Specific Rehabilitation Needs in

Testicular Cancer Survivors (TCSs)

Sophie D. Fosså

National Resource Center for Long-term Studies after Cancer

Oslo University Hospital

The Norwegian Radium Hospital

Oslo, NORWAY

Disposition

• Background

• Long-term Adverse Effects (AEs)

• Quality of Life

• Rehabilitation needs/tasks

Sources

• Literature

• Own experience (1400 TCSs surveyed in

~2000 and ~2008)

Background

• Testicular Cancer (TC):Peak incidence age 20-40 years

• Overall long-term survival: >95%

• Today several risk-adapted treatment options with a different risk profile of AEs to be discussed with the patient pre-treatment (start of rehabilitation)

Method• Group-wise evaluation

• General population comparison

Domains at risk

Life-threatening:

• Cardiovascular

• Second cancer

Quality of Life affecting

• Neuro-ototoxicity

• Gonadotoxicity (fertility/hormones)

• Psycho-social/Cognitive/Life style/Quality of Life

Cumulative risk (%) of developing a

second solid non-germ cell cancer

for seminoma or non-seminoma

and the general male population

20yrsNew ca :70 yrs

40%vs20%

Travis/Fosså JNCI 2005

35yrsNew ca: 70 yrs

30%vs15%

Second solid non-germ cell cancer

Bilateral metachronous invasive testicular cancer

Influence of chemotherapyNRH: 1980-1998; 54 of 1650 pts.

No Chemotherapy

Chemotherapy

P:0.02

Months since unilateral test.ca.

0 60 120 180 240 300

Pro

bal

ity

of

con

tral

ater

al t

est.

ca.

.07

.06

.05

.04

.03

.02

.01

0.00

Treatment for TC and risk of

cardiovascular diseases (CVD)(Surgery only as reference)

RR (95% CI)

Infarctus

CVD cordis

Chemotherapy only

PVB

BEP

1.9 (1.2-2.9)

1.5 (1.0-2.2)

1.9 (1.7-2.0)

1.2 (0.7-2.1)

Radiotherapy only

Mediastinal

Infradiaphragmatic

3.0 (2.0-4.5)

1.2 (0.8-1.7)

3.7 (2.2-6.2)

1.1 (0.7-1.7)

van den Belt-Dusebout AW, et al. JCO 2006; 3, 467

Odds Ratio of having hypertension

age-adjusted

Sagstuen , ESMO 2004

N: 1289 Norwegian Testicular

cancer survivors

Follow-up: Median 11 years

National survey: 1999-2001

Cancer testis:CRP >1.5 tatt 10 år etter behandling

predikerer ny kreft eller CVD 10 år deretter

121086420

Years after FU-1

0,16

0,14

0,12

0,10

0,08

0,06

0,04

0,02

0,00

Cu

mu

lati

ve

In

cid

en

ce

Non-germ cell cancer

p = 0.01

CRP ≥ 1.5 mg/L

CRP < 1.5 mg

121086420

Years after FU-1

0,12

0,10

0,08

0,06

0,04

0,02

0,00

Cu

mu

lati

ve

In

cid

en

ce

Cardiovascular events

p = 0.003

CRP ≥ 1.5 mg/L

CRP < 1.5 mg/L

Wethal, EJC, in press

van den Belt-Dusebout AW, et al. JCO 2007

Second Cancer /

Cardio-vascular

disease

and

Treatment modality

Initial treatment and risk of

second cancer / CVD

HR 95% CI

Surgery only 1

Subdiaph.RT only* 2.6 1.7-4.0

Subdiaph.+ mediast.RT* 3.6 2.1-6.0

Cispl.based chemoth.only 2.1 1.4-3.1

SMOKING 1.8 1.4-3.1

*Tendency for dose-effect relationship (p:0.055)

van den Belt-Dusebout (2007)

Quality of Life aspects

Prevalence of self-reported typical

post-treatment symptoms (11 year)

AE SURV1 RPLND2 RAD3 CHEM4

Peripheral neuropathy 10% 11% 16% 21%

Tinnitus 16% 14% 13% 22%

Diarrhoea 21% 25% 29% 29%

Impaired sexual function 13% 20% 23% 24%

1Surveillance, 2Retrop.lymph node dissection only , 3Radiotherapy only , 4Chemotherapy +/- Surgery/Radiotherapy

Mykletun,JCO,23:3061(2005)

Prevalence of patients with clinically

relevant worsening (≥10% of a scale 1-100))

after chemotherapy

*Skaali,Psycho-oncology 2009;18:580

2 year 11 year

Peripheral neuropathy 22% 18%

Tinnitus 26% 22%

Difficulty hearing 21% 21%

Sexual interest ↓

Sexual activity ↓

12%

14%

Relapse anxiety 17% 24%*

24%

→ No improvement of AEs after 2 years

11 year TCSs : Risk factors for poor

Quality of life (multivariate analysis

compared with gen.pop.)

