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ARTICLE
Year : 2011  |  Volume : 3  |  Issue : 4  |  Page : 17-20  

Saudi Oncology Society clinical management guidelines for testicular germ cell tumors


Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Date of Web Publication2-Apr-2011

Correspondence Address:
Mohammed Al Otaibi
King Faisal Specialist Hospital and Research Center, POBOX 3354, MBC 83, Riyadh - 11211
Saudi Arabia
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DOI: 10.4103/0974-7796.78551

PMID: 21673848

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   Abstract 

In this report, guidelines for the evaluation, medical and surgical management of transitional cell carcinoma of testicular germ cell tumors is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The recommendations are presented with supporting level of evidence.

Keywords: Testicular germ cell tumors, Saudi, guidelines, management


How to cite this article:
Al Otaibi M, El-naghi M, Balaraj K, Bazarbashi S, Rabbah D, Al Othman K, Al Saeed E, Al Ghamdi A, Aljubran A, Murshid E, Al Oraifi I, Al Kushi H. Saudi Oncology Society clinical management guidelines for testicular germ cell tumors. Urol Ann 2011;3, Suppl S1:17-20

How to cite this URL:
Al Otaibi M, El-naghi M, Balaraj K, Bazarbashi S, Rabbah D, Al Othman K, Al Saeed E, Al Ghamdi A, Aljubran A, Murshid E, Al Oraifi I, Al Kushi H. Saudi Oncology Society clinical management guidelines for testicular germ cell tumors. Urol Ann [serial online] 2011 [cited 2018 May 23];3, Suppl S1:17-20. Available from: http://www.urologyannals.com/text.asp?2011/3/4/17/78551


   Introduction Top


Testicular cancer is a rare disease. A total of 38 cases have been diagnosed in 2006, with an age standardized rate (ASR) of 0.5 cases per 100,000 representing 1% of all diagnosed cancer in Saudi Arabia (http://www.scr.org.sa).

Due to the rarity of the disease and the need for multidisciplinary approach in managing testis cancer the group recommended that 'All testicular cancer cases should be managed in tertiary care centers.'

A panel of experts in the management of testicular cancer was gathered under the umbrella of the Saudi Oncology Society. It included Urologists, Medical oncologists and Radiation oncologists. A subgroup was formed to work on testes cancer. The subgroup reviewed the literature, current international guidelines in testicular cancer management. The subgroup brought their recommendation to the panel where all references were discussed in several meetings and the guidelines were finalized.

We have used the following evidence level:

  • (EL1) High level: well-conducted phase III randomized trials or meta-analysis.
  • (EL2) intermediate level: good phase II trials or phase III with limitations.
  • (EL3) low level: Observational/retrospective studies or expert opinion.

   1. Staging Top


The American Joint Committee on Cancer (AJCC) TNM staging for testis cancer (7 th edition 2010) was used.


   2. Risk Stratification Top


The international Germ Cell Cancer Collaborative Group Risk Classification [1] should be used:

2.1. Good prognosis

2.1.1. For patients with seminoma:

2.1.1.1. Any primary site

2.1.1.2. No non-pulmonary visceral metastasis

2.1.1.3. Normal serum AFP, any serum beta-hCG or LDH

2.1.2. For patients with non-seminoma (NSGCT):

2.1.2.1. Testicular or retroperitoneal primary tumor

2.1.2.2. No non-pulmonary visceral metastasis

2.1.2.3. Serum AFP less than 1000 ng/mL, beta-hCG less than 5000 mIU/mL and LDH less than 1.5 times the upper limit of normal

2.2. Intermediate prognosis:

2.2.1. For patients with seminoma:

2.2.1.1. Any primary site

2.2.1.2. Non-pulmonary visceral metastasis

2.2.1.3. Normal serum AFP, any beta-hCG or LDH

2.2.2. For patients with NSGCT:

2.2.2.1. Testicular or retroperitoneal primary

2.2.2.2. No non-pulmonary visceral metastasis

2.2.2.3. Any of the following: serum AFP 1000 to 10,000 ng/mL; beta-hCG 5000 to 50,000 mIU/mL; LDH 1.5 to 10 times upper limit of normal

2.3. Poor prognosis:

2.3.1. For NSGCT only, any of the following:

2.3.1.1. Mediastinal primary site

2.3.1.2. Non-pulmonary visceral metastasis

2.3.1.3. Serum AFP >10,000 ng/mL; serum beta-hCG >50,000 mIU/mL; LDH more than 10 times upper limit of normal


   3. Treatment Top


Will depend on the histological subtype as follows:

