31 - testicular cancer Flashcards
testicular ca RR and undescended testicle
6 x rr
RR of contralateral testicle ca in undescended testicle
1.7 x RR
tca and age of orchiopexy
increased risk the later in age of orchiopexy
greatest risk of testis cancer is?
prior history of testis ca
relative risk of germ cell testis ca with prior hx germ cell ca
25 x RR
3 genetic syndromes assd w testicular ca
- kleinfelter (47 xy), 2. mullerian duct syndrome, 3. downs
2 prenatal RF for testis ca
- estrogen exposure, 2. inverse relationship with birth order
where does ITGCN arise from in testicle
spermatogonia
genetic finding that is diagnostic of GCT
presence of extra copies of short arm of chr 21
do the majority of seminomas secrete hcg?
no
tumor marker found in seminoma
HCG - only 20%
what cells secrete HCG
synctiotrophoblasts
tumor markers in embryonal carcinoma
hcg and afp
tumor marker in yolk sac
AFP
pathognomonic finding in yolk sac
schiller-duval bodies
choriocarcinoma tumor marker
HCG
feature of choriocarcinoma tumor marker
very high HCG level
clinical feature of choriocarcinoma
small primary, wide spread hematologic mets (brain/ lungs)
malignant potential of teratoma in children
benign
when is teratoma found in adults
NSGCT
% gct are mixed
30-50%
malignant potential of epidermoid cyst
benign
what lines epidermoid cysts
squamous epithelium
mgmt of suspected epidermoid cyst
do open biopsy/ partial orchiectomy. if epidermoid cyst confirmed, then close. if malignant, orchiectomy
major difference between seminoma and nonseminoma and treatment
only nonseminoma can have teratoma, which has to be eradicated
afp half life
5 days
hcg half life
24-36 hrs
2 tumors producing AFP
embryonal and yolk sac
nl function of HCG
produced by placenta to maintain corpus luteum in pregnancy
low testosterone and tumor markers
high LH can cross react with HCG
HCG homologous to what other protein
b-subunit of LH
how to manage aberrantly elevated LH
give testosterone shot and re-test hcg
signifance of nl tumor markers
does not gaurantee eradication of all cancer cells
drainage of retroperitoneal lymphatics
mediastinum then chest
GCT clinical stage 1
all disease confined to testicle w nl tumor markers after orchiectomy
GCT clinical stage 1s
same as CS1 with elevated post orchectomy markers
NSGCT CS1s mgmt
chemo
clinical stage 2a vs 2b vs 2c for sem and non-sem germ cell tumor
retroperitoneal disease < 2 cm, 2-5 cm, > 5 cm
GCT clinical stage 3
supradiaphragmatic (including lungs) or visceral mets
tumor primary location and risk stratification in GCT
good and intermediate risk gonadal/retroperitoneal primary, poor risk is mediastinal or non-pulmonary visceral mets
AFP and risk stratification in GCT
good risk < 1000, intermediate risk 1000-10,000, poor risk > 10,000
HCG and risk stratification in GCT
good risk < 5000, intermediate risk, 5000-50,000, poor risk > 50,000
LDH and risk stratification in GCT
good risk > 1.5x nl, intermediate risk 1.5-10x nl, poor risk > 10x nl
good risk criteria
- gonadal/retroperitoneal primary, 2. no non-pulmonary mets, 3. AFP < 1000, HCG < 5000, LDH > 1.5 x nl
intermediate risk criteria
- gonadal/ retroperitoneal primary, 2. no non-pulm visceral mets, 3. AFP 1000-10,000, HCG - 5,000 - 50,000, LDH 1.5 x - 10x nl
poor risk criteria
any of the following: 1. mediastinal primary, 2. non-pulm visceral mets, 3. AFP > 10,000, HCG > 50,000, LDH > 10x nl
5 yr survival for good risk
90%
5 yr survival for intermediate risk
80%
5 yr survival for poor risk
50%
treatment for good risk
BEP x 3
when is BEP x 3 not given for good risk - 2
smoking hx and older pts
what to give instead of BEP x 3 in good risk
EP x 4
2 options for chemo in intermediate risk
BEP x 4 or BEP x 3 + EP x 1
poor risk chemo
BEP x 4 only
3 reasons for inguinal vs scrotal orchiectomy
- lower chance of cutting into tumor by accident, 2. removal of lymphatics draining primary, 3. prevent aberrant lymphatic drainage if tumor is spilled
partial orchiectomy indications
- contralateral abscent testis, 2. tumor < 2 cm, 3. polar tumor location
when to do adjuvant radiation in partial orchiectomy
if CIS present - done to reduced recurrence if done routinely
adjuvant tx post partial orchiectomy
20 gy to eradicate CIS
purpose of partial orchiectomy
maintains leydig cell function, not fertility
basics of stage 1, 2, 3 in staging system
1 - no evidence of mets, 2 - retroperitoneal mets, 3 - chest mets or disseminated mets
physical exam potion of clinical staging - what lymph nodes are palpated
cervical and axillary
what kind of visceral metastasis does not = poor prognosis
