Germ-cell cancer s a l c r e t s a M R B E E Prof. Dr. - - PowerPoint PPT Presentation

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Germ-cell cancer s a l c r e t s a M R B E E Prof. Dr. - - PowerPoint PPT Presentation

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9 1 0 2 s Germ-cell cancer s a l c r e t s a M R B E E Prof. Dr. Jrg Beyer O Physician-in-Chief M Medical Oncology S E Inselspital, Bern University Hospital - O University of Bern S E Mail: joerg.beyer@insel.ch 9

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Germ-cell cancer

  • Prof. Dr. Jörg Beyer

Physician-in-Chief Medical Oncology Inselspital, Bern University Hospital University of Bern Mail: joerg.beyer@insel.ch

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The menue:

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

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SLIDE 3

www.rki.de (Krebs in Deutschland Februar 2010)

Incidence Mortality

Incidence and Death Rates Testis Cancer in Europe

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Germ-cell cancer in Europe 2012 Incidence Mortality

http://eco.iarc.fr/eucan

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Stage according to UICC

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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 !!

expert patholgy assessment

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Cave

  • ca. 3% primary extragonadal

germ-cell cancers

  • no upfront orchiectomy in

widely metastatic disease

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

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Cancer Medcine 2014, doi: 10.1002/cam4.324

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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

Slide at the courtesy of Prof. Loy, Berlin

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Case No 1: 33 years

  • Testicular cancer
  • Orchiectomy => pure seminoma
  • Size 4 cm, no infiltration rete testis
  • AFP und HCG normal
  • LDH prior orchiectomy 480 U/L
  • LDH post orchiectomy normal
  • CT thorax & abdomen w/o LN metastases

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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 ?

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SLIDE 13

Ann Oncol March 2013

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  • 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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Stage I

All pts. treated in Denmark between 1984 - 2007 with active surveillance

Daugaard personal communication

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Why worry about giving 3 x BEP?

  • Lousy life during chemotherapy
  • Look like a zombie
  • Nothing is normal any more: fatigue,

nausea, vomitting, tinnitus, polyneuropathy, abnormal taste, Raynaud´s phenomenon

  • Rare, but life-threatening risks

bleomycin lung, thrombosis/pulmonary emboli

  • Off work for several months

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SLIDE 17

de Haas et al. Ann Oncol 2013

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SLIDE 18

Ann Oncol March 2013

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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

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3 Zyklen BEP (4 Zyklen EP) every 21 days

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Summary Current Treatment Strategies in Seminoma

Histologie !

  • 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.

  • 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

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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 1.480 U/L, HCG 10 U/L prior orchiectomy

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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 1.480 U/L, HCG 10 U/L prior orchiectomy
  • AFP 560 U/L, HCG normal post orchiectomy

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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 1.480 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

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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 1.480 U/L, HCG 10 U/L prior orchiectomy
  • Normalization of tumor markers post orchiectomy

Non-Seminoma CS I => Which treatment ?

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Ann Oncol 2017

14% Relapses 48% Relapses

1 cycle 1 cycle

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  • 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

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Stage I

All pts. treated in Denmark between 1984 - 2007 with active surveillance

Daugaard personal communication

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Summery Current Strategy in Non-Seminoma

Histologie !

  • 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

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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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SLIDE 31

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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

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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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SLIDE 34

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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 138.000 ng/ml, LDH 834 U/l, HCG normal

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

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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

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Influence of center experience on "failure-free survival" in poor prognosis germ-cell tumor

< 5 Pat. > 19 Pat. 10-19 Pat. 5-9 Pat.

p < 0.018 EORTC/MRC trial

Impact of Center Expertise on Surival in Patients with "poor prognosis" Germ-cell Cancer

Collette et. al J Natl. Cancer Inst. 1999

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All patients with metastastic Non-Seminoma should receive first-line chemo with three to four cycles BEP

No dose reduction or treatment delay for uncomplicated cytopenias. No routine G-CSF or other growth factors. In patients with dyspnoe

  • r pneumonia check for bleomycin toxicity, before continuation with BEP

Standard first-line treatment regimens

days days days

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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 !

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Pre BEP x 3 Post BEP x 3

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Summery Current Strategy in Non-Seminoma

Histologie !

  • 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

  • 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 of PET-CT scans

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Prognostic factors in relapsed/refractory GCC

Histologie !

poor good

  • Primary Tumor

mediastinal gonadal

  • Histology

non-seminoma seminoma

  • Respone 1° Line

no CR/NED/PRm- CR/NED

  • 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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Ohne Risikofaktoren Patienten mit Progress oder Rezidiv nach Chemotherapie Konventionell dosierte Therapie Mit Risikofaktoren Hoch dosisierte Therapie

Indication for salvage surgery?

  • 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

Strategy for first-salvage

Patients with relapse or progression after chemotherapy Without risk factors With risk factors Conventional dose treatment High dose treatment

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Metabolic syndrome in will develop in 20-30 % of testicular cancer survivors

de Haas et al,Ann Oncol 2013

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Travis/Fosså JNCI 2005

Second solid non-germ cell cancer

Diagnosis at 20y at age 70: 40% vs. 20%

No of solid tumors RR (95%CI) Radiotherapy alone 892 2.0 (1.9-2.2) Chemotherapy alone 35 1.8 (1.3-2.5)

  • Radioth. + Chemoth.

25 2.9 (1.9-4.2)

Modern radiotherapy: Reduced dose & field

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  • 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!

Basics of a survivorship plan

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Summary

Histologie !

  • Get exact histological information
  • Get exact staging information
  • 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 germ-cell cancers !

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