3.1. Seminoma: All stages should undergo urgent inguinal orchiectomy. Trans-scrotal biopsy or orchiectomy for any intra-testicular lesion is absolutely contra-indicated. Further treatment will depend on the stage:

3.1.1. Stage I: One of the following adjuvant options:

3.1.1.1. Chemotherapy: single agent carboplatin: 1-2 doses at AUC 7. [2] (EL 1)

3.1.1.2. Radiotherapy: infradiaphragmatic para-aortic ± ipsilateral iliac nodes. [3],[4] (EL1)

3.1.1.3. Surveillance: this should be done only in compliant patients with primary tumors less than 4 cm and less than pT2. [5] (EL1)

3.1.2. Stage IIA and IIB:

3.1.2.1. Radiotherapy to infradiaphragmatic para-aortic and ipsilateral Iliac nodes. [6] (EL2)

3.1.2.2. For selected stage IIB, chemotherapy with four cycles of EP (Etoposide and cisplatin) or three cycles of BEP (bleomycin, etoposide and cisplatin). (EL2)

3.1.3. Stage IIC and III: treatment will depend on the risk classification:

3.1.3.1. Good risk: chemotherapy with four cycles of EP (for patients with compromised lung function), or three cycles of BEP. [7],[8] (EL1)

3.1.3.2. Intermediate risk: chemotherapy with four cycles of BEP. [9] (EL1)

3.1.4. Management of post-chemotherapy residual nodes/masses seen on CT scan: this depends on the size and the level of tumor marker. (HCG)

3.1.4.1. If size less than 3 cm and normal markers: surveillance

3.1.4.2. If more than 3 cm and normal markers: do PET scan: [10]

3.1.4.2.1. If negative: surveillance. (EL2)

3.1.4.2.2. If positive consider one of the following options:

3.1.4.2.2.1. Surgical resection

3.1.4.2.2.2. Biopsy and second-line chemotherapy if positive for residual disease (See item 3.2.5.3.2)

3.1.4.2.2.3. Radiotherapy

3.1.4.3. If the residual mass is enlarging or markers increasing: second-line chemotherapy (EL2) - See item 3.2.5.3.2

3.1.5. Management of patients failing first line chemotherapy: patients will receive second line chemotherapy; options are:

3.1.5.1. Four cycles of VeIP regimen (Vinblastine, Ifosfamide and cisplatin). [11] (EL2) or

3.1.5.2. Four cycles of TIP regimen (paclitaxel, Ifosfamide and cisplatin). [12] (EL 2)

3.1.6. Management of patients failing second line chemotherapy: patients will be treated with combination paclitaxel and Gemcitabine for those who did not receive paclitaxel before. [13]

3.2. Non-seminoma: all stages will undergo urgent inguinal orchiectomy. Trans-scrotal biopsy or orchiectomy for any intra-testicular lesion is absolutely contra-indicated. Further treatment will depend on the stage as follows:

3.2.1. Stage I:

3.2.1.1. Treatment will depend on the presence of any the following risk factors: [14]

3.2.1.1.1. Lymphovascular invasion

3.2.1.1.2. Presence of embryonal histology (50% or more) [15]

3.2.1.1.3. Absence of yolk sac histology

3.2.1.1.4. Tumor stage more than T1

3.2.1.2. Stage I with no risk factors; options are:

3.2.1.2.1. Surveillance: should be reserved in compliant patients. [16],[17] (EL2)

3.2.1.2.2. Two cycles of adjuvant chemotherapy with BEP regimen. [16],[17],[18] (EL1)

3.2.1.2.3. Open nerve sparing retroperitoneal lymph node dissection: to be done only in high-volume tertiary care centers [18] (EL2): further therapy will depend on the pathological result as follows:

3.2.1.2.3.1. pN0: surveillance

3.2.1.2.3.2. pN1: surveillance in compliant patients or two cycles of chemotherapy with BEP in non-compliant patients. (EL3)

3.2.1.2.3.3. pN2: three cycles of chemotherapy with BEP regimen. (EL3)

3.2.1.2.3.4. pN3: three cycles of chemotherapy with BEP regimen. (EL3)

