Recent developments in germ cell tumors of the testes

Current Opinion in Oncology

Volumn 20, Issue 3, 2008, Pages 287-293

  Tummala, Mohan K ^a   Hussain, Arif ^a,b,c  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b BALTIMORE VA MEDICAL CENTER   (United States)

^c UNIVERSITY OF MARYLAND   (United States)

Author keywords

Chemotherapy; Genetic studies; Germ cell tumor; Imaging; Nonseminomatous germ cell tumor; Seminoma; Surgery; Surveillance; Toxicity; Tumor marker

Indexed keywords

BIOLOGICAL MARKER; BLEOMYCIN; CARBOPLATIN; CISPLATIN; CYCLOPHOSPHAMIDE; EPIRUBICIN; ETOPOSIDE; GEMCITABINE; IFOSFAMIDE; PACLITAXEL;

CANCER CHEMOTHERAPY; CANCER EPIDEMIOLOGY; CANCER RESEARCH; CANCER STAGING; CLINICAL TRIAL; DIAGNOSTIC IMAGING; FOLLOW UP; GENETIC ANALYSIS; GERM CELL TUMOR; HUMAN; LYMPH NODE DISSECTION; MULTIPLE CYCLE TREATMENT; OTOTOXICITY; PRIORITY JOURNAL; REVIEW; TOXICITY;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CISPLATIN; ETOPOSIDE; HUMANS; LYMPH NODE EXCISION; LYMPH NODES; MALE; NEOPLASMS, GERM CELL AND EMBRYONAL; PROGNOSIS; RETROPERITONEAL SPACE; RISK FACTORS; SEMINOMA; TESTICULAR NEOPLASMS; TUMOR MARKERS, BIOLOGICAL;

EID: 41949132657     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/CCO.0b013e3282f8b064     Document Type: Review

References (34)

