Editing Germ Cell Tumours (section)

==== <span style="color:#ff0000">Tumour markers </span><span style="color:#0000ff">(A YET, B SEC)</span> ====

===== <span style="color:#0000ff">A</span><span style="color:#ff0000">FP</span> =====
* At diagnosis, elevated in 50-70% of low-stage (CS I, IIA, and IIB) NSGCT and 60-80% of advanced (CS IIC and III) NSGCT
* '''<span style="color:#ff0000">Produced by (3):</span>'''
*# '''<span style="color:#0000ff">Y</span><span style="color:#ff0000">olk sac</span>'''
*# '''<span style="color:#0000ff">E</span><span style="color:#ff0000">C</span>'''
*# '''<span style="color:#0000ff">T</span><span style="color:#ff0000">eratoma</span>'''
** '''<span style="color:#ff0000">Choriocarcinomas and seminomas do not produce AFP</span>'''
*** '''<span style="color:#ff0000">Clinical implication: pure seminoma in the primary tumor with an elevated serum AFP should be treated as NSGCT</span>'''
* '''Upper limit < 11 ng/mL'''
** Despite most laboratories considering AFP > 8ng/mL to be abnormally elevated, a proportion of the population may have levels up to 15-25 ng/mL in the absence of any pathology; '''treatment decisions based solely on “elevated” AFP levels that are stable and <25 ng/mL is discouraged'''
* '''<span style="color:#ff0000">Serum half-life: 5-7 days</span>'''
* '''Other causes of elevated AFP:'''
*# '''Non-malignant liver disease (infectious, drug-induced, alcohol-induced, autoimmune)'''
*# '''Hepatocellular carcinoma'''
*# Cancers of the stomach, pancreas, biliary tract, and lung
*# Ataxic telangiectasia
*# Hereditary tyrosinemia
*# Hereditary persistence of AFP (a congenital alteration in the hepatic nuclear factor binding site of the AFP gene)

===== <span style="color:#0000ff">β</span>-hCG =====
* At diagnosis, elevated in 20-40% of low-stage NSGCT and 40-60% of advanced NSGCT
* '''<span style="color:#ff0000">Produced by (3):</span>'''
*# '''<span style="color:#0000ff">S</span><span style="color:#ff0000">eminoma (15% of cases)</span>'''
*# '''<span style="color:#0000ff">E</span><span style="color:#ff0000">C</span>'''
*# '''<span style="color:#0000ff">C</span><span style="color:#ff0000">horiocarcinoma</span>'''
* '''Upper limit: <5 mU/mL'''
**'''<span style="color:#ff0000">Levels > 10,000 IU/L are usually associated with choriocarcinoma.</span>'''
* '''<span style="color:#ff0000">Serum half-life: 24 to 36 hours</span>''' (2019 AUA Update Peds Testis Tumours says 24-48 hours)
* '''<span style="color:#ff0000">Other causes of elevated hCG:</span>'''
*# '''<span style="color:#ff0000">Hypogonadism</span>'''
*#* '''<span style="color:#ff0000">LH will be elevated and can be a cause false-positive elevated hCC due to cross-reactivity of the hCG assay with LH</span>'''
*#** '''<span style="color:#ff0000">Supplemental testosterone decreases LH levels, allowing accurate assessment of hCG levels thereafter[https://pubmed.ncbi.nlm.nih.gov/88528/]</span>'''
*# '''Cancers of the liver, biliary tract, pancreas, stomach, lung, breast, kidney, and bladder.'''
*#* The α subunit of hCG is common to several pituitary tumors, and so immunoassays for hCG are directed at the β subunit.
*# '''Cannabis use'''

===== <span style="color:#ff0000">LDH</span> =====
* At diagnosis, elevated in ≈20% of low-stage GCT and 20-60% of advanced GCT
* '''Least relevant and clinically applicable of the tumour markers'''
** Non-specific marker
** '''Main use in GCT is in the''' '''prognostic (S stage classification) assessment at diagnosis.'''
** '''Treatment decisions based solely on LDH elevation in the setting of normal AFP and hCG should be discouraged.'''
* '''Normal value 48-115 IU/liter'''
**Magnitude of LDH elevation correlates with bulk of disease.
* '''<span style="color:#ff0000">Serum half-life: varies[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818947/]</span>'''
* LDH is expressed in smooth, cardiac, and skeletal muscles and can be elevated from cancerous (kidney, lymphoma, GI, breast) or non-cancerous conditions (heart failure, anemia, HIV)

===== <span style="color:#ff0000">Pre-orchiectomy tumour markers</span> =====
* '''<span style="color:#ff0000">Uses (2):</span>'''
*# '''<span style="color:#ff0000">Support initial diagnosis</span>'''
*#* '''<span style="color:#ff0000">Should not be used to guide decision making about whether or not to perform a radical orchiectomy''' because AFP or hCG levels in the normal range do not rule out GCT.
*# '''<span style="color:#ff0000">Interpret tumor marker levels after orchiectomy.</span>'''
*#* '''Essential to know whether persistently elevated post-orchiectomy tumour markers are declining compared to pre-orchiectomy levels by their respective half-lives or not, or whether they are rising, as this impacts subsequent treatment decisions.'''
* '''Should not be used for clinical staging and risk stratification'''
** Can lead to over- or under-treatment with resulting excess rates of toxicity or relapse, respectively.

===== <span style="color:#ff0000">Post-orchiectomy tumour markers</span> =====
* '''<span style="color:#ff0000">Uses (2):</span>'''
*# '''<span style="color:#ff0000">Evaluate for metastases in the case of persistently elevated/rising post-orchiectomy tumour markers</span>'''
*#* Tumour marker levels should normalize after 4 half-lives[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818947]
*#**Serum AFP levels should return to normal levels 20–28 days after effective therapy.
*#*If borderline elevated (within 3x upper limit of normal) post-orchiectomy markers (AFP and hCG), confirm a rising trend before management decisions are made as false-positive elevations may occur.
*# '''<span style="color:#ff0000">Evaluate for recurrence during surveillance and after completion of therapy (chemotherapy, radiation, surgery).</span>'''