Update on testicular germ cell tumors

Current Opinion in Oncology

Volumn 21, Issue 3, 2009, Pages 254-259

  Mannuel, Heather D ^a,c,d   Hussain, Arif ^b,c  

^a Department of Medicine ^*  (United States)

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

^c BALTIMORE VA MEDICAL CENTER   (United States)

^d UNIVERSITY OF MARYLAND   (United States)

Author keywords

Chemotherapy; Genetic studies; Germ cell tumor; Imaging; Late relapse; Nonseminomatous germ cell tumor; Retroperitoneal lymph node dissection; Seminoma; Surgery; Surveillance

Indexed keywords

ANTINEOPLASTIC AGENT; BLEOMYCIN; BLEOMYCIN HYDROLASE; CARBOPLATIN; CISPLATIN; CYCLOPHOSPHAMIDE; DOXORUBICIN; ETOPOSIDE; FLUORODEOXYGLUCOSE F 18; PLATINUM; VINBLASTINE;

CANCER COMBINATION CHEMOTHERAPY; CANCER INCIDENCE; CANCER STAGING; COMPUTER ASSISTED TOMOGRAPHY; DIARRHEA; DISEASE SEVERITY; DRUG MEGADOSE; GENE EXPRESSION; GENETIC POLYMORPHISM; GENOMICS; GENOTYPE; GERM CELL TUMOR; HETEROZYGOSITY LOSS; HUMAN; IMMUNOHISTOCHEMISTRY; LEUKOPENIA; LYMPH NODE DISSECTION; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; MORTALITY; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; POLYMERASE CHAIN REACTION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; SEMINOMA; SINGLE NUCLEOTIDE POLYMORPHISM; STOMATITIS; TESTIS TUMOR; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE; WILD TYPE; DRUG RESISTANCE; GENETICS; MALE; NEOPLASM; RECURRENT DISEASE; RISK FACTOR;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DRUG RESISTANCE, NEOPLASM; HUMANS; MALE; NEOPLASMS, GERM CELL AND EMBRYONAL; RECURRENCE; RISK FACTORS; TESTICULAR NEOPLASMS;

EID: 67650376191     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/CCO.0b013e32832a2ced     Document Type: Review

References (22)

