|Year : 2014 | Volume
| Issue : 4 | Page : 290-294
Saudi oncology society and Saudi urology association combined clinical management guidelines for testicular germ cell tumors
Mohammed Alotaibi1, Shouki Bazarbashi2, Sultan Alkhateeb3, Ashraf Abusamra4, Danny Rabah5, Mubarak Almansour6, Esam Murshid7, Abdullah Alsharm8, Imran Ahmad9, Khalid Alghamdi10, Ahmad Saadeddin11, Abdullah Alghamdi12
1 Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 Oncology center Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
3 Department of Surgery, Division of Urology, Riyadh, Saudi Arabia
4 Section of Urology, Department of Surgery, King Khaled Hospital, Jeddah, Saudi Arabia
5 Department of Surgery, Division of Urology, College of Medicine, King Khalid University Hospital; Princess Al-Johora Al-Ibrahim Centre for Cancer Research (Uro-Oncology Research Chair), King Saud University, Riyadh, Saudi Arabia
6 Oncology department, Princess Noura Oncology Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia
7 Department of Oncology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
8 Department of Oncology, King Fahad Medical City, Riyadh, Saudi Arabia
9 Department of Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
10 Division of Urology, Security Forces Hospital, Riyadh, Saudi Arabia
11 Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
12 Department of Urology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
|Date of Submission||15-Apr-2014|
|Date of Acceptance||15-Apr-2014|
|Date of Web Publication||18-Sep-2014|
Department of Surgery, Division of Urology, College of Medicine, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia Princess Al Johora Al Ibrahim Centre for Cancer Research (Uro Oncology Research Chair), King Saud University, Riyadh
| Abstract|| |
In this report, updated guidelines for the evaluation, medical, and surgical management of germ cell tumor of testes are resented. They are categorized according the stage of the disease using the tumor-node-metastasis staging system 7 th edition. The recommendations are presented with supporting level of evidence.
Keywords: Guidelines, management, Saudi, testicular germ cell tumors
|How to cite this article:|
Alotaibi M, Bazarbashi S, Alkhateeb S, Abusamra A, Rabah D, Almansour M, Murshid E, Alsharm A, Ahmad I, Alghamdi K, Saadeddin A, Alghamdi A. Saudi oncology society and Saudi urology association combined clinical management guidelines for testicular germ cell tumors. Urol Ann 2014;6:290-4
|How to cite this URL:|
Alotaibi M, Bazarbashi S, Alkhateeb S, Abusamra A, Rabah D, Almansour M, Murshid E, Alsharm A, Ahmad I, Alghamdi K, Saadeddin A, Alghamdi A. Saudi oncology society and Saudi urology association combined clinical management guidelines for testicular germ cell tumors. Urol Ann [serial online] 2014 [cited 2020 Jan 19];6:290-4. Available from: http://www.urologyannals.com/text.asp?2014/6/4/290/140978
| Manuscript|| |
Testicular cancer is a rare disease. A total of 78 cases have been diagnosed in 2010, with an age standardized rate of 0.8 cases/100,000 representing 1.7% of all diagnosed cancer in Saudi males (www.scr.org.sa). Owing 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.
1. Staging: The American Joint Committee on Cancer tumor-node-metastasis staging for testis cancer (7 th edition 2010) was used.
2. Staging evaluation of testicular tumors.
2.1. Ultrasound of the scrotum is recommended to diagnose the tumor
2.2. Serum tumor markers includes alpha fetoprotein [AFP], beta human chorionic gonadotropin [beta-hCG], and Lactate Dehydrogenase (LD) should prior to orchiectomy
