Radiation Oncology/Testis/NSGCT

Non-Seminomatous Germ Cell Tumors (NSGCT)

Prognostic factors

International Germ Cell Cancer Collaborative Group:

PMID 9053482, 1997 — "International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers." J Clin Oncol 1997;15(2):594-603.
Non-seminomatous tumors:
- Good risk: Testicular or retroperitoneal primary tumor AND No nonpulmonary visceral metastasis AND good markers (see below)
  Good markers (all of the following):
  
  AFP <1,000 ng/mL
  
  hCG <5,000 mIU/mL
  
  LDH <1.5 x ULN
- Intermediate risk: Same as good risk but with Intermediate markers
  Intermediate markers (any of the following):
  
  AFP 1,000-10,000 ng/mL
  
  hCG 5,000-50,000 mIU/mL
  
  LDH 1.5-10 x ULN
- Poor risk: Mediastinal primary tumor OR Nonpulmonary visceral metastasis OR Poor markers
  Poor markers (any of the following):
  
  AFP >10,000 ng/mL
  
  hCG >50,000 mIU/mL
  
  LDH >10 x ULN

Stage I, Good and intermediate risk:
- Treatment is orchiectomy alone.
  - 30% chance of relapse after orchiectomy if tumor markers are normal at time of treatment.
- Adjuvant treatment:
  - Observation vs retroperitoneal lymph node dissection - ultimately 99% will be cured.
  - Observation:
    - Assessment of tumor markers q1month for first year, q2m for 2nd year, q6m for years 3-5, then yearly starting with the sixth year. CT scan of the abdomen q2m (year 1), q4m (year 2), q6m (year 3-5).
  - RPLND:
    - 30% chance of positive nodes on dissection despite node-negative CT. Relapse rate is 10% after lymph node dissection, primarily to lungs.
    - RPLND leads to 96% PFS for Stages I-IIA with normal markers after surgery. Not indicated for Stage IIB or higher or persistent tumor markers.
  - BEP (bleomycin, etoposide, cisplatin) x1 cycle
    - German randomized trial showed this approach superior to RPLND
Positive tumor markers
- Chemotherapy indicated for Stage IIB or higher or positive tumor markers after surgery.

Stage II (positive node discovered only after lymph node dissection)
Relapse rate 30-50%. Treatment is BEP x 2 cycles.

Poor risk
BEP x 4 leads to 50% cure rate. Investigational treatments may be offered.

AUO AH 01/94 (Germany)(1996-2005) -- RPLND vs. BEP 1 cycle
- Randomized. 382 patients, clinical Stage I NSGCT. Arm 1) retroperitoneal lymph node dissection vs. Arm 2) bleomycin, etoposide, cisplatin (BEP) x1 cycle
- 5-years; 2008 PMID 18458040 -- "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." (Albers P, J Clin Oncol. 2008 Jun 20;26(18):2966-72. Epub 2008 May 5.). Median F/U 4.7 years
  - Outcome: 2-year RFS surgery 92% vs. BEP 99% (HR 7.9, SS)
  - Conclusion: One course of BEP is superior over RPLND in clinical Stage I disease

Frequency of CT scans:

MRC Trial TE08 (1998-2003) -- 2 CT scans vs 5 CT scans
- Randomized. 414 patients, clinical Stage I NSGCT. Treated with orchiectomy. 10% high risk (LVI). Normal serum markers. Arm 1) 2 CT scans (3 and 12 months) vs. Arm 2) 5 CT scans (3, 6, 9, 12, and 24 months). CT was chest/abdomen; all other investigations (CXR, serum markers) were same between arms
- 2007 PMID 17416851 — "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." (Rustin GJ et al. J Clin Oncol. 2007 Apr 10; 25(11):1310-1315.) Median F/U 3.3 years
  - Outcome: 2-year RFS 2-scan 79% vs. 5-scan 84% (NS). For pts with vascular invasion, relapse 63% to 67%. No pts relapsed with poor prognosis disease; intermediate prognosis relapse in 2 pts (5.6% of relapses) in 2 scan group and 1 pt (3%) in 5 scan group.
  - First indication of relapse: markers 39%, abd CT 39%. 9 relapses were picked up by the 12 month CT scan.
  - Conclusion: CT scans at 3 months and 12 months after orchiectomy reasonable options in low-risk patients. 12 month CT scan is necessary. Chest CT may be unnecessary. LDH is not useful in follow-up.