3.2.1.3. Stage I with any risk factor of above; options are:

3.2.1.3.1. two cycles of adjuvant chemotherapy with BEP regimen [16]

3.2.1.3.2. Open nerve sparing retroperitoneal lymph node dissection (RPLND): to be done only in high-volume tertiary care centers [19] (EL2): further therapy will depend on the pathological stage as in item 3.2.1.2.3

3.2.1.4. Stage Is: patient should receive three cycles of systemic chemotherapy with the BEP regimen. (EL3)

3.2.2. Stage IIA and IIB: options of therapy will depend if markers (AFP and HCG) are normal or elevated:

3.2.2.1. Normal markers; options are:

3.2.2.1.1. Primary chemotherapy with three cycles of BEP [8]

3.2.2.1.2. Open nerve sparing RPLND, [20],[21] if the nodal metastasis is in the primary landing zone. Further therapy will depend on the pathological stage as in item 3.2.1.1.3

3.2.2.2. Elevated markers: systemic chemotherapy depending on the international risk classification group

3.2.2.2.1. Low risk: three cycles of BEP [7],[8]

3.2.2.2.2. Intermediate and high risk: four cycles of BEP9

3.2.3. Stage IIC and III: treatment will be with chemotherapy depending on the international risk classification:

3.2.3.1. Low risk: three cycles of BEP chemotherapy [7],[8]

3.2.3.2. Intermediate and high risk: four cycles of BEP chemotherapy [9]

3.2.4. Management of post chemotherapy:

3.2.4.1. No residual disease and normal markers: surveillance [22]

3.2.4.2. No residual disease and elevated markers (AFP and HCG): Second-line chemotherapy. See item 3.2.4.3.2

3.2.4.3. Residual disease by CT scan: this depend on the level of serum markers:

3.2.4.3.1. Normal markers: RPLND and resection of all residual disease if technically feasible: [23],[24] further therapy will depend on pathology result:

3.2.4.3.1.1. Mature teratoma, necrosis or fibrosis: no further therapy

3.2.4.3.1.2. Residual germ cell tumor: two cycles of chemotherapy [25] with EP, VIP or TIP (see below) (EL2)

3.2.4.3.2. Elevated markers: second line chemotherapy; options are:

3.2.4.3.2.1. Four cycles of VeIP regimen [11]

3.2.4.3.2.2. Four cycles of TIP regimen [12]

3.2.5. Management of patients failing second line chemotherapy: patients will be treated with paclitaxel and Gemcitabine if they did not receive paclitaxel before [13]

3.2.6. Management of patients failing all lines of chemotherapy: In the case of markers progression after salvage treatment and exhaustion of all possible chemotherapeutic options, resection of residual tumors (desperation surgery) should be considered if complete resection of all tumors seems technically feasible. [26]

 
   References Top

1.International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997;15:594-603.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Reiter WJ, Brodowicz T, Alavi S, Zielinski CC, Kozak W, Maier U, et al .Twelve-year experience with two courses of adjuvant single-agent carboplatin therapy for clinical stage I seminoma. J Clin Oncol 2001;19:101-4.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Fossa SD, Horwich A, Russell JM, Roberts JT, Cullen MH, Hodson NJ, et al. Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol 1999;17:1146.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, et al. Randomized trial of 30 Gy vs 20 Gy in the adjuvant treatment of stage I seminoma. A report on medical research council trial TE18. EORTC trial 30942. J Clin Oncol 2005;23:1200-8  Back to cited text no. 4
    
5.Warde P, Chung P, Sturgeon J, Panzarella T, Giuliani M, Tew-George B, et al. Should surveillance be considered the standard of care in stage I seminoma? (Abstract). J Clin Oncol 2005; 23:382s.  Back to cited text no. 5
    
6.Schmidberger H, Bamberg M, Meisner C, Classen J, Winkler C, Hartmann M, et al. Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: A prospective multicenter study. Int J Radiat Oncol Biol Phys 1997;39:321-6  Back to cited text no. 6
    
7.Einhorn LH, Williams SD, Loehrer PJ, Birch R, Drasga R, Omura G, et al. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: A Southeastern Cancer Study Group protocol. J Clin Oncol 1989;7:387-91.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Toner GC, Stockler MR, Boyer MJ, Jones M, Thomson DB, Harvey VJ. Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: A randomised trial. Australian and New Zealand Germ Cell Trial Group. Lancet 2001;357:739-45.  Back to cited text no. 8
    
