title: A refined risk stratification scheme for clinical stage 1 NSGCT based on evaluation of both embryonal predominance and lymphovascular invasion.
abstract: BACKGROUND
  Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy.
  
  
  METHODS
  We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method.
  
  
  RESULTS
  Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median time-to-relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/8.5 months, 41%/6.8 months and 78%/3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108).
  
  
  CONCLUSIONS
  NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT.
authors.affiliation: Harvard Medical School, Boston Department of Medical Oncology-Genitourinary Division, Dana-Farber Cancer Institute, Boston.
authors.forename: C A
authors.initials: CA
authors.lastname: Lago-Hernandez
authors.affiliation: Albert Einstein College of Medicine, New York Department of Medical Oncology-Genitourinary Division, Dana-Farber Cancer Institute, Boston.
authors.forename: H
authors.initials: H
authors.lastname: Feldman
authors.affiliation: Department of Medical Oncology-Genitourinary Division, Dana-Farber Cancer Institute, Boston.
authors.forename: E
authors.initials: E
authors.lastname: O'Donnell
authors.affiliation: Harvard Medical School, Boston Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: B A
authors.initials: BA
authors.lastname: Mahal
authors.affiliation: University of Puerto Rico Medical School, San Juan PR.
authors.forename: V
authors.initials: V
authors.lastname: Perez
authors.affiliation: Departments of Imaging, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Howard
authors.affiliation: Departments of Imaging, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rosenthal
authors.affiliation: Biostatistics/Computational Biology, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Cheng
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: P L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: C
authors.initials: C
authors.lastname: Beard
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston.
authors.forename: A V
authors.initials: AV
authors.lastname: D'Amico
authors.affiliation: Department of Medical Oncology-Genitourinary Division, Dana-Farber Cancer Institute, Boston christopher_sweeney@dfci.harvard.edu.
authors.forename: C J
authors.initials: CJ
authors.lastname: Sweeney
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018236:Carcinoma, Embryonal / Q000401:mortality / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000401:mortality / Q000473:pathology*; D011159:Population Surveillance; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D018239:Seminoma / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000401:mortality / Q000473:pathology*; D055815:Young Adult
keywords: active surveillance; clinical stage 1; embryonal predominance; lymphovascular invasion; nonseminoma germ-cell tumor; relapse