Editing Germ Cell Tumours (section)

==== Seminoma ====

===== CSIA and IB Seminoma =====

* '''<span style="color:#ff0000">Options (3):</span>'''
** '''<span style="color:#ff0000">Preferred (1): surveillance</span>'''
** '''<span style="color:#ff0000">Alternatives (2):</span>'''
**# '''<span style="color:#ff0000">Adjuvant primary radiotherapy (20 Gy to the para-aortic region)</span>'''
**# '''<span style="color:#ff0000">Adjuvant primary chemotherapy with single-agent carboplatin (1 cycle)</span>'''
** '''<span style="color:#ff0000">Both 2019 AUA and 2010 CUA guidelines recommend surveillance, adjuvant as an alternative</span>'''
*** '''If adjuvant treatment is chosen'''
**** '''CUA recommends radiotherapy over chemotherapy'''
**** '''EAU recommends against radiotherapy'''
**** '''SWONTECA recommends radiotherapy only if chemotherapy not suitable'''
** Long-term survival rates approaching 100% for each approach
** '''<span style="color:#ff0000">Surveillance for clinical stage I seminoma</span>'''
*** 80-85% of patients with clinical stage I seminoma achieve cure with radical orchiectomy alone
*** Protocol varies by institution, no consensus
**** History and physical examination: every 4-6 months for the first 2 years, and then every 6-12 months in years 3-5.
**** Cross-sectional imaging of the abdomen with or without the pelvis: every 4-6 months for the first 2 years, and then every 6-12 months in years 3-5.
**** Imaging of the chest and serum tumor marker assessment can be obtained as clinically indicated.
***** Compared with NSGCT, surveillance for CS I seminoma is complicated by the limited utility of serum tumor markers to detect relapse
*** '''<span style="color:#ff0000">Risk factors for relapse on surveillance (2):</span>'''
**** '''<span style="color:#ff0000">Tumor size >4 cm</span>'''
**** '''<span style="color:#ff0000">Rete testis invasion</span>'''
*** Patients who relapse on surveillance should be fully restaged and treated based on their TNM-s status.
** '''Adjuvant primary radiotherapy'''
*** Delivered as dog-leg (retroperitoneum and ipsilateral pelvis) vs. para-aortic region
**** Dog-leg
***** Outcomes
****** In-field recurrence after dog-leg radiotherapy occurs in <1%.
******* Most common sites of recurrence are the thorax and left supraclavicular fossa.
******* Virtually all recurrences are cured with first-line chemotherapy.
****** Persistent oligospermia after dog-leg radiotherapy occurs in 8%
***** Advantage
****** Does not require serial follow-up CT imaging after treatment
**** Para-aortic
***** Advantage
****** Smaller field and dose.
***** Disadvantage
****** Requires serial follow-up CT imaging after treatment
**** Dog-leg vs. para-aortic
***** RTC found para-aortic to be non-inferior to dog-leg radiotherapy in CSI seminoma[https://pubmed.ncbi.nlm.nih.gov/21212385/ §]
** '''Adjuvant primary chemotherapy'''
*** Cisplatin is inferior to carboplatin for CSI seminoma
*** Patients require serial follow-up CT imaging

