|Year : 2016 | Volume
| Issue : 2 | Page : 141-145
Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for testicular germ cell tumors
Mohammed Alotaibi1, Ahmad Saadeddin2, Shouki Bazarbashi3, Sultan Alkhateeb4, Abdullah Alghamdi5, Khalid Alghamdi6, Esam Murshid7, Ashraf Abusamra8, Danny Rabah9, Imran Ahmad10, Mubarak Al-Mansour11, Abdullah Alsharm12
1 Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
3 Department of Oncology, Secti on of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4 Department of Surgery, Division of Urology, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
5 Department of Urology, Prince Sultan Medical Military Center, Jeddah, Saudi Arabia
6 Department of Surgery, Division of Urology, Security Forces Hospital, Jeddah, Saudi Arabia
7 Department of Oncology, Oncology Center, Prince Sultan Medical Military City, Jeddah, Saudi Arabia
8 Department of Surgery, Urology Section, King Khalid Hospital, King Abdulaziz Medical City, Ministry of Nati onal Guard Health Affairs, Jeddah, Saudi Arabia
9 Department of Surgery, College of Medicine and Uro-oncology Research Chair, King Saud University, Jeddah, Saudi Arabia
10 Department of Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
11 Department of Oncology, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
12 Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
|Date of Submission||08-Nov-2015|
|Date of Acceptance||15-Nov-2015|
|Date of Web Publication||23-Mar-2016|
Department of Surgery, Division of Urology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, P.O. Box: 22490 (1446), Riyadh 11426
| Abstract|| |
This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with testicular germ cell tumors. It is categorized according to the stage of the disease using the tumor-node-metastasis staging system 7th edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with testicular germ cell tumors.
Keywords: Cancer, germ cell, guidelines, management, Saudi Oncology Society, Saudi Urological Association, testicular, tumor
|How to cite this article:|
Alotaibi M, Saadeddin A, Bazarbashi S, Alkhateeb S, Alghamdi A, Alghamdi K, Murshid E, Abusamra A, Rabah D, Ahmad I, Al-Mansour M, Alsharm A. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for testicular germ cell tumors. Urol Ann 2016;8:141-5
|How to cite this URL:|
Alotaibi M, Saadeddin A, Bazarbashi S, Alkhateeb S, Alghamdi A, Alghamdi K, Murshid E, Abusamra A, Rabah D, Ahmad I, Al-Mansour M, Alsharm A. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for testicular germ cell tumors. Urol Ann [serial online] 2016 [cited 2020 Jul 2];8:141-5. Available from: http://www.urologyannals.com/text.asp?2016/8/2/141/179240
| Introduction|| |
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 multidisciplinary approach in managing testis cancer, the group recommended that all testicular cancer cases should be managed in tertiary care centers.
- The American Joint Committee on Cancer tumor-node-metastasis staging for testis cancer (7th edition 2010) was used.
- Evaluation of testicular tumors2.1. 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 should prior to orchiectomy
2.3. Computed tomography (CT) chest, abdomen, and pelvis should performed for confirmed testicular cancer.
- Risk stratification
- The International Germ Cell Cancer Collaborative Group risk classification.
- Treatment of testicular germ cell cancerGeneral considerations:
- Patients at all stages should undergo urgent inguinal orchiectomy unless the clinical situation requires immediate chemotherapy in patients with a testicular mass and clear germ cell malignancy based on elevated tumor markers
- Trans-scrotal biopsy or orchiectomy for any intra-testicular lesion is absolutely contra-indicated
- All patients who will undergo treatment with chemotherapy, retroperitoneal lymph node dissection (RPLND), or radiotherapy should be offered sperm banking. To maintain treatment intensity, chemotherapy cycles should be repeated every 3 weeks, independent of leukocyte count
- Tumor markers are to be determined immediately before the start of each new chemotherapy cycle.
The treatment will depend on the histological subtype as follow:
Further treatment will depend on the stage:
4.1.1. Stage I
220.127.116.11. Surveillance: Is considered the preferred strategy, except in patients with expected poor compliance or with primary tumor size ≥4 cm and ≥pT2 (evidence level [EL-1])
18.104.22.168. Chemotherapy: Single agent carboplatin: 1–2 doses at area under the curve 7 (EL-1)
22.214.171.124. Radiotherapy: Infradiaphragmatic para-aortic strip only and in patient with prior scrotal surgery, ipsilateral iliac nodes should be included (EL-1).,
4.1.2. Stage IS
126.96.36.199. Infradiaphragmatic radiotherapy to para-aortic strip only and in patient with prior scrotal surgery, ipsilateral iliac nodes should be included (EL-3).
4.1.3. Stage IIA and IIB, all of the following options are acceptable
188.8.131.52. Radiotherapy to infradiaphragmatic para-aortic and ipsilateral Iliac nodes, preferred for stage IIA and for stage IIB who are not fit for chemotherapy (EL-2)
184.108.40.206. Three cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy or four cycles of etoposide and cisplatin (EP), if there are concerns about bleomycin toxicity as in patients with reduction in lung capacity, emphysema, heavy smoking (including former smokers) (EL-2).
4.1.4. Stage IIC and III: Treatment will depend on the risk classification
220.127.116.11. Good risk: Three cycles of BEP chemotherapy or four cycles of EP, if there are concerns about bleomycin lung toxicity (EL-1)
18.104.22.168. Intermediate risk: Chemotherapy with four cycles of BEP or four cycles of VIP chemotherapy (etoposide, ifosfamide, and cisplatin) (EL-1).