2.3. Computed tomography (CT) chest, abdomen and pelvis should performed for confirmed testicular cancer.
3. Risk stratification: The International Germ Cell Cancer Collaborative Group Risk Classification  should be used:
3.1. Good prognosis.
3.1.1. For patients with seminoma:
188.8.131.52. Any primary site
184.108.40.206. No nonpulmonary visceral metastasis
220.127.116.11. Normal serum AFP, any serum beta-hCG or lactate dehydrogenase (LDH)
3.1.2. For patients with nonseminoma germ cell tumor (NSGCT):
18.104.22.168. Testicular or retroperitoneal primary tumor.
22.214.171.124. No nonpulmonary visceral metastasis.
126.96.36.199. Serum AFP <1000 ng/mL, beta-hCG < 5000 mIU/mL, and LDH < 1.5 times the upper limit of normal.
3.2. Intermediate prognosis:
3.2.1. For patients with seminoma:
188.8.131.52. Any primary site
184.108.40.206. Nonpulmonary visceral metastasis
220.127.116.11. Normal serum AFP, any beta-hCG or LDH
3.2.2. For patients with NSGCT:
18.104.22.168. Testicular or retroperitoneal primary.
22.214.171.124. No nonpulmonary visceral metastasis.
126.96.36.199. Any of the following: serum AFP 1,000-10,000 ng/mL; beta-hCG 5000-50,000 mIU/mL; LDH 1.5-10 times the upper limit of normal.
3.3. Poor prognosis:
3.3.1. For NSGCT only, any of the following:
188.8.131.52. Mediastinal primary site.
184.108.40.206. Nonpulmonary visceral metastasis.
220.127.116.11. Serum AFP > 10,000 ng/mL; serum beta-hCG > 50,000 mIU/mL; LDH more than 10 times the upper limit of normal
4. Treatment: All patients who will undergo treatment with chemotherapy, RPLND or Radiotherapy should offered sperm banking. The treatment will depend on the histological subtype as follow:
4.1. 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:
4.1.1. Stage I: Patient could offered one of the following options:
18.104.22.168. Chemotherapy: Single agent carboplatin: 1-2 doses at area under the curve 7  (Evidence Level EL-1)
22.214.171.124. Radiotherapy: Infradiaphragmatic para-aortic ± ipsilateral iliac nodes , (EL-1)
126.96.36.199. Surveillance: This should be done only in compliant patients with primary tumors < 4 cm and < pT2  (EL-1)
4.1.2. Stage is: The patients should offered radiotherapy to infradiaphragmatic para-aortic lymph nodes (EL-3)
4.1.3. Stage IIA and IIB:
188.8.131.52. Radiotherapy to infradiaphragmatic para-aortic and ipsilateral Iliac nodes  (EL-2)
184.108.40.206. For Stage IIB, chemotherapy with four cycles of etopodice and cisplatin (EP) or three cycles of bleomycin, etoposide, and cisplatin (BEP) could be given in a case where the radiotherapy toxicity is high (EL-2)
4.1.4. Stage IIC and III: Treatment will depend on the risk classification:
220.127.116.11. Good risk: Chemotherapy with four cycles of EP (for patients with compromised lung function), or three cycles of BEP , (EL-1)
18.104.22.168. Intermediate risk: Chemotherapy with four cycles of BEP  (EL-1).
4.1.5. Management of postchemotherapy residual nodes/masses seen on CT scan: This depend on the size and the level of tumor markers (hCG).
22.214.171.124. If size <3 cm and normal markers: Surveillance.
126.96.36.199. If more than 3 cm and normal markers: Do positron emission tomography scan: 
188.8.131.52.1. If negative: Surveillance (EL-2).
184.108.40.206.2. If positive consider one of the following options:
220.127.116.11.2.1. Surgical resection.
18.104.22.168.2.2. Second-line chemotherapy if positive for residual disease (See item 22.214.171.124.2)
126.96.36.199. If the residual mass is enlarging or markers increasing: Second-line chemotherapy (EL-2) - See item 188.8.131.52.2.
4.1.6. Management of patients failing 1 st line chemotherapy: Patients will receive second line chemotherapy; options are
184.108.40.206. Four cycles of vinblastin, ifosfafide and cisplatin (VeIP) regimen  (EL-2) or
220.127.116.11. Four cycles of paclitaxel, ifosfamide and cisplatin (TIP) regimen  (EL-2).
4.1.7. Management of patients failing second-line chemotherapy: Patients will be treated with combination paclitaxel and Gemcitabine for those who did not receive paclitaxel before. 