pulmonary
lymphatic drainage based on gonadal vein drainage - Left
left GV drains to L renal vein –> lymphatic drainage to left peri-aortic area
lymphatic drainage based on gonadal vein drainage - right
right GV drains to IVC –> lymphatic drainage to inter-aorta-caval region
2 main things setting apart seminoma from non seminoma on followup
seminoma does not have teratoma and seminoma is radiosensitive
incidence of occult retroperitoneal mets in seminoma
20%
2 equivelant mgmt options for CS 1 seminoma
abdominal EBRT for occult mets vs observation
% CS 1 patients with sem vs non-sem who will relapse due to micromets during observation
15% for sem vs 30% for non-sem
mgmt of seminoma who recur on observation
chemo with BEP x 3 or EP x 4
% of seminoma who will need chemo on observation for mets
20%
dose of retroperitoneal radiation for CS 1 seminoma
20 gy
how long do you watch patients with seminoma on surveillance
5 yrs
2 RF for retroperitoneal spread in seminoma
rete testis invasion and tumor > 4 cm
dog leg radiation for seminoma
not done
newer mgmt option for CS1 seminoma
carboplatin to all patients. still investigational
rationale for carboplatin in all CS1 seminoma
- seminoma sensitive to carboplatin, 2. low morbidity, 3. and easy to administer
CS 2 seminoma substratification
> 5 cm (bulky) or < 5 cm (nonbulky)
location of mets and CS 2 seminoma
retroperitoneal only
non bulky cs2 seminoma treatment
radiation therapy (felt to be less morbid than chemo)
cure with radiation alone in nonbulky cs 2 seminoma
90%
mgmt of recurrence after radiation in nonbulky cs 2 seminoma
chemo
cure of radiation + chemo in nonbulky cs 2 seminoma
95-99%
bulky CS 2 sem mgmt
chemo - BEP x 3 (or EP x 4)
rationale for chemo in bulky CS 2 sem
high risk of occult micromets outside retroperitoneum with bulky disease. chemo is systemic
CS 3 sem mgmt
chemo - bep x 3 (or ep x 4)
cure rate with chemo in CS3 sem
95%
post chemo mass in seminoma - initial mgmt
observation with imaging as 85% chance of necrosis only
postchemo mass in pure sem- imaging?
do pet scan
pet scan agent for sem
FDG
role of PET scan in sem
can distinguish necrosis from active cancer (teratoma is not present in sem)
do we still resect post-chemo masses > 3 cm in pure sem
only if pet is positive
mgmt of + pet in sem
post chemo RPLND or high dose chemo
pet and NSGCT
not useful
why is pet useless in NSGCT
cant distinguish teratoma from necrosis. no teratoma in seminoma
postchemo mass in NSGCT - % necrosis
45%
postchemo mass in NSGCT - % teratoma
45%
postchemo mass in NSGCT - % active ca
10%
NSGCT CS1s mgmt
chemo
why chemo in CS1s NSGCT
ct scan negative and likly have disease beyond retroperitoneum
NSGCT - % with active cancer in cs1
30%
% relapse after RPLND in NSGCT
30%
NSGCT surveilance - % relapse
30%
3 benefits to RPLND in stage 1
- stage retroperitoneum, 2. 50-75% pts cured, 3. less chemo
2 probs with RPLND in stage 1
- 70% overtreated, 2. extra-retroperitoneal mets not treated and will need chemo
CS 1 s mgmt
systemic chemo
CS 1 s- why chemo
have systemic disease from persistently elevted markers and neg imaging
what sexual action is affected with non-nerve sparing rplnd
ejaculation only. orgasm and sensation are nl
ejaculation rate for full bilateral templace
0
ejaculation rate for modified nerve sparing
99%
left standard template
left peri-aortic region and left gonadal vein
right standard template
right peri-caval, interaortocaval and right gonadal
left modified template - medial border
interaortocaval LN above IMA
right modified template - medial border
left (contralateral) peri-aortic LN (above IMA)
why are modified templates based on IMA
below IMA can effect the nerves
chemo for NSGCT CS 1 at relapse
bep x 3 or ep x 4
% fertility after chemo
25-50%
cardiovascular side effect with chemo
7x OR + HTN
neuro side effect with chemo
numbness, tingling, reynauds
surveilance - pure seminoma recurrence mgmt vs nsgct recurrence mgmt
pure sem - chemo or rad and thats it, nsgct 30% who recur and get chemo will still need surgery
advantage of surveilance in CS 1 NSGCT
only those with spread will need treatment
disadvantage to surveilance in NSGCT
1/3 given chemo will need surgery when they recur
main reason to avoid chemo in nsgct
fertility, other reasons (nausea, immune status) less significant. also now evidece of late toxicity
CS 1 nonseminoma - primary chemo option
BEP x 2
pro/cons to chemo in CS1
good cure rate, however overtreatment in 70%
CS1 - % with micromets at rplnd who will relapse postop
30%
adjuvant chemo in rplnd in CS 1?
