Editing Germ Cell Tumours (section)

===== CSIA and IB NSGCT =====

* '''<span style="color:#ff0000">Options:</span>'''
*# '''<span style="color:#ff0000">Surveillance</span>'''
*# '''<span style="color:#ff0000">Adjuvant primary RPLND</span>'''
*# '''<span style="color:#ff0000">Adjuvant primary chemotherapy (BEPx1-2)</span>'''
*#* '''Newer guidelines, such as 2019 AUA guidelines, recommend 1 cycle for CSIA and 2 cycles for CSIB'''
*#* '''2010 CUA Consensus Statement: BEPx2'''
** Long-term survival approaches 100% for each
** '''Guidelines''':
*** '''2010 CUA Consensus Statement: surveillance preferred for all CSI NSGCT'''
*** '''<span style="color:#ff0000">2019 AUA Guidelines:</span>'''
**** '''<span style="color:#ff0000">CSIA NSGCT: surveillance recommended</span>'''
**** '''<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">Surveillance for clinical stage I NSGCT</span>'''
** 70-80% of patients with clinical stage I seminoma achieve cure with radical orchiectomy alone
** '''<span style="color:#ff0000">Risk factors for relapse on surveillance (2):</span>'''
**# '''<span style="color:#ff0000">Pre-dominant embryonal carcinoma</span>'''
**# '''<span style="color:#ff0000">Lymphovascular invasion</span>'''
*** The definition of EC predominance in the literature varies from 45-90%.
*** Other identified risk factors include advanced pT stage, absence of mature teratoma, absence of yolk sac tumor, presence of EC (regardless of the percent composition), percentage of MIB-1 staining, tumor size, and patient age.
** Surveillance protocol varies by institution, no consensus
*** History and physical examination: every 2-3 months in year 1, every 2-4 months in year 2, every 4-6 months in year 3, and every 6-12 months for years 4 and 5
*** Serum tumor markers (AFP, hCG +/- LDH): every 2-3 months in year 1, every 2-4 months in year 2, every 4-6 months in year 3, and every 6-12 months for years 4 and 5
*** Radiologic assessment (chest x-ray and imaging of the abdomen with or without the pelvis): every 3-6 months in year 1 starting at 3 months, every 4-12 months in year 2, once in year 3, and once in year 4 or 5.
**** Men at higher risk of relapse (e.g., lymphovascular invasion) should be imaged with shorter intervals.
**** >90% of relapses occur within the first 2 years, but late relapses (>5 years) are seen in 1% of patients; after this time, annual serologic and radiographic assessment may be performed as indicated based upon clinical concerns.
***** Compared with NSGCT, surveillance for CS I seminoma is needed for a longer period because 10% to 20% of relapses occur 4 years or more after diagnosis.
** Patients who relapse on surveillance should be fully restaged and treated based on their TNM-s status.
** Early and late relapses have similar prognosis
* '''Adjuvant primary RPLND'''
** Primary RPLND should be performed with curative (rather than staging) intent in all patients.
** Full, bilateral template dissection is associated with the lowest risk of abdominopelvic recurrence (<2%) and the highest rate of antegrade ejaculation (>90%) when nerve-sparing techniques are employed.
** A multi-center randomized trial comparing primary RPLND to chemotherapy for CS I found that chemotherapy was associated with a lower risk of relapse. The relapse rate after primary RPLND in this trial was 11%, higher than other published series, suggesting that RPLND should be performed in experienced centers.
* '''Adjuvant primary chemotherapy'''
** BEP x 1-2 is typically used.
** Advantages (2):
**# '''Highest relapse-free survival with any single treatment modality'''
**# Can be delivered at community-based institutions
** Disadvantages (4):
**# Does not treat retroperitoneal teratoma
**# Long-term surveillance CT imaging of the retroperitoneum is required
**# Potential risk of late toxicity (see below).
**#* The risk of late toxicity from 2 cycles of chemotherapy is poorly defined, although there appears to be no safe lower limit.
**# Exposes patients to the potential for chemoresistant and/or late relapse
**#* Although primary chemotherapy is associated with the lowest risk of relapse, these relapses are less amenable to salvage therapy because they are chemoresistant, particularly if they have received a regimen other than standard dose BEP. In contrast, patients who relapse after RPLND or on surveillance are chemotherapy-naive and are cured with chemotherapy in virtually all cases.