Testicular Cancer. Prof. Dr. Jörg Beyer Physician-in-Chief Department of Oncology, University Hospital Berne, Switzerland. Mail:

Transcription

1 Testicular Cancer Prof. Dr. Jörg Beyer Physician-in-Chief Department of Oncology, University Hospital Berne, Switzerland Mail:

2 The menue: Epidemiology & Staging Ongoing discussions & risk-adapated treatment Focus on early stage disease Little on advanced/poor risk disease Little on relapsed or refractory disease Some emphasis on survivorship care Full presentation via the ESO webpage

3 Testis cancer in Europe 2012 Incidence Mortality

4 All pts. treated in Denmark between Mortensen Eur Urol 2014 Daugaard J Clin Oncol 2014 Kier Eur Urol 2016

5 Take home message Germ-cell cancer is the most frequent cancer in men age years. About 3% are primary extragonadal.

6 Initial Staging + H & P, physical examination including testes + Testicular ultrasound + Tumormarker AFP, HCG and LDH (no PLAP) + CT thorax and abdomen +/- CT/MRI brain (only if pulmonary metastases present) - No PET CT scans!!

7 Tumor size, rete testis involvement Seminoma vs Non-seminoma or mixed tumors In non-seminoma: is there teratoma present Evidence of lymphovascular invasion

8 Take home message About 70% of patients present as clinical stage I.

9 Slide at the courtesy of Prof. Loy, Berlin Vascular invasion - must be stated in the pathology report - needs an experienced pathologist - is helped by anti CD 31 immunohistology - must be obvious in the section

10 Cancer Medcine 2014, doi: /cam4.324

11 Case No 1: 33 years Testicular cancer Orchiectomy => pure seminoma Size 4 cm, no infiltration rete testis or vascular invasion AFP und HCG normal LDH prior orchiektomy 480 U/L LDH post orchiektomy normal CT thorax & abdomen w/o LN metastases

12 Stage according Stadieneinteilung to the UICC nach UICC classification Stadium III M1a = med. / cerv. Lk. oder pulmonale Met. M1b = extr. pulm. Met. Stadium II N1 = abd. Lk. < 2 cm N2 = abd. Lk. 2-5 cm N3 = abd. Lk. > 5 cm Stadium I nur im Hoden

13 Case No 1: 33 years Testicular cancer Orchiectomy => pure seminoma Size 4 cm, no infiltration rete testis or vascular invasion AFP und HCG normal LDH prior orchiektomy 480 U/L LDH post orchiektomy normal CT thorax & abdomen w/o LN metastases Seminoma Stage I => Which treatment?

14 Abbildung 2: Strahlenfeld Seminom im Stadium I Radiation treatment Seminoma Stage I Dose 20 Gy Pro: long experience low relapse rate Con: acute & late toxicities secondary tumors

15 Update ASCO 2008 AUC 7 cave: avoid undertreatment, no capping Lancet 2005; 366:

16 Ann Oncol March 2013

17 Safe Relapse rate of 15-20% in seminoma Almost all relapses can be salvaged by BEP x 3 Overall survival close to 100% Only those who need treatment get treated Avoids adjuvant treatment in 80-85% of patients

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19 all patients with metastatic seminoma (stage II & III) should receive first-line chemotherapy with three rarely four * cycles of BEP * four cycles BEP in patients with bulky or extrapulmonary disease

20 3 Zyklen BEP every 21 days

21 No Bleomycin Age > 50 years Packyears > 20 years DLco < 60% of normal Restrictive lung disease (e.g. COPD) Poor renal function GFR < 80 ml/min

22 3 Zyklen BEP (4 Zyklen EP) every 21 days

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24 Only in Seminoma with residual tumor post chemotherapy PET - CT

