Germ Cell Tumours: Difference between revisions
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** US 2021: 440[https://seer.cancer.gov/statfacts/html/testis.html] | ** US 2021: 440[https://seer.cancer.gov/statfacts/html/testis.html] | ||
*** 5-year relative survival: 94.9% (compared to prostate 97.5%, bladder 77.1%, and kidney/renal pelvis 75.6%)[https://seer.cancer.gov/statfacts/html/testis.html] | *** 5-year relative survival: 94.9% (compared to prostate 97.5%, bladder 77.1%, and kidney/renal pelvis 75.6%)[https://seer.cancer.gov/statfacts/html/testis.html] | ||
== Risk | == Risk Factors == | ||
* '''<span style="color:#ff0000"> | * '''<span style="color:#ff0000">Inherited (3):</span>''' | ||
*# '''<span style="color:#ff0000">Family history of GCT</span>''' | *# '''<span style="color:#ff0000">Family history of GCT</span>''' | ||
*# '''<span style="color:#ff0000">Germ Cell Neoplasia In-Situ (GCNIS)</span>''' | |||
*# '''<span style="color:#ff0000">Germ Cell Neoplasia In-Situ (GCNIS)</span> | *#* Previously referred to as intratubular germ cell neoplasia (ITGCN) unclassified | ||
*#* '''All adult invasive GCTs arise from GCNIS, except spermatocytic seminoma.''' | *#*'''All adult invasive GCTs arise from GCNIS, except spermatocytic seminoma.''' | ||
*#* Among males with GCNIS, the risk of developing invasive GCT is ≈50% at 5 years | *#* Among males with GCNIS, the risk of developing invasive GCT is ≈50% at 5 years | ||
*#* '''GCNIS develops before birth from an arrested gonocyte''' | *#* '''GCNIS develops before birth from an arrested gonocyte''' | ||
*# '''<span style="color:#ff0000">Race</span>''' | *# '''<span style="color:#ff0000">Race</span>''' | ||
*#* '''Caucasian risk > African-American''' | *#* '''Caucasian risk > African-American''' | ||
*'''<span style="color:#ff0000">Acquired (2):</span>''' | |||
*#'''<span style="color:#ff0000">Cryptorchidism</span>''' | |||
*#* '''Ipsilateral testis: relative risk 4-6x; relative risk decreases to 2-3x if orchidopexy is performed before puberty''' | |||
*#* '''Contralateral testis: slightly increased risk''' (relative risk 1.74x) | |||
*#'''<span style="color:#ff0000">Personal history of GCT</span>''' | |||
== Genetics == | == Genetics == | ||
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* '''<span style="color:#ff0000">Signs and Symptoms</span>''' | * '''<span style="color:#ff0000">Signs and Symptoms</span>''' | ||
**'''<span style="color:#ff0000">Most common presentation of testicular cancer: painless scrotal mass</span>''' | **'''<span style="color:#ff0000">Most common presentation of testicular cancer: painless scrotal mass</span>''' | ||
**Symptoms related to metastatic disease are the presenting complaint in 10-20% of patients | **'''Symptoms related to metastatic disease (e.g. shortness of breath)''' are the presenting complaint in 10-20% of patients | ||
==== Physical exam ==== | ==== Physical exam ==== | ||
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* '''Normal value 48-115 IU/liter''' | * '''Normal value 48-115 IU/liter''' | ||
**Magnitude of LDH elevation correlates with bulk of disease. | **Magnitude of LDH elevation correlates with bulk of disease. | ||
* '''<span style="color:#ff0000">Serum half-life: | * '''<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) | * 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) | ||
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* '''<span style="color:#ff0000">Uses (2):</span>''' | * '''<span style="color:#ff0000">Uses (2):</span>''' | ||
*# '''<span style="color:#ff0000">Support initial diagnosis</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''' | *#* '''<span style="color:#ff0000">Should not be used to guide decision making about whether or not to perform a radical orchiectomy''' | ||
*# '''<span style="color:#ff0000">Interpret tumor marker levels after orchiectomy | *#** 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.''' | *#* '''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''' | * '''Should not be used for clinical staging and risk stratification''' | ||
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* '''<span style="color:#ff0000">Uses (2):</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>''' | *# '''<span style="color:#ff0000">Evaluate for metastases in the case of persistently elevated/rising post-orchiectomy tumour markers</span>''' | ||