1. Sokoloff MH, Joyce GF, Wise M. Testis cancer. J Urol 2007; 177:2030-2041.
2. Bertuccio P, Malvezzi M, Chatenoud L, et al. Testicular cancer mortality in the Americas, 1980-2003. Cancer 2007; 109:776-779.
3. Shah MN, Devesa SS, Zhu K, McGlynn KA. Trends in testicular germ cell tumours by ethnic group in the United States. Int J Androl 2007; 30:206-213. [discussion 213-214].
4. Levi F, Lucchini F, Negri E, et al. Trends in cancer mortality in the European Union and accession countries, 1980-2000. Ann Oncol 2004; 15:1425-1431.
5. Sant M, Aareleid T, Artioli ME, et al. Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study. Eur J Cancer 2007; 43:585-592.
6. Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007; 356:1835-1841. This large study provides convincing confirmatory evidence that earlier orchiopexy decreases risk of subsequent TGCTs in cryptorchid men.
7. Coffey J, Huddart RA, Elliott F, et al. Testicular microlithiasis as a familial risk factor for testicular germ cell tumour. Br J Cancer 2007; 97:1701-1706.
8. Almstrup K, Leffers H, Lothe RA, et al. Improved gene expression signature of testicular carcinoma in situ. Int J Androl 2007; 30:292-302. [discussion 303].
9. Gillis AJ, Stoop HJ, Hersmus R, et al. High-throughput microRNAome analysis in human germ cell tumours. J Pathol 2007; 213:319-328. In addition to the traditional expression profiling of protein-encoding genes, this study demonstrates that microRNA profiling can also provide 'expression signatures' for the different subtypes of GCTs, depending upon their relative differentiation status. Thus, microRNAs can be informative in distinguishing the different GCTs. Their biological relevance in GCT pathogenesis remains to be elucidated.
10. Bartek J, Lukas J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol 2007; 19:238-245. An excellent overview of the DDR network and its relation to tumorigenesis.
11. Bartkova J, Horejsí Z, Sehested M, et al. DNA damage response mediators MDC1 and 53BP1: constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours. Oncogene 2007; 26:7414-7422. Activation of components of the DDR network may serve as a part of an early anticancer barrier. Subsequent inactivation of upstream (e.g., loss of 53BP1/ MDC1) or downstream DDR components (e.g., p53 mutations) can lead to cancer progression in solid tumors. Interestingly, in TGCTs the apparent absence of spontaneous DDR activation may in part account for the low incidence of p53 mutations in these tumors.
12. Fung MK, Cheung HW, Wong HL, et al. MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. Biochim Biophys Acta 2007; 1773:821-832.
13. Santagata S, Ligon KL, Hornick JL. Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. Am J Surg Pathol 2007; 31:836-845.
14. Franco R, Esposito F, Fedele M, et al. Detection of high-mobility group proteins A1 and A2 represents a valid diagnostic marker in post-pubertal testicular germ cell tumours. J Pathol 2008; 214:58-64.
15. Rustin GJ, Mead GM, Stenning SP, et al. Randomized trial of two or five computed tomography scans in the surveillance of patients with stage I nonseminomatous germ cell tumors of the testis: Medical Research Council Trial TE08, ISRCTN56475197 - the National Cancer Research Institute Testis Cancer Clinical Studies Group. J Clin Oncol 2007; 25:1310-1315.
16. Huddart RA, O'Doherty MJ, Padhani A, et al. 18fluorodeoxyglucose positron emission tomography in the prediction of relapse in patients with high-risk, clinical stage I nonseminomatous germ cell tumors: preliminary report of MRC Trial TE22 - the NCRI Testis Tumour Clinical Study Group. J Clin Oncol 2007; 25:3090-3095.
17. de Wit R. Cutting back on computed tomography scan frequency in curative oncology: get the picture. J Clin Oncol 2007; 25:1308-1309.
18. Carver BS, Shayegan B, Serio A, et al. Long-term clinical outcome after postchemotherapy retroperitoneal lymph node dissection in men with residual teratoma. J Clin Oncol 2007; 25:1033-1037. This is the largest series evaluating long-term outcome of patients with metastatic NSGCTs found to have residual teratomatous elements post chemotherapy-RPLND. Among 210 patients evaluated, disease recurred in 30 patients but in-field in only one patient, not only demonstrating the importance of good surgical control within the retroperitoneum but also highlighting the risk for recurrence outside the surgical field despite effective RPLND. Further, 50% of the recurrences were with viable GCT, 17% with teratoma with malignant transformation, and several recurrences occurred beyond 2 years. These data emphasize the need for vigilance in following such patients.
19. Shayegan B, Carver BS, Stasi J, et al. Clinical outcome following post-chemotherapy retroperitoneal lymph node dissection in men with intermediate- and poor-risk nonseminomatous germ cell tumour. BJU Int 2007; 99:993-997. This study underscores the importance of resecting completely residual disease after chemotherapy in intermediate and poor risk patients. Forty eight percentage of the patients in this retrospective analysis also had extra-retroperitoneal disease post chemotherapy. Five-year progression-free probabilities of 70% were achieved after RPLND and resections of other metastatic sites. Interestingly, contrary to other reports, prognosis of patients was not influenced by whether they had intermediate or poor risk disease; conceivably, a greater proportion of men with poor risk disease may not have been included in the analysis if they had rapid disease progression and never underwent RPLND.