25 Summary Current Treatment Strategies in Seminoma Ca. 80% of patients present as stage I "Active Surveillance the new standard, alternatively one cycle adjuvant Carboplatin AUC 7. Adjuvant radiation no longer recommended. Histologie! Ca. 20% of patients present with metastastic disease Standard treatment with three (rarely four) cycles BEP Careful with bleomycin in poor pulmonary & renal function & older age No residual tumor resection after chemotherapy! Residual tumors after chemotherapy rare indication for PET-CT scans

26 Case No 2: 36 years Testicular cancer Orchiectomy, mixed NSGCT, 80% EC. Size 4 cm, no vascular invasion CT thorax and abdomen w/o metastases AFP U/L, HCG 10 U/L prior orchiectomy

27 Case No 2: 36 years Testicular cancer Orchiectomy, Mixed NSGCT, 80% EC. Size 4 cm, no vascular invasion CT thorax and abdomen w/o metastases AFP U/L, HCG 10 U/L prior orchiectomy AFP 560 U/L, HCG normal post orchiectomy

28 Case No 2: 36 years Testicular cancer Orchiectomy, Mixed NSGCT, 80% EC. Size 4 cm, no vascular invasion CT thorax and abdomen w/o metastases AFP U/L, HCG 10 U/L prior orchiectomy AFP 560 U/L, HCG normal post orchiectomy AFP 140 U/L, HCG normal after 2 weeks AFP 64 U/L, HCG normal after 3 weeks AFP normal, HCG normal after 35 days

29 Case No 2: 36 years Testicular cancer Orchiectomy, mixed NSGCT, 80% EC. Size 4 cm, no vascular invasion CT thorax and abdomen w/o metastases AFP U/L, HCG 10 U/L prior orchiectomy Normalization of tumor markers post orchiectomy Non-Seminoma CS I => Which treatment?

30 Stage according Stadieneinteilung to the UICC nach UICC classification Stadium III M1a = med. / cerv. Lk. oder pulmonale Met. M1b = extr. pulm. Met. Stadium II N1 = abd. Lk. < 2 cm N2 = abd. Lk. 2-5 cm N3 = abd. Lk. > 5 cm Stadium I nur im Hoden

31 14% Relapses 48% Relapses Eur Urol cycle 1 cycle

32 Safe Relapse rate of 15-50% in non-seminoma Almost all relapses can be salvaged by BEP x 3 (-4) Overall survival close to 100% Only those who need treatment get treated Avoids adjuvant treatment in 80-85% of patients

33 Summary Current Strategies in Non-Seminoma Ca. 60% of patients present as clinical stage I "Surveillance in "low risk" patients without vascular invasion in the primary tumor, one cycle adjuvant BEP in "high risk" patients with evidence of vascular invasion in the primary tumor

34 Case No 3: 36 years Lumberjack Increasing shortness of breath at work Went to the A & E of his local hospital Pleural mass and multiple pulmonary metastases

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36 Case No 3: 36 years Increasing shortness of breath at work Pleural mass and multiple pulmonary metastases Admitted to pulmonary service of the local hospital Thoracic CT scan and bronchoscopy Undifferentiated cancer compatible with NSCLC

37 Case No 3: 36 years Increasing shortness of breath at work Pleural mass and multiple pulmonary metastases Admitted to pulmonary service of the local hospital Thoracic CT scan and bronchoscopy Undifferentiated cancer compatible with NSCLC Carboplatin, gemcitabine & bevacizumab Staging PET CT scan after first cycle

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41 Case No 3: 36 years Increasing shortness of breath at work Pleural mass and multiple pulmonary metastases Admitted to pulmonary service of the local hospital Thoracic CT scan and bronchoscopy Undifferentiated cancer compatible with NSCLC Carboplatin, gemcitabine & bevacizumab Staging PET CT scan after first cycle AFP ng/ml, LDH 834 U/l, HCG normal

42 Overall Survival > 90 % Overall Survival ~ 78 % Overall Survival ~ 45 %

43 Case No 3: 36 years Patient with extensive disease germ-cell cancer High risk of first-line failure & treatment related death - poor performance status - poor pulmonary & renal function - high risk of sepsis and multiorgan failure - high incidence of cns metastases - fatal bleeding from ruptured metastases - fatal pulmonary embolism