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4. Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007; 97:1701-1706.
5. Akre O, Pettersson A, Ricchiardi L. Risk of contralateral testicular cancer among men with unilaterally undescended testis: a meta analysis. Int J Cancer 2009; 124:687-689. 6 Pettersson A, Richiardi L, Cnattingius S, et al. Gestational hypertension, preeclampsia, and risk of testicular cancer. Cancer Res 2008; 68:8832-8836. This large study evaluates a possible relationship between prenatal exposure to maternal hormonal fluctuations with preeclampsia and future development of TGCTs in offsprings.
6. Cook MB, Graubard BI, Rubertone MV, et al. Perinatal factors and the risk of testicular germ cell tumors. Int J Cancer 2008; 122:2600-2606.
7. Holl K, Surcel HM, Koskela P, et al. Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study. APMIS 2008; 116:816-822.
8. Mai PL, Friedlander M, Tucker K, et al. The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urol Oncol 2009. [Epub ahead of print]
9. Sakuma Y, Matsukuma S, Yoshihara M, et al. Mutations of c-kit gene in bilateral testicular germ cell tumours in Japan. Cancer Lett 2008; 259:119-126. In this study, 12 bilateral TGCTs and 39 unilateral TGCTs in Japanese men were evaluated for c-kit mutations. c-kit mutations were found in 18% of unilateral tumors but not in bilateral tumors; as prior studies have noted these mutations in up to 40% of European patients with bilateral tumors, it is postulated that different mutational activity may be present in Japanese versus European men with TGCT.
10. Velasco A, Corvalan A, Wistuba II, et al. Mismatch repair and expression in testicular cancer predicts recurrence and survival. Int J Cancer 2008; 122:1774-1777. One hundred and sixty-two cases of TGCTs were evaluated for degree of MMR immunoreactivity and genetic instability in the form of LOH and MSI. Degree of MMR expression was associated with a shorter time to recurrence and relapse, increased chemotherapy resistance, and death. Increased rates of relapse and cancer-specific death were associated with tumors exhibiting a high degree of MSI, but this association was not seen with LOH.
11. de Haas EC, Zwart N, Meijer C, et al. Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer. J Clin Oncol 2008; 26:1817-1823. This large study evaluated the gene for BLMH, specifically the SNP A1450G, to determine whether it was associated with survival differences in men treated with bleomycin-containing regimens for nonseminoma TGCTs. The homozygous variant G/G was associated with decreased cancer-related survival and a higher prevalence of early disease relapse compared with the heterozygous variant A/G and the wild-type gene A/A.
12. Oechsle K, Hartmann M, Brenner W, et al. [18F] Fluorodeoxyglucose positron emission tomography in nonseminomatous germ cell tumors after chemotherapy: the German multicenter positron emission tomography study group. J Clin Oncol 2008; 26:5930-5935. The study group performed FDG-PET scans on 121 patients with stage IIc or stage III nonseminoma TGCTs with residual masses after cisplatin-based chemotherapy, with the primary aim to evaluate whether PET was able to distinguish between viable tumor, teratoma, and fibrosis with an accuracy of 80%. The primary endpoint was not reached, with similar accuracies, positive predictive values, and negative predictive values in the range of 50-60% for PET, CT, and serum tumor markers.
13. Dash A, Carver BS, Stasi J, et al. The indication for postchemotherapy lymph node dissection in clinical stage IS nonseminomatous germ cell tumor. Cancer 2008; 112:800-805. Twenty-four patients treated at a single institution for cIS nonseminoma GST were evaluated for clinical outcome, pattern of relapse, and pathologic findings. Seven patients underwent primary RPLND and seven others underwent RPLND after chemotherapy. There was a 43% incidence of viable tumor or teratoma in the postchemotherapy group. This study suggests that RPLND remains beneficial in optimizing outcomes in patients with cIS disease.
14. Ong TA, Winkler MH, Savage PM, et al. Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumor markers: indications, histopathology and outcome. BJU Int 2008; 102:198-202. The authors evaluated 358 patients who underwent RPLND over a 14-year period. At the time of surgery, tumor markers remained elevated in 48 patients. The overall incidence of active GCT and differentiated teratoma in resected specimens was 58 and 25%, respectively, and at median follow-up the overall survival rate was 69%. In this population, RPLND may prolong survival and obviate the need for potentially toxic chemotherapy.
15. Steiner H, Peschel R, Bartsch G. Retroperitoneal lymph node dissection after chemotherapy for germ cell tumours: is a full bilateral template always necessary? BJU Int 2008; 102:310-314. The authors evaluated 102 men with stage II nonseminoma GCT, of whom 78 had a unilateral RPLND and 24 underwent modified template RPLND. The overall antegrade ejaculation rate for the combined groups was 94%, and only three recurrences were documented at median follow-up. In this group of men with lowvolume ipsilateral stage II disease, modified template RPLND may offer both oncological efficacy and fertility preservation.
16. Cresswell J, Scheitlin W, Gozen A, et al. Laparoscopic retroperitoneal lymph node dissection combined with adjuvant chemotherapy for pathological stage II disease in nonseminomatous germ cell tumors: a 15-year experience. BJU Int 2008; 102:844-848.
17. Garcia-del-Muro X, Maroto P, Guma J, et al. Chemotherapy as an alternative to radiotherapy in the treatment of stage IIA and IIB testicular seminoma: a Spanish Germ Cell Cancer Group Study. J Clin Oncol 2008; 26:5416-5421. This is a prospective observational study of 72 patients with stage IIA or IIB seminoma who underwent either three cycles of BEP or four cycles of etoposide and cisplatin postorchiectomy. Eighty-three percentage of patients achieved a complete response, and the overall 5-year survival rate was 95%. Toxicities were transient and consisted mainly of grade III neutropenia. Platinum-based therapy appears to be an effective and well tolerated alternative to radiation in this patient population.
18. Albers P, Siener R, Krege S, et al. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I nonseminomatous testicular germ cell tumors: AUO Trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol 2008; 26:2966-2972. This is the largest known phase III clinical trial investigating RPLND versus adjuvant chemotherapy in men with clinical stage I nonseminoma GCT. Three hundred and eighty-two patients were randomized to receive either RPLND or one cycle of adjuvant BEP. At median follow-up of 4.7 years, 2-year survival rate was 7.59% in favor of the chemotherapy arm (P=0.0033). Given its acceptable toxicity profile and favorable reduction in disease recurrence compared with RPLND, a single cycle of adjuvant BEP may represent a viable alternative for this patient subset.
19. Culine S, Kramar A, Theodore C, et al. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/ doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol 2008; 26:421-427.
20. Agarwal R, Dvorak CC, Stockerl-Goldstein KE, et al. High-dose chemotherapy followed by stem cell rescue for high-risk germ cell tumors: the Stanford experience. Bone Marrow Transplant 2008. [Epub ahead of print]
21. Oldenburg J, Martin JM, Fossa SD. Late relapses of germ cell malignancies: incidence, management, and prognosis. J Clin Oncol 2006; 24:5503-5511.
22. Sharp DS, Carver BS, Eggener SE, et al. Clinical outcome and predictors of survival in late relapse of germ cell tumor. J Clin Oncol 2008; 26:5524-5529. The authors reviewed 75 patients who were managed at a single institution for late relapse of TGCT. Although the median time to late relapse was 6.9 years, some patients relapsed decades after initial presentation. Seventy-five percent of patients experienced relapse in the retroperitoneum, including 93% who were managed without initial RPLND. Patients who underwent complete surgical resection at the time of late relapse had a 5-year CSS of 79%, compared with 36% for patients without complete resection. This study highlights the importance of achieving meticulous control of the retroperitoneum to minimize the risks of late relapse.