title: Late relapses (>2 years) in patients with stage I testicular germ cell tumors: predictive factors and survival.
abstract: OBJECTIVE
  Late relapses (>2 years) after completion of chemotherapy are rare and often platinum-resistant. There are limited data concerning late relapses in chemotherapy-naïve patients with stage I germ cell tumors. This retrospective analysis was performed to compare the outcome between patients with stage I germ cell tumors, who had late (≥2 years) and early (≥3 months and <2 years) relapse after orchiectomy.
  
  
  METHODS
  We analyzed data of 1,069 chemotherapy-naïve patients with advanced germ cell tumors of testis treated in our department from 1986 to 2008. All patients had cisplatin- and etoposide-based chemotherapy. We identified 169 (15.8%) patients with prior stage I disease, who had not received adjuvant treatment: 140 and 29 patients had early and late relapse, respectively. Among patients with late relapse, pure seminoma was revealed in 14 patients, and nonseminoma in 15 patients. Median follow-up time for 169 patients was 35 (range, 2-218) months.
  
  
  RESULTS
  Patients with late relapse were older, 35 years (23-57) and had more frequent pure seminoma in primary tumor, 14/29 (48.3%), than patients with early relapse, 30 years (16-63) (P = 0.0008) and 46/140 (32,8%, P = 0.08), respectively. At the time of disease progression, both groups were very similar according to well-known prognostic factors including IGCCCG classification. The only difference was larger size of retroperitoneal lymph nodes in late (9 cm) than in early relapse (4 cm, P < 0.0001). The outcome in patients with late relapse was significantly worse than in patients with early relapse: complete response rate after induction chemotherapy was 20.7% (6/29) vs. 42.1% (59/140) (P = 0.01), 3-year progression-free survival 66% vs. 84% (P = 0.02, HR = 2.4, 95% CI 1.2-8.8) and 3-year overall survival, 72% vs. 88% (P = 0.04, HR = 2.4, 95% CI 1.05-10.25), respectively. In patients with pure seminoma, this difference in overall survival was even more significant: 65% vs. 91% (P = 0.04, HR = 3.8, 95% CI 1.06-32.4).
  
  
  CONCLUSIONS
  Late relapses following stage I germ cell tumors were associated with seminoma, older age, and worse outcome after induction chemotherapy.
authors.affiliation: Department of Clinical Pharmacology and Chemotherapy, N. N. Blokhin Russian Cancer Research Center, Moscow, Russia. fedianinmu@mail.ru
authors.forename: Mikhail
authors.initials: M
authors.lastname: Fedyanin
authors.forename: Alexey
authors.initials: A
authors.lastname: Tryakin
authors.forename: Dheepak
authors.initials: D
authors.lastname: Kanagavel
authors.forename: Anatoly
authors.initials: A
authors.lastname: Bulanov
authors.forename: Alena
authors.initials: A
authors.lastname: Burova
authors.forename: Konstantin
authors.initials: K
authors.lastname: Figurin
authors.forename: Igor
authors.initials: I
authors.lastname: Fainshtein
authors.forename: Uriy
authors.initials: U
authors.lastname: Sergeev
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zakharova
authors.forename: August
authors.initials: A
authors.lastname: Garin
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009919:Orchiectomy / Q000401:mortality*; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D055815:Young Adult
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide