Testicular Cancer Flashcards
Presentation
IF localized –> nodule, painless mass, dull ache or heavy sensation (30%), gynecomastia, testicular atrophy, infertility
*Sometime testis is just enlarged and indurated, and you don’t necessarily feel a mass
Lower abdominal pain
Tumor markers to test for as part of initial workup
bHCG + AFP + LDH
Term for premalingant condition associated with testicular cancer
Germ-cell neoplasia in situ (GCNIS)
Primary distinction between germ cell tumors
Seminoma histologies
Nonseminomatous histologies
nonseminomatous histologies
Embryonal cell
Choriocarcinoma
Yolk sac
Teratoma
Stroma tumors (sertoli, leydig)
biomarker associated with yolk sac histology
AFP
biomarker associated with choriocarcinoma + level typically
beta-HCG
*Extremely high levels
most aggressive subtype
choriocarcinoma
Serum tumor markers used in testicular cancer
LDH
AFP
beta-HCG
Chemo regimens used for testicular cancer
EP
BEP
VIP
TIP
what is EP regimen
etoposide/cisplatin
what is BEP regimen
belomycin/etoposide/cisplatin
Stage IIB/C seminoma management (RP lymphadenopathy)
Inguinal orchiectomy + chemo (regimen determined based off risk level)
response assessment
tumor markers + CT-abdomen pelvis
surveillance
Tumor markers, CXR, CT abdomen/pelvis
Seminoma origin
Originates in the germinal epithelium of the seminiferous tubules. Thus tumor originates in the testes. These are slow growing and more indolent and curable than nonseminomatous.
5 year survival of testicular cancer
Over 95 percent. Testicular cancers are among the most curable solid neoplasms; the five-year survival rate is
Pathway of treatment (surgery vs. chemo)
For men who present with clinically advanced disease, we perform a radical orchiectomy prior to chemotherapy whenever possible. Despite this, there are some men who present with life-threatening advanced disease who undergo systemic chemotherapy prior to orchiectomy (“delayed orchiectomy”).
meaning of “germ cell tumor”
tumor arising from germ cell, so either testicular or ovarian
Primary class of chemo used for testicular
platinum-based chemotherapy
High risk features of NSGCT
1) LVI
2) Predominance of an embryonal carcinoma component
3) T3/ T4
*Rework question
RPLND means
retroperitoneal lymph node dissection
Difference in management between seminomatous and nonseminomatous testicular cancer
Only differs for localized. For men with advanced testicular germ cell tumors (GCTs), management is the same
how management of advanced testicular tumor is determined
risk stratification
most sensitive means for detecting relapse in men with NSGCT
Tumor markers
Management differences in advanced NSGCT in general
Different number of cycles of BEP
Pure seminoma biomarkers
AFP normal
bHCG can be elevated
LDH can be elevated
Stage IIA NSGCT management after radical orchiectomy IF markers negative
Nerve sparing RPLND or primary chemo with BEP
term for testicle removal surgery
radical inguinal orchiectomy
What are the most common histologies w/ testicular cancer in order for prevalence
- most commonly seminoma
- Embryonal cell and yolk sac equally distributed
- choriocarcinoma very rare.
What are the stages?
Stages I, II, and III (there is no stage IV)
Stage II means
1) Retroperitoneal lymph node involvement
2) STMs can only be mildly elevated
Stage III means
Lymphadenopathy anywhere else other than retroperitoneal
RF’s
- Cryptorchidism (Undescended) (prepubertal orchidectomy decreases risk of testicular cancer)
- Infertility
- FH of testis cancer
Genetic fingerprint of germ cell tumors
Isochromosome 12p
*Testis GCTs invariably have increased copies of genetic material from 12p
What are the germ cell tumors
Seminoma
Embryonal carcinoma
Choriocarcinoma
Yolk sac tumor
Teratoma
Spermatocytic tumor
What are the sex cord/gonadal stroll tumors?
- Leydig cell tumor
- Sertoli cell tumor
- Granulosa cell tumor
Benign causes of AFP elevation
Liver disease, toxicity
AFP half-life + clinical relevance of half-life
1 week
*So if not falling by 50% following orchiectomy, this may indicate residual cancer
Upper limit of normal for AFP + clinical relevance
20
*Ignore slightly elevated AFP, very nonspecific. Pay more attention to the pattern.
beta-hCG produced by which tumors?