20. Carver BS, Shayegan B, Eggener S, et al. Incidence of metastatic nonseminomatous germ cell tumor outside the boundaries of a modified postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol 2007; 25:4365-4369. Despite several limitations, this is a provocative report putting into question the relative efficacy and validity of modified surgical templates in men undergoing post chemotherapy-RPLND.
21. Eggener SE, Carver BS, Sharp DS, et al. Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol 2007; 177:937-942. [discussion 942-943]. This study defines the incidence of extratemplate disease in patients with clinical stage 1 and stage 2A NSGCTs undergoing primary RPLND and found to have pathological stage 2 disease at surgery. The extent of lymph node dissection varies with the different modified templates. The data demonstrate that with more limited dissection, as many as 23% of patients with pathological stage 2 GCT will have disease outside the surgical boundaries.
22. Culine S, Kerbrat P, Kramar A, et al. Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). Ann Oncol 2007; 18:917-924. A direct comparison of BEP x 3 to etoposide/cisplatin x 4 in metastatic good risk GCT. Although underpowered, interesting results with respect to toxicity emerged. Contrary to expectations, BEP x 3 was associated with greater neurotoxicity than etoposide/cisplatin x 4 (any grade,16 vs. 5%, P=0.006). Similar rates of pulmonary toxicity (primarily low grade) were observed between the two regimens, whereas, but not unexpectedly, significantly greater Raynaud's phenomena occurred with BEP x 3 than etoposide/cisplatin x 4 (29 vs. 8%, P=0.0001).
23. de Wit R. Refining the optimal chemotherapy regimen in good prognosis germ cell cancer: Interpretation of the current body of knowledge. J Clin Oncol 2007; 25:4346-4349. Thoughtful and concise commentary on the evolution of three-drug and four-drug combination regimens, including the French GETUG T93BP trial, in metastatic good risk GCT.
24. Motzer RJ, Nichols CJ, Margolin KA, et al. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 2007; 25:247-256. The trial demonstrated no advantage of HDCT over standard BEP x 4 as first-line therapy for poor risk GCT. Subset analysis revealed that the durable 1-year CR rate among the 67 patients with unsatisfactory STM decline after the first two cycles of BEP who went on to HDCT was 61 compared with 34% for patients who remained on standard BEP (P=0.03). Additional validation, however, is required to determine whether patients can be appropriately stratified to standard or HDCT in the first-line setting based on STM decline.
25. Pico JL, Rosti G, Kramar A, et al. A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 2005; 16: 1152-1159.
26. Einhorn LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 2007; 357: 340-348. This report adds to the growing experience with salvage HDCT and highlights the decreasing incidence of treatment-related deaths in more recent series of HDCT. This series included men with recurrent or progressive GCT (81% NSGCTs, 19% seminoma) and excluded those with primary mediastinal NSGCTs or late relapses (>2 years from prior therapies). Although retrospective and only a limited number of patients were treated, activity of HDCT was also demonstrated in the subset of men treated in the third line or later setting and in those with platinum-refractory disease.
27. Lorch A, Kollmannsberger C, Hartmann JT, et al. Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group. J Clin Oncol 2007; 25:2778-2784.
28. Kondagunta GV, Bacik J, Sheinfeld J, et al. Paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol 2007; 25:85-90.
29. Einhorn LH, Brames MJ, Juliar B, Williams SD. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol 2007; 25:513-516.
30. Bedano PM, Brames MJ, Williams SD, et al. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol 2006; 24:5403-5407.
31. Oldenburg J, Kraggerud SM, Cvancarova M, et al. Cisplatin-induced long-term hearing impairment is associated with specific glutathione s-transferase genotypes in testicular cancer survivors. J Clin Oncol 2007; 25:708-714. This is the largest study to date examining association between GST polymorphisms and cisplatin-induced ototoxicity. Specifically, the authors showed that 21/30 (70%) cisplatin-treated patients who expressed GSTT1, GSTM1 and 105Ile/105Ile GSTP1 had impaired hearing compared to 68/143 (48%) (P=0.004) patients with other GST genotype combinations, and 16/20 (80%) patients expressing GSTT1, GSTM1 and 105Val/105Val GSTP1 had no impairment in hearing compared to 68/153 (44%) patients with other genotypes (P=0.009).
32. Fossa SD, Gilbert E, Dores GM, et al. Noncancer causes of death in survivors of testicular cancer. J Natl Cancer Inst 2007; 99:533-544.
33. van den Belt-Dusebout AW, de Wit R, Gietema JA, et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 2007; 25:4370-4378.
34. Schairer C, Hisada M, Chen BE, et al. Comparative mortality for 621 second cancers in 29356 testicular cancer survivors and 12420 matched first cancers. J Natl Cancer Inst 2007; 99:1248-1256.