Management of stage II nonseminomatous germ cell tumors
- Timothy D Gilligan, MD
Timothy D Gilligan, MD
- Associate Professor of Medicine
- Cleveland Clinic Lerner College of Medicine
- Vice-Chair for Education
- Cleveland Clinic Taussig Cancer Institute
- Director of Coaching, Center for Excellence in Healthcare Communication
- Cleveland Clinic
- Philip W Kantoff, MD
Philip W Kantoff, MD
- Section Editor — Testicular Cancer
- Chairman of Medicine
- Memorial Sloan Kettering Cancer Center
Testicular cancers, 95 percent of which are germ cell tumors (GCTs), are one of the most curable solid tumors. Testicular GCTs are more sensitive to systemic chemotherapy than most adult solid tumors. Chemotherapy is routinely administered with curative intent for men with metastatic seminomas or nonseminomatous GCTs (NSGCTs; ie, stage III disease (table 1A-B)) and for those with persistently elevated serum tumor markers following orchiectomy (stage Is).
The management of stage II NSGCTs requires an understanding of the appropriate roles of chemotherapy and retroperitoneal lymph node dissection (RPLND). In addition to chemotherapy, a curative approach to testicular cancer often requires surgery, in part because primary and metastatic tumors may contain teratoma, which is less prone to dissemination but more resistant to chemotherapy than other GCT histologies. (See "Serum tumor markers in testicular germ cell tumors".)
The management of stage II NSGCTs following orchiectomy will be reviewed here. An overview of the management of testicular cancer and the management of other stages of testicular cancer are discussed separately. (See "Overview of the treatment of testicular germ cell tumors" and "Management of stage I nonseminomatous germ cell tumors" and "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
Stage II disease refers to cancers that have spread to the regional (ie, retroperitoneal) lymph nodes (table 2). Stage II disease can be defined based on either imaging alone (clinical stage II) or on a histopathological analysis showing germ cell tumor (GCT) in lymph nodes resected during a retroperitoneal lymph node dissection (RPLND) (pathologic stage II).
The length of short axis in the transverse plane is used to determine whether or not a lymph node is enlarged on cross-sectional imaging. (The length of lymph nodes in the craniocaudal direction, as can be measured if coronal or sagittal plane images are constructed, is of no importance to staging; all measurement cutoffs in this section refer to measurements in the transverse plane).
- Stephenson AJ, Bosl GJ, Motzer RJ, et al. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol 2005; 23:2781.
- Leibovitch L, Foster RS, Kopecky KK, Donohue JP. Improved accuracy of computerized tomography based clinical staging in low stage nonseminomatous germ cell cancer using size criteria of retroperitoneal lymph nodes. J Urol 1995; 154:1759.
- Donohue JP, Thornhill JA, Foster RS, et al. The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 1995; 153:85.
- Weissbach L, Bussar-Maatz R, Flechtner H, et al. RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment. Eur Urol 2000; 37:582.
- Stephenson AJ, Bosl GJ, Motzer RJ, et al. Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIA and IIB nonseminomatous germ cell testicular cancer. J Clin Oncol 2007; 25:5597.
- Williams SD, Stablein DM, Einhorn LH, et al. Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 1987; 317:1433.
- Ehrlich Y, Brames MJ, Beck SD, et al. Long-term follow-up of Cisplatin combination chemotherapy in patients with disseminated nonseminomatous germ cell tumors: is a postchemotherapy retroperitoneal lymph node dissection needed after complete remission? J Clin Oncol 2010; 28:531.
- Donohue JP, Thornhill JA, Foster RS, et al. Clinical stage B non-seminomatous germ cell testis cancer: the Indiana University experience (1965-1989) using routine primary retroperitoneal lymph node dissection. Eur J Cancer 1995; 31A:1599.
- Chung PW, Bedard P. Stage II seminomas and nonseminomas. Hematol Oncol Clin North Am 2011; 25:529.
- Rabbani F, Sheinfeld J, Farivar-Mohseni H, et al. Low-volume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse. J Clin Oncol 2001; 19:2020.
- Ravi P, Gray KP, O'Donnell EK, Sweeney CJ. A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic non-seminomatous germ cell tumor. Ann Oncol 2014; 25:331.
- Beck SD, Cheng L, Bihrle R, et al. Does the presence of extranodal extension in pathological stage B1 nonseminomatous germ cell tumor necessitate adjuvant chemotherapy? J Urol 2007; 177:944.
- Hermans BP, Sweeney CJ, Foster RS, et al. Risk of systemic metastases in clinical stage I nonseminoma germ cell testis tumor managed by retroperitoneal lymph node dissection. J Urol 2000; 163:1721.
- Hartlapp JH, Weissbach L, Bussar-Maatz R. Adjuvant chemotherapy in nonseminomatous testicular tumour stage II. Int J Androl 1987; 10:277.
- Pizzocaro G, Piva L, Salvioni R, et al. Adjuvant chemotherapy in resected stage-II nonseminomatous germ cell tumors of testis. In which cases is it necessary? Eur Urol 1984; 10:151.
- Richie JP, Kantoff PW. Is adjuvant chemotherapy necessary for patients with stage B1 testicular cancer? J Clin Oncol 1991; 9:1393.
- Tait D, Peckham MJ, Hendry WF, Goldstraw P. Post-chemotherapy surgery in advanced non-seminomatous germ-cell testicular tumours: the significance of histology with particular reference to differentiated (mature) teratoma. Br J Cancer 1984; 50:601.
- Donohue JP, Thornhill JA, Foster RS, et al. Retroperitoneal lymphadenectomy for clinical stage A testis cancer (1965 to 1989): modifications of technique and impact on ejaculation. J Urol 1993; 149:237.
- Beck SD, Foster RS, Bihrle R, et al. Impact of the number of positive lymph nodes on disease-free survival in patients with pathological stage B1 nonseminomatous germ cell tumor. J Urol 2005; 174:143.
- Motzer RJ, et al. National Comprehensive Cancer Network Practice Guidelines in Oncology: Testicular Cancer, National Comprehensive Cancer Network, Rockledge, PA 2001. Vol Version 1.2002.
- Behnia M, Foster R, Einhorn LH, et al. Adjuvant bleomycin, etoposide and cisplatin in pathological stage II non-seminomatous testicular cancer. the Indiana University experience. Eur J Cancer 2000; 36:472.
- Kondagunta GV, Sheinfeld J, Mazumdar M, et al. Relapse-free and overall survival in patients with pathologic stage II nonseminomatous germ cell cancer treated with etoposide and cisplatin adjuvant chemotherapy. J Clin Oncol 2004; 22:464.
- Motzer RJ, Sheinfeld J, Mazumdar M, et al. Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors. J Clin Oncol 1995; 13:2700.
- CLINICAL STAGE II NSGCT
- Normal tumor markers
- - Clinical stage IIA
- - Clinical stage IIB to IIC
- Elevated tumor markers
- Treatment of residual masses
- PATHOLOGIC STAGE II NSGCT
- Pathologic stage IIA disease
- Pathologic stage IIB/C disease
- SPECIAL CONSIDERATIONS
- SUMMARY AND RECOMMENDATIONS