Falk Dahl,JCS, in press

Prevalence

TCSs Norm OR

Not working 10% 9% 4.08

Musculo-skeletal probl. 35% 41% 2.55

Anxiety/Depression 22% 18% 2.77

Low-self esteem 21% 18% 2.35

Neurotoxic symptoms 2.26

Fatigue 28% 10% 7.13

Hearing loss

0

5

10

15

20

Months since chemotherapy start

Score

Tinnitus

0

10

20

30

40

50

Months since chemotherapy start

Score

0 3 6 12 24

0 3 6 12 24

Influence of days per cycle during 4 cycles cisplatin-based chemotherapy

1. Equally effective; 2. More ototoxicity during 2 days; 3. Chemotherapy

to be given during 5 days

2 days

5 days

Fosså,JCO 2003

OTOTOXICITY1 due to ciplatin based chemotherapy ( 4 cycles)

1Self-reported

0 %

20 %

40 %

60 %

80 %

100 %

Surg

/RT

<=4k

urer

>=5k

urer

dosei

ntens

poor

less good

quite good

very good

Audiometry

chi kvadrat p<0.001

Brydøy et al., in preparation

Figure 2A. Proportions with concentration problems

0

10

20

30

40

50

60

BASELINE 3 MONTHS 12 MONTHS

Per

cen

t

CHEM

RAD

Figure 2B. Proportions with memory problems

0

10

20

30

40

50

60

BASELINE 3 MONTHS 12 MONTHS

Per

cen

t

CHEM

RADFigure 2C. Proportions with cognitive function

problems

0

10

20

30

40

50

60

BASELINE 3 MONTHS 12 MONTHS

Per c

en

t

CHEM

RAD

Concentration

Memory

Cognitive function

Proportion of

Testicular Cancer

patients with self-reported

COGNITIVE COMPLAINTS

during the first post-orchiectomy

year and

using EORTC QL C-30

BEP chemotherapy x 3-4

( N = 276 )

Radiotherapy only

(N = 71 )

Skaali, submitted

Predictive factors for the development of self-reported cognitive complaints among 122 orchiectomized testicular cancer patients undergoing neuropsychological tests before and 1 year after treatment :

Chemotherapy

Low level of education

Mental problems prior to TC

Fatigue after 1 year

Raynaud-like symptoms

No relation between cognitive complaints

and neuropsychological tests at 1 year

Skaali, submitted

COGNITIVE FUNCTION

0

5

10

15

20

25

30

1 2 3 4 5Controls Surgery Rad. Chem+ Chem+

only only ≤850 >850

%

190

229

433

303

70

Hypogonadism in long-term TCSs

Gonadal function and fertility

Treatment- and cancer-related

biochemical hypogonadism

in 10-16%

Clinical relevance?Metabolic

Syndrome

Clinical hypogonadism in 4-5%

Optimal substitution?

Nord , Eur.Urol.(2003),44,322

100

Ach

ieve

dfa

ther

ho

od

%

80

60

40

20

0

Years from orchiectomia to first born child

Fertility: Post-treatment paternity in patients

attempting fatherhood

1. Treatment-and cancer-

related sub-fertility, but

70-80% father a child

post-treatment if attempted,

dose-effect relation

2. Limited use (30/430)

of frozen semen

16 pregnancies

BrydøyJNCI, 2005,Magelssen Eu.Urol.2005

BUT

Possibly increased

risk of slight

malformations

of the first child

born after cancer

in pre-diagn.childless

men

30

40

50

60

70

80

90

100

PF RP BP GH VT SF RE MH PCS MCS

SF

-36 sco

res

TCS

Norm

PF Physical Functioning, RP Role Physical, BP Bodily Pain, GH General Health, VT Vitality, SF Social

Functioning, RE Role Emotional, MH Mental Health, PCS Physical composite score, MCS Mental

Composit Score. Norm-data are age-adjusted to mach the TCS.

* p<.05

*

*

*

*

*

0

10

20

30

40

0

10

20

0

10

20N

um

ber

of

pa

tien

ts

wit

h m

ajo

r p

rob

lem

s (%

)

DRIVE Probl.

Ecaculation

Probl.

Satisfied

QUALITYof LIFE ( QoL) and SEXUALITY in Testicular cancer survivors

(after 11 yrs) and the General male population ( <40yrs old)

Phys.