===== CS IIA and IIB Seminoma =====

* ≈15-20% of patients with seminoma have CS II disease at diagnosis; 70% of these patients have CS IIA and IIB.
* '''<span style="color:#ff0000">CSIIA:</span>'''
** '''CUA: Dog-leg radiotherapy (25-35 Gy) preferred over first-line chemotherapy (BEP×3 or EP×4)'''
** '''AUA: radiotherapy or chemotherapy'''
* '''<span style="color:#ff0000">CSIIB:</span>'''
** '''CUA: depending on bulk of disease and location of lymph nodes, radiation or chemotherapy [good risk chemotherapy BEP×3 or EP×4] can be used.''' 
*** '''First-line chemotherapy is recommended for bulky (>3 cm) and/or multifocal retroperitoneal metastases'''
** '''AUA:'''
*** '''CSIIB with lymph node ≤3cm: radiotherapy or chemotherapy'''
*** '''CSIIB with lymph node >3cm: chemotherapy'''
* Routine surveillance CT imaging is unnecessary after complete resolution of disease.
*'''<span style="color:#ff00ff">Surgery in Early Metastatic Seminoma (SEMS) Trial</span>'''
**Study design: Phase II trial
**55 patients with pure testicular seminoma after radical orchiectomy with isolated retroperitoneal lymphadenopathy 1-3 cm in greatest dimension. 
***No more than 2 lymph nodes could be enlarged radiographically and lymph nodes needed to be within the ipsilateral RPLND template
***Lymph node enlargement could be synchronous (stage IIA or IIB) or metachronous (stage I with recurrence).
***Open RPLND was performed by certified surgeons who performed ≥8 open RPLND surgeries in the year before site initiation or at least 25 open RPLND surgeries with the past 3 years
**Primary outcome: 2-year relapse-free survival
**Results
***Median follow-up after RPLND: 33 months
***In post-RPLND follow-up, one patient received a single cycle of carboplatin for pN2, all other patients were managed with surveillance
***Pathological nodal stage
****pN0: 16%
****pN1: 22%
****pN2: 56%
****pN3: 5%
***2-year relapse-free survival: 81% (86% cN1 vs. 64% cN2, p=0.04)
***2-year overall survival: 100%
**[https://pubmed.ncbi.nlm.nih.gov/36913642/ Daneshmand, Siamak, et al.] "Surgery in Early Metastatic Seminoma: A Phase II Trial of Retroperitoneal Lymph Node Dissection for Testicular Seminoma With Limited Retroperitoneal Lymphadenopathy." ''Journal of Clinical Oncology'' (2023): JCO-22.

===== CSIIC and III seminoma =====

* '''Regimen and number of cycles are based on IGCCCG risk classification''' (see above)
** '''Good-risk: BEP×3 or EP×4'''
** '''Intermediate-risk: BEP×4'''

===== Special scenarios =====

====== Residual masses after chemotherapy for seminoma ======
* '''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">Necrosis 90%</span>'''
** '''<span style="color:#ff0000">Viable malignancy: 10%</span>'''
** '''Compared to NSGCT, residual masses after chemotherapy are much more likely to be necrosis (for NSGCT, histology of post-chemotherapy residual masses: necrosis in 40%, viable disease in 15%, and teratoma in 45% (see below)).'''
* '''<span style="color:#ff0000">Management</span>'''
** '''<span style="color:#ff0000">In seminoma, most residual masses do not need to be treated.</span>'''
*** '''Spontaneous resolution of post-chemotherapy residual masses is reported in 50-60% of cases, and the median time to resolution is 13-18 months.'''
*** <span style="color:#ff0000">'''Post-chemotherapy surgery for seminoma is technically difficult'''</span> (and frequently not feasible) because of the desmoplastic reaction that occurs after chemotherapy with resultant increased perioperative morbidity.
*** Teratoma and malignant transformation are much less of a concern with advanced seminoma.
** '''<span style="color:#ff0000">If residual masses > 3 cm, evaluate further with FDG-PET</span>'''
*** '''<span style="color:#ff0000">If FDG-PET positive: post-chemotherapy surgery</span>'''
*** '''<span style="color:#ff0000">If FDG-PET negative: 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

====== 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 ======

* '''If chemo-naïve:'''
** '''Patients relapsing on surveillance should receive primary radiotherapy'''
** '''Patients with CSI or II seminoma treated with radiotherapy, or those on surveillance that relapse with bulky''' (>3 cm) '''retroperitoneal masses and systemic relapse should receive first-line chemotherapy based on ICCCG risk category'''
*** Salvage rates approach 100%.
* '''If early relapse after chemotherapy: salvage chemotherapy'''
** An important consideration for patients with advanced seminoma who relapse after first-line chemotherapy is the potential for teratoma at the site of relapse.
** Patients with normal serum tumor markers should undergo biopsy before starting second-line chemotherapy'''.'''