Radiation Oncology/Testis/NSGCT

Non-Seminomatous Germ Cell Tumors (NSGCT) Subpage: NSGCT Randomized EvidencePrognostic factorsInternational 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 Treatment OverviewStage 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 RPLNDPositive tumor markersChemotherapy 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.Bulky Stage II-IIITreatment is BEP x 3 or EP x 4.Poor riskBEP x 4 leads to 50% cure rate. Investigational treatments may be offered. Adjuvant TherapyAUO 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 cycle5-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 SurveillanceFrequency 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 arms2007''' 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.