All GCT’s, but extremely elevated in choriocarcinoma
beta-hCG half life
Less than 3 days
False positives for beta-hCG
- Reports that marijuana consumption leads to elevated HCG
Utility of LDH
- prognostic/staging of disseminated nonseminomas
- Not used to monitor response to treatment
Risk determined by
- Tumor marker levels
AFP level indicating good, intermediate, and poor risk
Good = less than 1000
Intermediate = 1000-10,000
Poor = Greater than 10k
B-hCG level indicating good, intermediate, and poor risk
Good = less than 5000
Intermediate = 5000-50,000
Poor = Greater than 50k
LDH level indicating good, intermediate, and poor risk
Good = less than 1.5x ULN
Intermediate = 1.5-10x ULN
Poor = Greater than 10x ULN
When sperm banking is needed
- prior to chemo/RT, *doesn’t need to happen before orchiectomy
Primary determinant of risk of relapse
Lymphovascular invasion
What is Stage 1S
- No radiographic evidence of tumor spread but tumor markers stay elevated after orchiectomy
Treatment of Stage 1S
Same as stage III, assume metastatic
Tumors in which Stage 1S occurs
nonseminoma
Stage I seminoma treatment
*Individualized, patient preference but surveillance is guideline preferred
*Surveillance
Vs
Single agent carboplatin (1 or 2 doses)
Vs
RT to retroperitoneum (fallen out of favor due to increased risk of secondary cancer – why do this if you can cure primary?)
Management of Stage II seminoma
RT or chemo (BEPx3 or EPx4)
IF bulky RP disease –> chemo preferred
Stage I NSGCT management
Surveillance (preferred)
OR
RPLND
OR
BEP x 1
Surveillance schedule
- intense
- monthly visits required for tumor markers
Stage II NSGCT management
IIA: RPLND or BEP
IIB/C or IIA w/ SI: BEP x3 or EPx4
Caveat about RPLND with Stage II
- you may not necessarily avoid chemo (if nodes are malignant, will need chemo)
What is VIP?
- etoposide (VePesid)
- ifosfamide
- cisplatin
- meson
2nd line chemo regimens
TIP
VeIP
High dose carboplatin and etoposide
Bleomycin pneumonitis presentation
Dry cough, rales, dyspnea,
What are bleomycin precautions?
1) Avoiding high partial pressure O2 in hospital or during surgery
2) Minimizing intraoperative IV fluids
CXR caveat to know of with bleomycin
- can cause pseudonodules (inflammatory nodules that are benign)
Primary cisplatin toxicities
- renal toxicity
- ototoxicity
- peripheral neuropathy
When EP is used instead of BEP
- Elderly
- poor renal function
- lung disease
- serious athlete (lung function)
Chemo for good-risk disease
BEPx3
Chemo for intermediate or poor risk disease
BEPx4
Criteria for intermediate/poor risk disease
- AFP greater than 1000
- B-hCG greater than 5K
- LDH greater than 1.5x ULN
- mets to organs other than the lungs
- mediastinal primary NSGCT
What is TIP?
Taxol
Ifosfamide
Cisplatin
Second line systemic therapy options
VeIP x4
OR
TIP x 4
OR
HDCT x 2
Growing teratoma concept
Masses that are growing during chemo are often teratoma. Need surgery.
*Tumor markers will go down
*Rare but commonly tested
Management of seminoma with residual mass
Surveillance (most are benign)
IF greater than 3cm – get PET/CT
Management of NSGCT with residual mass after completion of chemotherapy
Surgical resection
***never observation
**No role for PET/CT unless pure seminoma
Carboplatin vs cisplatin efficacy for NSGCT’s
Carboplatin is less effective
In research, why do testicular cancer patients do better at high volume institutions?
***Patients get more chemotherapy and it is on time. Fewer dose reductions. You shouldn’t dose reduce in cancer being treated with curative intent (for low counts or mild AKIs).
Teratoma PET avidity
Teratomas don’t light up on PET
Management of NSGCT patient with extensive lung mets
- Brain MRI (patients with extensive lung mets are at higher risk for brain mets)
Management of bleomycin lung toxicity? Rechallenge?
