen in the images. The differential diagnoses are lymphoma and germ cell tumour.
2. How would you interpret the immunohistochemistry results?
Immunohistochemistry shows this to be a seminoma. Seminoma is composed of a population of monotonous cells, and a very high proportion (98%) of seminomas show diffuse staining with antibodies to PLAP. Abnormal cells in testicular carcinoma in situ also stain with PLAP. CD117/c-KIT is specific for seminoma and positive in the majority of cases, but is rarely positive in embryonal carcinomas. OCT3/4 is a nuclear marker of classical seminoma and embryonal carcinoma. It has excellent sensitivity and specificity for these two tumours, and can be effectively used as the ‘screen’ for these neoplasms, especially when dealing with a metastatic tumour of unknown origin.
3. What further investigations would you complete?
A testicular ultrasound is needed to confirm the presence of a testicular mass even if there is clinically evident tumour. It will also assess the contralateral testis.
Serum tumour markers are prognostic factors when measured at diagnosis, and include beta human chorionic gonadotropin (β-hCG), α-fetoprotein (AFP), and lactate dehydrogenase (LDH). AFP and/or β-hCG are elevated in 80–85% of men with non-seminomatous germ cell tumours (NSGCTs). In contrast, serum β-hCG is elevated in fewer than 25% of seminomas, and AFP is not elevated in pure semi-nomas. LDH is elevated in 80% of patients with advanced testicular cancer and is important in deciding the prognostic group according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification (International Germ Cell Cancer Collaborative Group 1997). Tumour markers are also important in monitoring the response to treatment and detecting recurrence.
Testicular US showed a 1.6cm mass in the lower pole of the left testis which displayed course hypo-echogenicity and scattered microcalcification in keeping with a primary testicular tumour. The right testis was normal. The serum tumour markers were hCG 111IU/L (normal < 5IU/L), AFP < 1.0kU/L (normal 0–10kU/L), and LDH 931U/L (normal 125–243U/L).
Question
4. How would you treat this man?
Answer
4. How would you treat this man?
All patients with a testicular tumour should undergo an orchidectomy with division of the spermatic cord at the internal inguinal ring. In patients with disseminated disease and life-threatening pulmonary metastases, chemotherapy should be initiated immediately and orchidectomy delayed until clinical stabilization or completion of chemotherapy. In view of disseminated disease, this man should be considered for immediate chemotherapy.
Questions
5. If he needs chemotherapy, outline your pre-treatment assessment.
6. What is his estimated survival?
Answers
5. If he needs chemotherapy, outline your pre-treatment assessment.
Since this man has a metastatic germ cell tumour with good prognosis (seminoma with no non-pulmonary visceral metastases and normal AFP), the standard treatment option would be three cycles of BEP (bleomycin, etoposide, and cisplatin) chemotherapy. In patients for whom bleomycin is contraindicated or not advisable, four cycles of etoposide and cisplatin chemotherapy can be given instead. The MRC/EORTC TE20 study (de Wit et al. 2001) tested the equivalence of three versus four cycles of BEP and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. The study showed that three cycles of BEP with etoposide 500 mg/m2 administered in 3 days was as effective as other regimens.
An alternative option in patients with significant comorbidities would be carboplatin chemotherapy given at area under the curve (AUC) 10 at 3-weekly intervals for a total of four cycles. This regimen was reported to be well tolerated, and 92% of patients were disease free in long-term (Oliver et al. 2004).
Pre-chemotherapy assessment includes the following:
♦ Record the WHO performance status, current height, weight, and body surface area.
♦ FBC, U&Es (including magnesium and calcium) and serum creatinine, liver function tests, AFP, HCG, and LDH.
♦ Consider formal measurement of creatinine clearance (creatinine clearance should ideally be >60ml/min) in patients with low surface area using either 24-hour urine collection or chromium-51 labelled ethylene diamine tetra-acetic acid (15Cr-EDTA) measurement.
