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Seminoma Management

85% Stage I, 10% Stage II, 5% Stage III at presentation

Stage I

• Surveillance: 80-85% cured by orchiectomy (15-20% recurrence rate), most relapses occur within 2yrs (< 1% after 5yrs)
• Adjuvant treatment options: carboplatin x1 (recurrence 1-2%), XRT 20-30 Gy (recurrence 1-4%)

Stage II/III

• Lymphadenopathy < 3cm (Stage IIA): XRT 30 Gy (preferred), EP x4, BEP x3 (97% survival)
• Lymphadenopathy > 3cm (Stage IIB/C): EP x4, BEP x3, or XRT 36 Gy

Post-chemotherapy residual masses

• Residual mass > 3cm: residual disease in 30-50%, undergo FDG-PET/CT, if metabolically active consider biopsy/excision, template RPLND can be difficult due to post-chemo desmoplastic reaction
• Residual mass < 3cm: observation, unlikely to contain residual disease (0-4%)
• Necrosis in 90%, viable malignancy in 10%
• No benefit to XRT
• If viable tumor, give adjuvant chemo x2

Relapse

• No prior therapy: consider XRT (70-90% cure)
• Prior XRT: recommend chemotherapy (almost 100% cure)
• Prior carboplatin x1, give cisplatin based chemo
• Prior induction chemo, give second-line chemo (20-50% long-term survival), perform biopsy prior to chemotherapy (increased risk for teratoma)
• Late relapse is uncommon, consider cisplatin-based therapy

NSGCT Management

33% Stage I, 33% Stage II, 33% Stage III at presentation

Stage IA-IB

• Options: offer observation, BEP x1-2, or RPLND (both with almost 100% cure)
• Surveillance:20-30% relapse if IA, 40-50% relapse if IB
• Consider treating: if LVI and embryonal carcinoma present (> 45-90% primary), increased risk for relapse relapse (30-90% risk vs baseline < 20%)
• Timing:> 90% relapses occur within 2yrs, but 1-5% will occur 5+yrs later
• Somatic malignancy: if present in orchiectomy specimen, recommend RPLND (non-responsive to chemotherapy

Stage IS

• 37-100% eventually develop elevated STMs or RP metastases
• Management: induction chemotherapy, > 90% cancer-specific survival

Stage IIA

• Normal STMs: offer BEP x3, EP x4, or RPLND
• Teratoma present: recommend RPLND
• Elevated STMs or LN > 3cm, recommend chemotherapy
• Prior inguinal surgery: recommend chemo (risk of abnormal lymphatic drainage)

Stage IIB

• All patients: offer BEP x3 or EP x4
• RPLND alternative but most patients will need adjuvant chemo due to risk of relapse

Stage IIC + III

• All patients: induction chemotherapy, regimen based on IGCCCG classification
• Salvage chemo: give for post-chemo marker elevation or disease progression
• RPLND: only for post-chemo RP nodes > 1cm
• Teratoma may be present even if not seen in primary specimen

Post-chemotherapy residual masses

• Up to 40% contain residual teratoma
• Residual mass < 1cm: observe, unlikely to contain malignancy, only 9% recur (only 4% in RP)
• Residual mass > 1cm: full bilateral template RPLND
• Residual mass after salvage chemo: RPLND recommended no matter residual mass size, high risk for containing cancer (50%) or teratoma (40%)

Relapsed disease

• No prior chemotherapy: induction chemotherapy has 95% cure rate
• Prior chemotherapy: consider TIP, VIP, or high-dose chemo
• Prior chemotherapy with residual/new mass: recommend surgical resection
• Elevated STMs despite 1st/2nd line chemo: consider "desperation surgery" if potentially resectable single site, with 33-57% long-term survival
• Late relapse (> 2yrs): may be viable malignancy (54-88%), teratoma (12-28%), or malignant transformation (10-20%), usually managed with surgical resection (chemo-resistant)

Brain metastases

• Seen mainly with choriocarcinoma, mortality 4-10% due to hemorrhage
• Brain relapse worse prognosis than brain mets at initial diagnosis
• Management: BEP x4 then mass resection

Adjuvant therapies

Chemotherapy

• Primary options: EP x4 vs BEP x3 for good risk patients, BEP x4 for intermediate/poor risk patients, VIP x4 if contraindication to bleomycin (pulmonary concerns)
• Salvage options: VeIP, TIP, high-dose chemo + autologous SCT
• Cisplatin vs carboplatin: do not use carboplatin for good risk metastatic patients, can use carboplatin for Stage IA-IB seminoma
• General early toxicity: fatigue, myelosuppression, infection, neuropathy, hearing loss, decreased renal function, mortality (0-4%)
• General late toxicity: neuropathy (14-43%), Raynaud syndrome (20-45%), ototoxicity (20-40%), hypogonadism (20-25%), infertility, secondary malignancy, cardiac disease
• Post-bleomycin surgical management: prevent complications with aggressive monitoring, avoid over-hydration, use colloids, "judicious" crystalloids, keep FIO₂ < ;0.25

Chemo agent	Mechanism	Toxicity
Bleomycin	Binds/breaks DNA	Pneumonitis, pulmonary fibrosis
Etoposide	Binds DNA	Myelosuppression, mucositis, 0.8% leukemia risk
Cisplatin	Crosslinks DNA	Nephrotoxicity, neurotoxicity, hearing loss, cardiomyopathy

RPLND

• Template limits: renal vessels superiorly, ipsilateral ureter crossing iliacs inferiorly, ipsilateral ureter laterally, aorta/common iliac inferior to IMA, and contralateral ureter (R side) vs vena cava (L side) above IMA
• Right modified template: remove right common iliac, paracaval, precaval, retrocaval, interaortocaval, preaortic, and retroaortic nodes
• Left modified template: remove left common iliac, paraaortic, preaortic, retroaortic nodes
• Bilateral template indications: Stage II NSGCT, suspicious intraoperative nodes, pcRPLND, somatic malignancy in primary
• Remove ipsilateral gonadal vessels and spermatic cord remnant
• Size cutoff of 1cm for primary RPLND has a high false negative rate, have increased suspicion for LN > 5-9mm in primary landing zone
• pcRPLND findings: 40% necrosis, 45% teratoma, 15% viable malignancy
• Use clinical judgement for unilateral vs bilateral RPLND for clinically negative nodes
• Use adjuvant chemotherapy if pN2-3 with viable tumor
• Ejaculatory dysfunction: common, caused by post-ganglionic sympathetic nerve and hypogastric plexus injury, nerve sparing preserves ejaculatory function 99% of the time
• Complications: anejaculation, chylous ascites (2%), renal vascular injury (3%), bowel obstruction (1-3%), mortality (0.3%, higher for pcRPLND)

Radiation (seminoma only)

• Success: prevents relapse in 96% Stage I seminoma
• Templates: abdominal retroperitoneum if seminoma IA/IB, add ipsilateral iliac nodes for IIA/IIB (can consider for IA/IB as well)
• Radiate inguinal scar or ipsilateral scrotum if scrotal violation or tumor spillage occurred during surgery
• Potential contraindications: prior XRT, inflammatory bowel disease, pelvic/ectopic kidney (very radiosensitive)
• XRT side effects: nausea/vomiting, ulcers (< 5%), diarrhea, oligospermia, secondary malignancy (18% at 25yrs)