*#* 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. | *#* 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>''' | *# '''<span style="color:#ff0000">Evaluate for recurrence during surveillance and after completion of therapy (chemotherapy, radiation, surgery).</span>''' | ||
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* '''Imaging findings''' | * '''Imaging findings''' | ||
** '''Typical GCT is hypoechoic''' | ** '''Typical GCT is hypoechoic''' | ||
** 2 or more discrete lesions may be identified | ** 2 or more discrete lesions may be identified[[File:Ultrasound images of seminomas.jpg|none|thumb|493x493px|Source: [[commons:File:Ultrasound_images_of_seminomas.jpg|Wikipedia]] (a) Seminoma usually presents as a homogeneous hypoechoic nodule confined within the tunica albuginea. (b) Sonography shows a large heterogeneous mass occupying nearly the whole testis but still confined within the tunica albuginea, it is rare for seminoma to invade to peritesticular structures.]][[File:Ultrasonography of embryonal cell carcinoma.jpg|none|thumb|Embryonal cell carcinoma. Longitudinal ultrasound image of the testis shows an irregular heterogeneous mass that forms an irregular margin with the tunica albuginea. Source: [[wikipedia:Scrotal_ultrasound#/media/File:Ultrasonography_of_embryonal_cell_carcinoma.jpg|Wikipedia]]]] | ||
** '''<span style="color:#ff0000">Testicular microlithiasis</span>''' | ** '''<span style="color:#ff0000">Testicular microlithiasis</span>''' | ||
*** '''Unclear significance''' '''in the general population''' | *** '''Unclear significance''' '''in the general population''' | ||
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**** '''<span style="color:#ff0000">No further evaluation or screening in incidentally detected microlithiasis</span>''' | **** '''<span style="color:#ff0000">No further evaluation or screening in incidentally detected microlithiasis</span>''' | ||
**** '''<span style="color:#ff0000">If established risk factor and testicular microlithiasis, counsel patient about the potential increased risk of GCT, need for periodic self-examination and follow-up with a medical professional</span>''' | **** '''<span style="color:#ff0000">If established risk factor and testicular microlithiasis, counsel patient about the potential increased risk of GCT, need for periodic self-examination and follow-up with a medical professional</span>''' | ||
[[File:Testicular microlithiasis 131206091733625.gif|thumb|Testicular microlithiasis in a patient with contralateral orchiectomy due to testicular malignancy. Echogenic foci viewed in testis as small white spots. Source: [[commons:File:Testicular_microlithiasis_131206091733625.gif|Wikipedia]]|center]] | |||
===== MRI ===== | ===== MRI ===== | ||
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** '''<span style="color:#ff0000">"Borderline" retroperitoneal lymph nodes</span>''' | ** '''<span style="color:#ff0000">"Borderline" retroperitoneal lymph nodes</span>''' | ||
*** '''<span style="color:#ff0000">Lymph nodes 5-9 mm in the primary landing zone should be viewed with suspicion for regional lymph node metastasis,</span> particularly if they are anterior to the great vessels''' | *** '''<span style="color:#ff0000">Lymph nodes 5-9 mm in the primary landing zone should be viewed with suspicion for regional lymph node metastasis,</span> particularly if they are anterior to the great vessels''' | ||
** Limitations | ** '''Limitations''' | ||
*** Understaging | *** '''Understaging''' | ||
**** 25-35% of patients with CSI NSGCT and a “normal” CT scan will be found to have pathologically involved retroperitoneal lymph nodes at RPLND | **** 25-35% of patients with CSI NSGCT and a “normal” CT scan will be found to have pathologically involved retroperitoneal lymph nodes at RPLND | ||
*** Overstaging | *** '''Overstaging''' | ||
**** 12-40% of patients with CS IIA and IIB disease will be found to have pathologically negative lymph nodes at RPLND | **** 12-40% of patients with CS IIA and IIB disease will be found to have pathologically negative lymph nodes at RPLND | ||
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*** '''<span style="color:#ff0000">Necessary to complete staging in patients with confirmed GCTs</span>''' | *** '''<span style="color:#ff0000">Necessary to complete staging in patients with confirmed GCTs</span>''' | ||