9.Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987;316:1435-40.  Back to cited text no. 9
    
10.De Santis M, Bokemeyer C, Becherer A, Stoiber F, Oechsle K, Kletter K, et al. Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma. J Clin Oncol 2001;19:3740-4.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Loehrer PJ Sr, Lauer R, Roth BJ, Williams SD, Kalasinski LA, Einhorn LH. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 1988;109:540-6.  Back to cited text no. 11
[PUBMED]    
12.Mead GM, Cullen MH, Huddart R, Harper P, Rustin GJ, Cook PA, et al. A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: A medical research council trial. Br J Cancer 2005;93:178-84.  Back to cited text no. 12
    
13.Hinton S, Catalano P, Einhorn LH, Loehrer PJ Sr, Kuzel T, Vaughn D, et al. Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): A trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2002;20:1859-63.  Back to cited text no. 13
[PUBMED]  [FULLTEXT]  
14.Klepp O, Dahl O, Flodgren P, Stierner U, Olsson AM, Oldbring J, et al. Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer. Eur J Cancer 1997;33:1038-44.  Back to cited text no. 14
[PUBMED]  [FULLTEXT]  
15.Heidenreich A, Sesterhenn IA, Mostofi FK, Moul JW. Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Cancer 1998;83:1002-11.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.Tandstad T, Dahl O, Cohn-Cedermark G, Cavallin-Stahl E, Stierner U, Solberg A, et al. Risk-adapted treatment in clinical stage I nonseminomatous germ cell testicular cancer: The SWENOTECA management program. J Clin Oncol 2009;27:2122-8.  Back to cited text no. 16
[PUBMED]  [FULLTEXT]  
17.Sogani PC, Perrotti M, Herr HW, Fair WR, Thaler HT, Bosl G. Clinical stage I testis cancer: long-term outcome of patients on surveillance. J Urol 1998;159:855-8.  Back to cited text no. 17
[PUBMED]  [FULLTEXT]  
18.Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, et al. 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. J Clin Oncol 2008;26:2966-72.   Back to cited text no. 18
[PUBMED]  [FULLTEXT]  
19.Sweeney CJ, Hermans BP, Heilman DK, Foster RS, Donohue JP, Einhorn LH. Results and outcome of retroperitoneal lymph node dissection for clinical stage I embryonal carcinoma--predominant testis cancer. J Clin Oncol 2000;18:358-62.  Back to cited text no. 19
[PUBMED]  [FULLTEXT]  
20.Williams SD, Stablein DM, Einhorn LH, Muggia FM, Weiss RB, Donohue JP, et al. Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 1987;317:1433-8.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.Donohue JP, Thornhill JA, Foster RS, Bihrle R, Rowland RG, Einhorn LH. The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: The Indiana University experience (1965 to 1989). J Urol 1995;153:85-9.  Back to cited text no. 21
[PUBMED]    
22.Ehrlich Y, Brames MJ, Beck SD, Foster RS, Einhorn LH. 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;28:531-6.  Back to cited text no. 22
[PUBMED]  [FULLTEXT]  
23.Kollmannsberger C, Daneshmand S, So A, Chi KN, Murray N, Moore C, et al. Management of disseminated nonseminomatous germ cell tumors with risk-based chemotherapy followed by response-guided postchemotherapy surgery. J Clin Oncol 2010;28:537-42.  Back to cited text no. 23
[PUBMED]  [FULLTEXT]  
24.Carver BS, Shayegan B, Serio A, Motzer RJ, Bosl GJ, Sheinfeld J. Long-term clinical outcome after postchemotherapy retroperitoneal lymph node dissection in men with residual teratoma. J Clin Oncol 2007;25:1033-7.  Back to cited text no. 24
[PUBMED]  [FULLTEXT]  
25.Fizazi K, Tjulandin S, Salvioni R, Germa-Lluch JR, Bouzy J, Ragan D, et al . Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: Prognostic factors and role of postsurgery chemotherapy--results from an international study group. J Clin Oncol 2001;19:2647-57.  Back to cited text no. 25
    
26.Beck SD, Foster RS, Bihrle R, Einhorn LH, Donohue JP. Outcome analysis for patients with elevated serum tumor markers at postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol 2005;23:6149-56.  Back to cited text no. 26
[PUBMED]  [FULLTEXT]  




 

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