4.2. Nonseminoma: 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 follow:
4.2.1. Stage I:
18.104.22.168. Treatment will depend on the presence of any the following risk factors: 
22.214.171.124.1. Lymphovascular invasion.
126.96.36.199.2. Presence of emberyonal histology (50% or more). 
188.8.131.52.3. Absence of yolk sac histology.
184.108.40.206.4. Tumor stage > T1.
` 220.127.116.11. Stage I with no risk factors: Options are:
18.104.22.168.1. Surveillance: Should be reserved in compliant patients , (EL-2).
22.214.171.124.2. Two cycles of adjuvant chemotherapy with BEP regimen ,, (EL-1).
126.96.36.199.3. Open nerve sparing retroperitoneal lymph node dissection (RPLND): To be done only in high volume tertiary care centers  (EL-2): Further therapy will depend on the pathological result as follow:
188.8.131.52.3.1. pN0: Surveillance.
184.108.40.206.3.2. pN1: Surveillance in compliant patients or two cycles of chemotherapy with BEP in noncompliant patients (EL-3).
220.127.116.11.3.3. pN2-3: Three cycles of chemotherapy with BEP regimen (EL-3).
18.104.22.168. Stage I with any risk factor of above: Options are:
22.214.171.124.1. Two cycles of adjuvant chemotherapy with BEP regimen. 
126.96.36.199.2. Open nerve sparing RPLND: To be done only in high volume tertiary care centers  (EL-2): Further therapy will depend on the pathological stage as in item 188.8.131.52.3.
184.108.40.206. Stage Is: Patient should receive three cycles of systemic chemotherapy with the BEP regimen (EL-3).
4.2.2. Stage IIA and IIB: Options of therapy will depend if markers (AFP and hCG) are normal or elevated:
220.127.116.11. Normal markers: Options are:
18.104.22.168.1. Primary chemotherapy with three cycles of BEP. 
22.214.171.124.2. Open nerve sparing RPLND, , if the nodal metastasis is in the primary landing zone in selected patients. It should be done only in high volume center by experienced uro-oncologist. Further therapy will depend on the pathological stage as in item 126.96.36.199.3.
188.8.131.52. Elevated markers: Systemic chemotherapy depending on the international risk classification group:
184.108.40.206.1. Low risk: Three cycles of BEP. ,
220.127.116.11.2. Intermediate and high risk: Four cycles of BEP. 
4.2.3. Stage IIC and III: Treatment will be with chemotherapy depending on the international risk classification.
18.104.22.168. Low risk: Three cycles of BEP chemotherapy. ,
22.214.171.124. Intermediate and high risk: Four cycles of BEP chemotherapy. 
4.2.4. Management of postchemotherapy:
126.96.36.199. No residual disease and normal markers: Surveillance. 
188.8.131.52. No residual disease and elevated markers (AFP and hCG): Second line chemotherapy. See item 184.108.40.206.2.
220.127.116.11. Residual disease by CT scan ( > 1 cm): This depend on the level of serum markers:
18.104.22.168.1. Normal markers: RPLND and resection of all residual disease if technically feasible: , further therapy will depend on pathology result:
22.214.171.124.1.1. Mature teratoma, necrosis, or fibrosis: no further therapy.
126.96.36.199.1.2. Residual germ cell tumor: Two cycles of chemo therapy  with EP, VIP or TIP (see below) (EL-2).
188.8.131.52.2. Elevated markers: Second line chemo therapy; options are
184.108.40.206.2.1. Four cycles of VeIP regimen. 
220.127.116.11.2.2. Four cycles of TIP regimen. 
4.2.5. Management of patients failing second line chemotherapy: Patients will be treated with paclitaxel and Gemcitabine if did not receive paclitaxel before. 
4.2.6. 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. 
| References|| |
|1.||International Germ Cell Consensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997;15:594-603. |
|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. |
|3.||Fosså 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. |
|4.||Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, et al. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I Testicular Seminoma: A report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol 2005;23:1200-8. |
|5.||Warde PR, 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? J Clin Oncol 2005;23:382S. |
|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. |
|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. |
|8.||Toner GC, Stockler MR, Boyer MJ, Jones M, Thomson DB, Harvey VJ, et al. 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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|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. |
|25.||Fizazi K, Tjulandin S, Salvioni R, Germà-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. |
|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. |