BEP x 2
problem with adjuvant chemo after primary rplnd in CS 1
only 30% will have micromets, 70% overtreated
CS 2 or 3 - initial mgmt in NSGCT
70% cured with chemo
% with residual mass in CS 2/3 nsgct
30%
mgmt of residual mass in post chemo stage 2/3 NSGCT
rplns because 55% have cancer or teratoma
retroperitoneal mass cutoff for RPLND vs primary chemo
> 5-6 cm treated with chemo because of high (50%)likelyhood of extra-retroperitoneal disease
< 5-6 cm retroperitoneal mass and surgery cure rate in CS 2
50-70% cured with surgery and can be primary treatment
each initial tx (chemo or rplnd) requires the other about x %
30%
postchemo rplnd template
always full bilateral template
postchemo rplnd for nonseminoma - mgmt if cancer is found
give 2 rounds adjuvant chemo
when does late relapse usually happen
2 yrs after initial sccessful mgmt
how does late relapse usu present
elevated afp
tx of late relapse
always surgery unless unresectable or multifocal disease
what is despiration surgery
rplnd with elevated markers post chemo
seminoma CS1s mgmt
radiation (20 gy to periaortic and ipsilateral iliac) or single agent carboplatin
what differentiates stage 1a from 1b in TNM for Sem and Non-Sem
1B is confined to testicle with LVI or tunica vaginalis involvement
mgmt of nsgct stage 2a with S1 vs S0
S1 gets chemo (BEP x 3 or EP x 4), S0 has option for RPLND, chemo (BEP x 3 or EP x 4), or surveillance if highly motivated
Most common presentation of testes ca.
localized seminoma
Most common age range at presentation
20-35 y.o.
Risk factors for testes cancer
Cryptorchidism
Family or personal hx of testes cancer
Intra-tubular germ cell neoplasia
Must perform orchiopexy before ____ to decrease testicular cancer rates
puberty
Seminomas often have ____ that produce bHCG
synctiotrophoblasts
Choriocarcinoma
VERY HIGH ____
Spreads via ____
Hemorrhagic ____ mets
v high bHCG
Hematogenous spread
hemorrhagic brain mets
____ tumors are chemo/rads resistant
Teratoma
____ tumors are most commonly in pre-pubertal children
Yolk Sac
Imaging study for testicular mass
scrotal u/s
Tumor markers should be followed up ____ s/p orchiectomy
4-5 weeks
Staging imaging
CT abd/pelvis
CXR (low risk) vs CT chest
Tumor confined to testes + epididymis w/o LVI
p___
pT1
Tumor confined to testes + epididymis w LVI OR tunica vaginalis invasion
p___
pT2
Tumor invading spermatic cord
p___
pT3
Tumor invading scrotum
p___
pT4
Nodal disease
only applies to RP nodes
N1 - ___ cm
N1 - <2cm
N2 - 2-5 cm
N3 - >5 cm
Seminoma with <3cm Tumor confined to testes + epididymis w/o LVI
p___
T1a
Seminoma with >3cm Tumor confined to testes + epididymis w/o LVI
p___
T1b
Seminoma confined to testes is always clinical stage ____
T1
T1a - pT1
T1b - pT2-4
Seminoma with RP nodal mets & S0-1 is clinical stage ___
T2
T2a - cN1
T2b - cN2
T2c - cN3
Seminoma with distant mets is clinical stage ___
T3
T3a - S1
T3b - S2
T3c - S3
Half life of AFP
5-7 days
AFP is NEVER elevated in ____
seminoma
Half life of bHCG
24-36h
Half life of LDH
24 hrs
Yolk sac has elevated ___ tumor marker
AFP
Seminoma - localized or with pulmonary mets
____ risk disease
Good
Seminoma with non-pulmonary mets
____ risk disease
Intermediate
Non-seminoma with S1 tumor markers
____ risk disease
Good
Non-seminoma with S2 tumor markers
____ risk disease
Intermediate
Non-seminoma with S3 tumor markers OR mediastinal primary OR non-pulmonary mets
____ risk disease
Poor
Right testes tumors spread to ____ LNs
inter-aortocaval
Left testes tumors spread to ____ LNs
Para-aortic
ITCGN ___% develop testes cancer
50
ITCGN Treatment
Surveillance