*** '''<span style="color:#ff0000">Should not delay orchiectomy</span>''' | *** '''<span style="color:#ff0000">Should not delay orchiectomy</span>''' | ||
** '''Modality: plain-film chest x-ray vs. CT''' | ** '''<span style="color:#ff0000">Modality: plain-film chest x-ray vs. CT</span>''' | ||
*** '''Chest x-ray''' | *** '''<span style="color:#ff0000">Chest x-ray</span>''' | ||
**** '''Indications''' | **** '''<span style="color:#ff0000">Indications</span>[https://pubmed.ncbi.nlm.nih.gov/31059667/ ★]''' | ||
***** '''Suspected clinical stage I seminoma'''; preferred over CT | ***** '''<span style="color:#ff0000">Suspected clinical stage I seminoma</span>'''; preferred over CT | ||
****** '''When tumor markers are normal, the rate of skip metastasis to the thorax in seminoma is close to 0%,''' and the addition of CT chest to chest x-ray is very unlikely to alter treatment decisions. | ****** '''When tumor markers are normal, the rate of skip metastasis to the thorax in seminoma is close to 0%,''' and the addition of CT chest to chest x-ray is very unlikely to alter treatment decisions. | ||
*** '''CT scan''' | *** '''<span style="color:#ff0000">CT scan</span>''' | ||
**** '''Indications (3)''' | **** '''<span style="color:#ff0000">Indications (3)</span>[https://pubmed.ncbi.nlm.nih.gov/31059667/ ★]''' | ||
****# '''NSGCT''' | ****# '''<span style="color:#ff0000">NSGCT</span>''' | ||
****#* '''Skip metastases are more common in non-seminoma than seminoma.''' | ****#* '''Skip metastases are more common in non-seminoma than seminoma.''' | ||
****# '''Elevated and rising post-orchiectomy markers (hCG and AFP)''' | ****# '''<span style="color:#ff0000">Elevated and rising post-orchiectomy markers (hCG and AFP)</span>''' | ||
****# '''Any evidence of metastases on abdominal/pelvic imaging, chest x-ray or physical exam.''' | ****# '''<span style="color:#ff0000">Any evidence of metastases on abdominal/pelvic imaging, chest x-ray or physical exam.</span>''' | ||
* '''Other''' | * '''Other''' | ||
** '''Bone scan and CT brain''' | ** '''Bone scan and CT brain''' | ||
***'''No role for routine bone scintigraphy or brain CT imaging at the time of diagnosis.''' | ***'''No role for routine bone scintigraphy or brain CT imaging at the time of diagnosis.[https://pubmed.ncbi.nlm.nih.gov/31059667/ ★]''' | ||
**** In the absence of symptoms or other clinical indicators of disease, visceral metastasis to bone and brain is uncommon in GCT | **** In the absence of symptoms or other clinical indicators of disease, visceral metastasis to bone and brain is uncommon in GCT | ||
**** '''Indications for bone scan and CT brain (3):''' | **** '''Indications for bone scan and CT brain (3):''' | ||
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* '''pT0''': no evidence of primary tumour | * '''pT0''': no evidence of primary tumour | ||
* '''pTis''': germ cell neoplasia in situ | * '''pTis''': germ cell neoplasia in situ | ||
* '''<span style="color:#ff0000">pT1: tumour limited to testis (including rete testis invastion) without | * '''<span style="color:#ff0000">pT1: tumour limited to testis (including rete testis invastion) without lymphovascular invasion (LVI)</span>''' | ||
** '''<span style="color:#ff0000">For pure seminoma:</span>''' | ** '''<span style="color:#ff0000">For pure seminoma:</span>''' | ||
*** '''<span style="color:#ff0000">pT1a: tumour size < 3 cm</span>''' | *** '''<span style="color:#ff0000">pT1a: tumour size < 3 cm</span>''' | ||
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===== Special scenarios ===== | ===== Special scenarios ===== | ||
====== Residual masses after chemotherapy for seminoma ====== | ====== Residual masses after chemotherapy for seminoma ====== | ||
* '''After first-line chemotherapy, 60-80% of patients have radiologically detectable residual masses.''' | |||
* After first-line chemotherapy, 60-80% of patients have radiologically detectable residual masses. | |||
* '''<span style="color:#ff0000">Histology of residual masses:</span>''' | * '''<span style="color:#ff0000">Histology of residual masses:</span>''' | ||