♦ Auditory assessment and pulmonary function tests including transfer factor.
♦ Informed consent.
♦ Where appropriate, discuss fertility issues and arrange sperm storage if necessary.
♦ Patients should have the support of a specialist nurse for holistic assessment.
6. What is his estimated survival?
The estimated 5-year PFS is 82% and the OS is 86% in patients with good-prognosis seminoma.
In view of his comorbidity, he proceeded with four cycles of AUC 10 carboplatin without initial orchidectomy. Re-staging showed normal serum markers and complete disappearance of the left supraclavicular node on CT scan. The post-chemotherapy abdominal CT scan is shown in Fig. 17.2.
Fig. 17.2
Questions
7. What do the scans in Fig. 17.2 show?
8. What treatment would you recommend next?
Answers
7. What do the scans in Fig. 17.2 show?
The CT scan shows residual para-aortic and left pelvic lymphadenopathy.
8. What treatment would you recommend next?
He is advised to have an orchidectomy and is recommended to have a 18FDG PET scan to confirm or refute active disease and therefore to decide between watchful waiting and active treatment.
Though there is no established role for 18FDG PET in the staging of germ cell tumours or the re-staging of patients with non-seminomatous germ cell tumours after chemotherapy, it is recommended in patients with seminoma who have any residual disease at least 6 weeks after chemotherapy to identify active tumour. The SEMPET trial reported that 18FDG PET correctly identified all cases of active tumour in residual lesions >3cm and 95% of active tumour in lesions of <3cm (specificity of 100% and sensitivity of 80%) (De Santis et al. 2004).
Histopathology after orchidectomy showed testis with extensive fibrous scarring and scattered chronic inflammatory cells, including pigment-laden macrophages, and atrophic seminiferous tubules suggesting post-chemotherapy scarring. The PET scan is shown in Fig. 17.3 (and in colour plate section).
Fig. 17.3 (See also colour plate section)
Questions
9. What does the PET scan in Fig. 17.3 show?
10. What is the follow-up management?
Answers
9. What does the PET scan in Fig. 17.3 show?
The residual para-aortic and left pelvic adenopathy accumulates only background levels of 18FDG, suggesting a metabolic complete response.
If PET scan is not available, repeat CT scan is advised at 2 and 4 months in patients with > 3cm residual tumour after chemotherapy for seminoma to ensure continuing regression of the mass.
10. What is the follow-up management?
The patient should have regular follow-up to detect treatable recurrent disease. The recommended minimum follow-up in metastatic testicular cancer includes 3-monthly physical examination, tumour marker estimation and chest X-ray, and 6-monthly abdomino-pelvic CT for 2 years, 6-monthly physical examination, tumour marker estimation, and chest X-ray for 3 years, and annual physical examination, tumour marker estimation, and chest X-ray thereafter.
Follow-up of this case
The patient continues to be well with no evidence of progression or recurrence 12 months after his orchidectomy.
Further reading
Albers P, Albrecht W, Algaba F, et al. EAU guidelines on testicular cancer: 2011 update. European Urology 2011; 60: 304–319.
De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. Journal of Clinical Oncology 2004; 22: 1034–1039.
International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. Journal of Clinical Oncology1997; 15: 594–603.
Oliver RTD, Shamash J, Powles T, Somasundram U, Ell PJ. 20 year phase 1/2 study of single agent carboplatin in metastatic seminoma: could it have been accelerated by 72 hour PET scan response? Journal of Clinical Oncology ASCO Meeting Proceedings 2004; 22: 4763 (abstract).
Sohaib AS, Koh W and Husband JE. The role of imaging in the diagnosis, staging and management of testicular cancer. American Journal of Roentgenology 2008; 191: 387–395.
de Wit R, Roberts JT, Wilkinson PM, et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. Journal of Clinical Oncology 2001; 19: 1629–1640.