44 Impact of Center Expertise on Surival in Patients with "poor prognosis" Germ-cell Cancer Influence of center experience on "failure-free survival" in poor prognosis germ-cell tumor EORTC/MRC trial 5-9 Pat Pat. > 19 Pat. < 5 Pat. Collette et. al J Natl. Cancer Inst p < 0.018

45 All patients with metastastic Non-Seminoma should receive first-line chemo with three to four cycles BEP Standard first-line treatment regimens days days days No dose reduction or treatment delay for uncomplicated cytopenias. No routine G-CSF or other growth factors. In patients with dyspnoe or pneumonia check for bleomycin toxicity, before continuation with BEP

46 Randomized trials using upfront HDCT n=219, JCO 2007, Motzer et al. Intergroup trial USA Started 1997 Published 2007 No benefit from upfront HDCT R n=131, Ann Oncol 2011, Daugaard et al. EORTC GU Europe PEB PEB PEB PEB Started 1999 R Published 2011 No benefit from upfront HDCT PEI PEI PEI PEI

47 Fizazi et al. Lancet 2014

48 Do resect all residual lesions > 1 cm after chemotherapy in non-seminoma! may contain vital cancer (more frequent than in seminoma) may contain teratoma (does not exist in seminoma) PET scans are useless in non-seminoma! Do not resect resdiual lesions in seminoma!

49 Pre BEP x 3 Post BEP x 3

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51 Summary Current Strategies in Non-Seminoma Ca. 60% of patients present as clinical stage I "Surveillance in "low risk" patients without vascular invasion in the primary tumor, one cycle adjuvant BEP in "high risk" patients with evidence of vascular invasion in the primary tumor Histologie! Ca. 40% of patients present with metastatic disease Standard chemotherapy three to four cycles PEB according to risk. Resection of all residual tumor post chemotherapy. No role for PET-CT scans

52 Prognostic factors in relapsed/refractory GCC poor good Primary Tumor mediastinal gonadal Histology non-seminoma seminoma Respone 1 Line no CR/NED/PRm- CR/NED Histologie! Response duration short long Marker Level high low Metastatic location brain, bone, liver lymphnodes or lung Salvage attempt second or subsequent first-salvage

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54 Strategy for first-salvage Patienten Patients mit with Progress relapse or oder progression Rezidiv nach after chemotherapy Chemotherapie Indication for salvage surgery? Without Ohne Risikofaktoren risk factors Konventionell Conventional dose dosierte treatment Therapie With Mit Risikofaktoren risk factors Hoch High dosisierte dose Therapie treatment - Progression mature teratoma - late relapse > 2 years - resectable relapse after HDCT Risk factors - extragonadal primary tumor - no CR / PRm- after first-line - early relapse - extrapulmonary metastases - high AFP or HCG levels - any second or subsequent relapse

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57 Second solid non-germ cell cancer Diagnosis at 20y at age 70: 40% vs. 20% Modern radiotherapy: Reduced dose & field No of solid tumors RR (95%CI) Radiotherapy alone ( ) Chemotherapy alone ( ) Radioth. + Chemoth ( ) Travis/Fosså JNCI 2005

58 Metabolic syndrome in will develop in % of testicular cancer survivors de Haas et al,ann Oncol 2013

59 Basics of a survivorship plan Details on histology & intial stage Details on treatment delivered (drugs, schedules, modalities) Recommendation for a follow-up schedule (10 years) Risk of relapse only in the first 2-3 years Identify main individual long-term toxicities that might occur Give life-style recommendations Identify possible additional resources (e.g. support groups) Identify the person in charge for follow-up including contact information!

60 Summary testicular cancer Get exact histological information Get exact staging information Histologie! Follow the correct management algorithmus meticulously High cure rates even in metastatic tumor stages Manage patients only in interdisciplinary teams specifically dedicated to the management of testicular cancers!

61 Get experts involved German/Swiss/Austrian Group