Orchiectomy (100% cure)
XRT (100% cure)
Chemo (66% cure)
Relapse rates for seminoma
Surveillance only - ___%
1 round of Carboplatin - ___%
Surveil - 14%
Chemo - 4%
Median time to relapse for seminoma s/p orchiectomy
1.5 years
Strongest risk factors for non-seminoma relapse
LVI
Embryonal tumors
Relapse rates for seminoma (without risk factors)
Surveillance only - ___%
BEP x1 - ___%
15%
1%
Relapse rates for seminoma (with risk factors)
Surveillance only - ___%
BEP x1 - ___%
40%
3%
Treatment if node + at time of primary RPLND
N1 - ____
N2 - ____
N3 - ____
N1 - surveillance
N2 - EPx2 or BEPx2
N3 - BEPx3 or EPx4
To preserve antegrade ejaculation after RPLND, spare ___ nerves
L1-L3 post-ganglionic sympathetic nerves
behind the IVC
Bleomycin adverse effects
pulmonary toxicity
Which stages of non-seminoma do you offer primary RPLND?
Stage IIA/B
- do not perform with elevated tumor markers*
- potential reduces chemo burden*
Which stages of seminoma can you offer RT?
Stage IIA/B - nodal positive disease, 2-5 cm
Must wait at least ____ s/p chemo to perform PET CT
6 weeks
Seminoma s/p chemo
Next step if no mass or <3cm mass - ____
Surveillance
Seminoma s/p chemo
Next step if >3cm mass - ____
PET CT
- Negative - surveillance
- Positive - resection
Seminoma s/p chemo
Next step if tumor growth or tumor marker elevation - ____
2nd line chemo
TIP/VeIP
Non-seminoma s/p chemo
Next step if no mass or <1cm mass with normal tumor markers - ____
Surveillance or RPLND
Non-seminoma s/p chemo
Next step if >1cm mass with normal tumor markers - ____
post-chemo RPLND
Non-seminoma s/p chemo
Next step if persistent elevated tumor markers - ____
2nd line chemo
TIP/VeIP
Long term risks of chemo for testes ca patients
Cardiovascular disease
2ndary cancers
Management of post-chemo distant mets
resect if possible
Offer all patient ____ prior to treatment to maintain fertility
sperm banking
Treatment after trans-scrotal orchiectomy
Observe vs excise scar vs RT
pTX
Primary tumour can not be assessed
pT0
No evidence of primary tumour
pTIS
Intratubular germ cell neoplasia (carcinoma in situ)
pT1
Tumour limited to testis and epididymis without vascular/lymphatic invasion. Tumour may invade tunica albuginea but not tunica vaginalis
pT2
Tumour limited to testis and epididymis with vascular/lymphatic invasion, or tumour extending through tunica albuginea with involvement of tunica vaginalis
pT3
Tumour invades spermatic cord with or without vascular/lymphatic invasion
pT4
Tumour invades scrotum with or without vascular/lymphatic invasion
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis with a lymp node mass 2 cm or less in greatest dimension or multiple lymph nodes, none more than 2 cm in greatest dimension
N2
Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or more than 5 nodes positive, none more than 5 cm; or evidence of extranodal extension of tumour
N3
Metastasis with a lymph node mass more than 5 cm in greatest dimension
MX
Distant metastasis cannot be assessed
M0
No distant metastasis
M1
Distant metastasis
M1a
Non-regional lymph node(s) or lung metastasis
M1b
Distant metastasis other than non-regional lymph nodes and lung metastasis
SX
Serum marker studies not available or not performed
S0
Serum marker study levels within normal limits
S1
LDH <1,5xN and hCG < 5 000 and AFP < 1 000
S2
LDH 1,5-10xN or hCG 5 000-50 000 or AFP 1 000-10 000
S3
LDH >10xN or hCG >50 000 or AFP >10 000
following adult male germ cell tumor (GCT) subtypes arise from germ cell neoplasia in situ (GCNIS)
a. embryonal tumor. b. choriocarcinoma. c. classic seminoma. e. teratoma.
