Editing Germ Cell Tumours (section)

===== CS IIA and IIB NSGCT =====

* '''<span style="color:#ff0000">CSIIA with positive markers or CSIIB regardless of markers: primary chemotherapy (recommended by both CUA and AUA)</span>'''
** CUA: Elevated AFP or hCG levels after orchiectomy or bulky lymph nodes (>3cm) are risk factors for recurrence after primary RPLND. Therefore, patients with CS IIA and IIB NSGCT and elevated AFP or hCG levels or bulky lymph nodes (>3 cm) should receive induction chemotherapy.
** AUA: Clinicians may offer RPLND as an alternative to chemotherapy to select patients with clinical stage IIB NSGCT with normal post-orchiectomy serum AFP and hCG.
* '''<span style="color:#ff0000">CSIIA disease without marker elevation</span>'''
** Substantial proportion of men with clinical stage IIA NSGCT are over-staged
** Minority of men with clinical stage IIA are upstaged to pathological stage IIB and may be advised to receive two cycles of adjuvant chemotherapy
** '''<span style="color:#ff0000">CUA: RPLND (with or without adjuvant chemotherapy) or surveillance with surgery for stable or growing lesions (if becomes marker positive use primary chemotherapy)</span>'''
** '''AUA: RPLND or chemotherapy'''
* '''Management after primary RPLND for NSGCT based on pathology (2021 NCCN''' TEST-10'''/2019 AUA):'''
** '''pN0: surveillance'''
** '''pN1: surveillance (preferred) vs. chemotherapy''' (BEP x2 or EP x2)
** '''pN2: chemotherapy''' (BEP x2 or EP x2) '''(preferred) vs. surveillance'''
** '''pN3: chemotherapy''' (BEP x3 or EP x4)
** '''pN1-3 pure teratoma: surveillance'''
** '''<span style="color:#ff00ff">Immediate vs. deferred chemotherapy for pathological stage II disease after primary RPLND</span>'''
*** Population: 195 males found to have positive nodes, (pathologically stage II) after primary RPLND (in whom the procedure was indicated). Nodes had to be considered completely resected and tumor markers had to be normal after primary RPLND.
*** Randomized to immediate vs. delayed chemotherapy (cisplatin/vinblastine/bleomycin +/- dactinomycin/cyclophosphamide)
*** Results:
**** Median follow-up: 4 years
**** Relapse rate at 2 years: 6% immediate vs. 49% delayed chemotherapy
**** Cancer-specific deaths: 1 immediate vs. 3 delayed chemotherapy
**** Death from all causes: 5 immediate vs. 3 delayed chemotherapy
*** Conclusions: immediate chemotherapy in patients found to have pathological stage II after primary RPLND reduces risk of relapse, but no significant difference in cancer-specific or overall survival (though really few deaths)
*** Williams, Stephen D., et al. "[https://pubmed.ncbi.nlm.nih.gov/2446132/ Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer.]" ''New England Journal of Medicine'' 317.23 (1987): 1433-1438.
* '''Disadvantage of chemotherapy for metastatic NSGCT'''
*# '''Teratoma is resistant to chemotherapy'''
** '''RPLND is preferred as initial therapy in patients at risk for retroperitoneal teratoma who are at otherwise low risk for systemic disease''' (normal serum tumor markers, lymphadenopathy <3 cm).
** Unresected teratoma has the potential to exhibit rapid growth (growing teratoma syndrome), undergo malignant transformation, or cause late relapse, all of which may have lethal consequences.
* '''<span style="color:#ff0000">Growing teratoma syndrome</span>'''
** '''<span style="color:#ff0000">Should be considered if there is an expected tumour marker decline during chemotherapy but the metastases are growing radiologically</span>'''
** '''<span style="color:#ff0000">Management</span>'''
*** '''<span style="color:#ff0000">2010 CUA Guidelines: In most cases, the full course of chemotherapy should be completed and resection of the growing and residual masses should be done post-chemotherapy.</span>'''
**** Very rarely, rapid radiological progression in the setting of decreasing tumour marker decline is seen which would necessitate surgical resection prior to the completion of chemotherapy.
***** Similar description in 2018 AUA Update on on Medical and Surgical Management of Advanced Testis Cancer
***** Campbell's 11th edition, Chapter 34, page 805: Special mention is made of patients with declining or normalized serum tumor markers during first-line chemotherapy with enlarging (usually cystic) masses. These patients are considered to have growing teratoma syndrome. In these rare cases, chemotherapy is temporarily interrupted, and patients are taken for surgical resection. With complete surgical resection, the long-term prognosis for these patients is favorable