- stop the drug, switch to EP (drop bleomycin)
- never rechallenge (pulmonary fibrosis can be fatal)
- high dose steroids
presentation of bleomycin pulmonary toxicity
- can start off as penumonitis, but can progress to fibrosis
Significance of rising tumor markers at the end of treatment
chemorefractory disease
chemo in locally advanced testicular cancer is followed by
RPLND
Why RPLND is done at the end of treatment with GCTs
(teratoma will need to be resected because it is not chemo sensitive)
what is growing teratoma syndrome?
- residual mass (typically RP) increasing in size despite normalized or decreasing tumor marker levels
Presentation of leydig cell tumor
- gynecomastia, impotence, loss of libido
Paraneoplastic phenomena of testicular cancer
- hyperthyroidism (TSH and hCG have a common alpha subunit
- limbic encephalitis (anti-Ma2 antibodies
How is staging done in testicular cancer
radical inguinal orchiectomy (imaging is not reliable)
Relationship between microlithiasis and testicular cancer
- strong association but not causal
Problem with CT abdomen for staging
High false negative rates in retroperitoneum w/ occult micrometastases (ie not sensitive for disease in the retroperitoneum)
Where relapse typically occurs
Retroperitoneal lymph nodes
Tumor markers in pure seminomas
- AFP never elevated (seminomas don’t produce AFP)
- BetaHCG typically normal but can be elevated in 20%
Precursor lesion to testicular cancer
Testicular germ cell neoplasia in situ (GCNIS
TNM staging components for NSGCT’s
TNM + S (tumor markers)
N3 disease
lymph node mass larger than 5 cm in greatest dimension
N2 disease
lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension
N1 disease
lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive
T4 disease
Tumor invades scrotum
T3 disease
Tumor directly invades spermatic cord soft tissue
T2 disease
Lymphovascular invasion OR Tumor invading hilar soft tissue or epididymis or penetrating visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion
Prognostic/risk stratification model used in testicular cancer
International Germ Cell Cancer Collaborative Group (IGCCCG)
Risk groups for NSGCTs in IGCCCG model
good-, intermediate-, and poor-risk
What is Stage 1S disease?
NSGCT limited to the testis on clinical staging but who have persistent elevation of tumor markers
Relevance of spermatocytic features on path
Presence virtually eliminates the chance of recurrence. Positive prognosticator.
Dominant pathology of testicular cancer in older men
LYMPHOMA
Clinical features of embryonal cell histology
- Higher risk of relapse.
- early progression and development of metastatic disease
Microscopic findings with embryonal cell
hemorrhage or necrosis within the tumor
which testicular cancers produce AFP?
- yolk sac very high
- embryonal but less so than yolk sac
- pure choriocarcinoma and pure seminoma do not produce AFP
why do you never biopsy testicular?
Seeding of biopsy track
Backbone of chemotherapy in testicular cancer
Etoposide, cisplatin
Primary long term toxicities of chemotherapy in testicular
SMNs + CV disease
Meaning of SMNs
secondary malignant neoplasms
Why surgery/RPLND is never done in seminoma post chemotherapy
Desmoplastic reaction
Does primary site affect outcome in seminoma?
NO
Second line for advanced NSGCT
Conventional-dose chemotherapy (CDCT) w/ TIP for 4 cycles (or VeIP for 4 cycles)
High-dose chemo (HDCT) w/ sequential (2-3) ASCT
Intermediate risk NSGCT per IGCCCG
ALL OF THE FOLLOWING
Testicular or retroperitoneal primary tumors
No metastases to organs other than the lungs and/or lymph nodes
Serum AFP 1000 to 10,000 ng/mL* or
Serum beta-hCG 5000 to 50,000 milli-international units/mL* or
LDH 3 to 10 times the upper limit of normal*
Poor risk NSGCT per IGCCCG
Any of the following:
Mediastinal primary with or without metastases
Metastases to organs other than the lungs and/or lymph nodes
Serum AFP >10,000 ng/mL*
Serum beta-hCG >50,000 milli-international units/mL*
LDH more than 10 times the upper limit of normal*
Good risk NSGCT per IGCCCG
All of the following:
Testicular or retroperitoneal primary tumors
No metastases to organs other than the lungs and/or lymph nodes
Serum AFP <1000 ng/mL, beta-hCG <5000 milli-international units/mL, and LDH <3 times the upper limit of normal*