** '''<span style="color:#ff0000">Necrosis 90%</span>''' | ** '''<span style="color:#ff0000">Necrosis 90%</span>''' | ||
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** '''<span style="color:#ff0000">If residual masses< 3 cm: observation.</span>''' | ** '''<span style="color:#ff0000">If residual masses< 3 cm: observation.</span>''' | ||
** Post-chemotherapy radiotherapy has no role in the management of residual masses | ** Post-chemotherapy radiotherapy has no role in the management of residual masses | ||
====== Residual masses after radiotherapy for seminoma ====== | |||
* '''Patients should undergo biopsy and histologic confirmation of the suspected lesion before management decisions are made.''' | |||
** '''Although rare, seminoma may transform into NSGCT elements, and this should be considered in patients with metastatic seminoma who fail to respond to conventional therapy.''' | |||
** Either an open or a robotic/laparoscopic biopsy of the para-aortic mass is an acceptable approach if CT-guided biopsy is not feasible or the result is non-diagnostic. | |||
** RPLND should not be performed without histologic confirmation of NSGCT pathology. | |||
====== Relapse of seminoma ====== | ====== Relapse of seminoma ====== | ||
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** '''Guidelines''': | ** '''Guidelines''': | ||
*** '''2010 CUA Consensus Statement: surveillance preferred for all CSI NSGCT''' | *** '''2010 CUA Consensus Statement: surveillance preferred for all CSI NSGCT''' | ||
*** '''2019 AUA Guidelines:''' | *** '''<span style="color:#ff0000">2019 AUA Guidelines:</span>''' | ||
**** '''CSIA NSGCT: surveillance recommended''' | **** '''<span style="color:#ff0000">CSIA NSGCT: surveillance recommended</span>''' | ||
**** '''CSIB NSGCT: all options are recommended''' | **** '''<span style="color:#ff0000">CSIB NSGCT: all options are recommended</span>''' | ||
**** '''<span style="color:#ff0000">RPLND is recommended if there is any secondary somatic malignancy (e.g. rhabdomyosarcoma, adenocarcinoma, or primitive neuroectodermal tumor) in the primary tumor</span>''' | **** '''<span style="color:#ff0000">RPLND is recommended if there is any secondary somatic malignancy (e.g. rhabdomyosarcoma, adenocarcinoma, or primitive neuroectodermal tumor) in the primary tumor</span>''' | ||
* '''<span style="color:#ff0000">Surveillance for clinical stage I NSGCT</span>''' | * '''<span style="color:#ff0000">Surveillance for clinical stage I NSGCT</span>''' | ||
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** '''Chemotherapy''' | ** '''Chemotherapy''' | ||
*** '''Cisplatin is associated with fatigue, myelosuppression, infection, peripheral neuropathy, hearing loss, diminished renal function, and death.''' | *** '''Cisplatin is associated with fatigue, myelosuppression, infection, peripheral neuropathy, hearing loss, diminished renal function, and death.''' | ||
***'''Etoposide is associated with myelosuppression''' | |||
** '''Radiation''' | ** '''Radiation''' | ||
*** '''Associated fatigue, nausea and vomiting, leukopenia, and dyspepsia''' | *** '''Associated fatigue, nausea and vomiting, leukopenia, and dyspepsia''' | ||
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*** Risk increased with either subdiaphragmatic radiation or platinum-based chemotherapy | *** Risk increased with either subdiaphragmatic radiation or platinum-based chemotherapy | ||
*** Patients should establish regular care with a primary care physician for appropriate health care maintenance and cancer screening as appropriate. | *** Patients should establish regular care with a primary care physician for appropriate health care maintenance and cancer screening as appropriate. | ||
** '''Chemotherapy specific''' | ** '''<span style="color:#ff0000">Chemotherapy specific''' | ||
*** '''Bleomycin | *** '''<span style="color:#ff0000">Bleomycin''' | ||
*** '''Cisplatin | ****'''<span style="color:#ff0000">Pulmonary complications (including pulmonary fibrosis)''' | ||
*** ''' | ****'''<span style="color:#ff0000">Raynaud phenomenon''' | ||
****'''Mild myelosuppressive effects at high doses.''' | |||
*** '''<span style="color:#ff0000">Cisplatin''' | |||
****'''<span style="color:#ff0000">Nephrotoxicity''' | |||
****'''<span style="color:#ff0000">Neurotoxicity''' | |||
****'''<span style="color:#ff0000">Peripheral neuropathy''' | |||
****'''<span style="color:#ff0000">Hearing loss''' | |||
== Special scenarios == | == Special scenarios == | ||