QoL

Mental

QoL

Quality of life Sexual life

Dahl/Fosså (2005/2007)

Life styleSelf-reported Physical Activity in ≤5 year

Testicular Cancer Survivors

Pre-treatment Post-treatment

Total

139

Inactive

60 (43%)

Active

79 (57%)

Inactive

49 (82%)

Active

11 (18%)

Active

55 (70%)

Inactive

24 (30%)

Active

66 (47%)

Inactive

73 (53%)

Overall development

Inactivity: 43% → 53%

Activity: 57% → 47% Gjerset, in prep.

+

+

Specific rehabilitation tasks in

individual TCSs

Second cancer: Testicular self-examination / ultra-sonography in high-risk patients. Early specialist referral if symptoms suspicious of new cancer

Cardiovascular: Regular check-ups by family doctor (Lipids, blood pressure, weight, life style)

Gonadal: Cautious testosterone substitution Assisted reproduction, Testicular prosthesis??

(→ bilateral TC)

Neuro-/ototoxicity: 5-days BEP, evtl. change of occupation

Life style: Physical activity

Conclusion

Specific therapeutic rehabilitation task

needed in the minority of TCSs (15-20%?)

Prevention of second cancer and

cardiovascular disease necessary

Thank you

Cisplatin-based chemotherapy delays the

development of invasive cancer, but does not abolish

the risk completely

1,2

1,0

0,8

0,6

0,4

0,2

0,0

-,2Pro

bab

ilit

y o

f in

vas

ive

test

.can

cer

Months since diagnosis of testicular CIS

Invasive test.cancer from CIS:Influence of chemotherapy (NRH: 1980-2001)

Chemotherapy

No Chemotherapy

0

1

2

3

4

1 2 3 4 5 6 7 8 9

RR

Relative risk of second solid cancer after

treatment of testicular cancer at an age of 35 years

(~ 40 000 patients, 1943-2002)

All 1 2 3 4 5 6 7 8

Travis/Fosså, JNCI 2005

1. Stomach 5. Colon

2. Pancreas 6. Rectum

3. Bladder 7. Mal.melanoma

4. Kidney 8. Lung

1694

129

95

21180

153101 70

256

30

40

50

60

70

80

90

100

PF RP BP GH VT SF RE MH PCS MCS

SF

-36 s

co

res

TCS

Norm

PF Physical Functioning, RP Role Physical, BP Bodily Pain, GH General Health, VT Vitality, SF Social

Functioning, RE Role Emotional, MH Mental Health, PCS Physical composite score, MCS Mental

Composit Score. Norm-data are age-adjusted to mach the TCS.

* p<.05

*

*

*

*

*

Quality of life (SF-36) in 1409 Norwegian males

treated for testicular cancer 1980-1994

(median obs.time ~11years)

Physical

health

Mental

health

Long-term cognitive function following chemotherapy

in patients with testicular cancer.

Pedersen AD, Rossen P, Mehlsen MY,

Pedersen CG, Zachariae R, von der Maase H.

'J Int Neuropsychol Soc.');2009 Mar;15(2):296-301. Epub 2009 Feb 10.

there was no difference in the proportion

of cognitively impaired patients

in the chemotherapy group (5.6%) compared to the

nonchemotherapy group (8.3%) (chi2 = 0.22, p = .64).

20-30% have complaints

Cumulative risk (%) of developing a second solid non-

germ cell cancer at age 70 years for seminoma ,

and the general male population

20yr2nd. ca :70yr

ca. 40% vs 20%

Travis/Fosså JNCI 2005

35year2nd. ca: 70 yr

30% vs 15%

Second Cancer

Second germ cell malignancy

(Contralateral Testicular Cancer [CTC])

Testicular dysgenesis syndrome (TDS) during embryonal

life (Week 4-8)

→ Testicular cancer in situ

Other manifestations and

clinical risk groups for CTC:

- Hypospadia

- Cryptorchidism

- Infertility

- Contralateral cancer in situ (5% of unilat.TC, 30% of

extragonadal germ cell cancer )

Testicular ca.in situ Crude % of invasive CTC1

Mean Range

Synochronuous: 0.5% 0.2-0.8%

Metachronuous: 1.2% 0.8-2.7%

15 year SIR

SEER 1.9% (1.7%-2.1%)

Netherland 2.4% (1.4%-3.9%)

Norway 3.9% (2.8%-5%)

20 year

Denmark 5.2% (3.7%-6.7%)

Fossa ,JNCI

( 2005),97;10561Contralateral Testicular Cancer,Large geographical differences

Highest risk during the first 5 years

Risk factors: SEMINOMA (No chemotherapy)

Age <30 years at first TC