4.1.5. Management of postchemotherapy residual nodes/masses seen on computed tomography 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:
188.8.131.52. If negative: Surveillance (EL-2).
184.108.40.206. If positive consider one of the following options:
220.127.116.11.1. Surgical resection
18.104.22.168.2. Second-line chemotherapy if positive for residual disease (see item 22.214.171.124.3.2)
126.96.36.199. If the residual mass is enlarging or markers increasing: Second-line chemotherapy (EL-2) - (see item 188.8.131.52.3.2).
4.1.6. Management of patients failing 1st line chemotherapy: Patients will receive second-line chemotherapy; options are:
184.108.40.206. Four cycles of vinblastine, ifosfamide, 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 monotherapy or combination of paclitaxel and gemcitabine (for those who did not receive paclitaxel before), gemcitabine and oxaliplatin, or oral etoposide.
Treatment will depend on the stage as follow:
4.2.1. Stage I
Treatment will depend on the presence of any the following risk factors: Lymphovascular invasion, presence of embryonal histology (50% or more), absence of yolk sac histology, and tumor stage > T1.,
18.104.22.168. Stage I with no risk factors, options are:
22.214.171.124.1. Surveillance: Should be reserved in compliant patients (EL-2).,
126.96.36.199.2. Two cycles of BEP regimen (EL-1),,, also one cycle of BEP chemotherapy can be considered in such cases 
188.8.131.52.3. Open nerve sparing RPLND to be done only in high volume tertiary care centers (EL-2), further therapy will depend on the pathological result as follow:
184.108.40.206.3.1. pN0: Surveillance
220.127.116.11.3.2. pN1: Surveillance in compliant patients or two cycles of chemotherapy with BEP in noncompliant patients (EL-3)
18.104.22.168.3.3. pN2-3: Three cycles of chemotherapy with BEP regimen (EL-3).
22.214.171.124. Stage I with any risk factor of above, options are:
126.96.36.199.1. Two cycles of adjuvant chemotherapy with BEPm regimen 
188.8.131.52.2. Open nerve sparing RPLND: To be done only in case of contraindication for chemotherapy and in high volume tertiary care centers (EL-2): Further therapy will depend on the pathological stage as in item 184.108.40.206.3.1-3.
220.127.116.11. Stage IS:
Patient should receive three cycles of systemic chemotherapy with the BEP regimen (EL-3).
18.104.22.168. Stage IIA and IIB: Options of therapy will depend if markers (AFP and hCG) are normal or elevated:
22.214.171.124.1. Normal markers, options are:
126.96.36.199.1.1. Primary chemotherapy with three cycles of BEP.
188.8.131.52.1.2. Open nerve sparing RPLND,, only if the nodal metastases is in the primary landing zone and 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 184.108.40.206.3.1-3.
220.127.116.11.2. Elevated markers: Systemic chemotherapy depending on the international risk classification group:
18.104.22.168.2.1. Low risk: Three cycles of BEP chemotherapy.,
22.214.171.124.2.2. Intermediate and high risk: Four cycles of BEP chemotherapy.
126.96.36.199. Stage IIC and III: Treatment will be with chemotherapy depending on the international risk classification
188.8.131.52.1. Low risk: Three cycles of BEP chemotherapy.,
184.108.40.206.2. Intermediate and high risk: Four cycles of BEP chemotherapy.
220.127.116.11. Management of postchemotherapy: Tumor markers and imaging with CT scan should be done 4–8 weeks after the last cycle of chemotherapy.
18.104.22.168.1. No residual disease and normal markers: Surveillance is recommended.
22.214.171.124.2. No residual disease and elevated markers: Second-line chemotherapy. See item 126.96.36.199.3.2
188.8.131.52.3. Residual disease by CT scan (>1 cm): This depends on the level of serum markers:
184.108.40.206.3.1. Normal markers: RPLND and resection of all residual disease, if technically feasible:, Further therapy will depend on pathology result:
220.127.116.11.3.1.1. Mature teratoma, necrosis, or fibrosis: No further therapy
18.104.22.168.3.1.2. Residual germ cell tumor: Two cycles of chemo therapy  with E P, VIP or TIP
(see below) (EL-2).
22.214.171.124.3.2. Elevated markers: Second-line chemotherapy options include
126.96.36.199.3.2.1. Four cycles of VeIP regimen.
188.8.131.52.3.2.2. Four cycles of TIP regimen.
184.108.40.206.3.2.3. High-dose chemotherapy with autologous stem-cell transplant.
- 5. Salvage treatment for seminoma and nonseminoma
5.1. Conclusive recommendations cannot be made at present
5.2. Prognosis is variable with 2 years survival rate ranging between 75% and 6% based on prognostic score
5.3. Options includes TIP × 4 or VeIP × 4 or high-dose chemotherapy with TI-CE mainly for patients at second-line setting
5.4. Carboplatin based high-dose chemotherapy as third line or later is an option, despite absence of randomized trials in this area
5.5. Desperation surgery should be part of the strategy whenever possible, particularly in patients with localized disease and with poor response to chemotherapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
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.
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.
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.
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.
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.
Horwich A. Radiotherapy in stage I seminoma of the testis. J Clin Oncol 2004;22:585-8.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pico JL, Rosti G, Kramar A, Wandt H, Koza V, Salvioni R, et al.
A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 2005;16:1152-9.
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.