Pocket Oncology (Pocket Notebook Series), 1st Ed.

GERM CELL TUMOR

Jarett L. Feldman and George J. Bosl

Epidemiology

• ∼7920 new cases of testicular CA in the US in 2013 (Ca Cancer J Clin 2013; 63:11)

• GCTs are the most common solid tumors in men between the ages of 15 to 35 yo (J Natl Cancer Inst 1995;87:175)

• GCT are seen more commonly in young white men vs. AA

• RFs include cryptorchidism, (orchiopexy should be performed prior to puberty), Klinefelter syndrome (47, XXY karyotype)

• About 50% each seminoma & NSGCT

Biology

• 90% of GCTs originate in the testis & 10% are extragonadal (mostly mediastinal & retroperitoneal, pineal site is rare)

Staging

Initial workup includes: Testicular U/S, radical inguinal orchiectomy, serum tumor markers, CT scan of the chest, abdomen & pelvis & a chest x-ray

AJCC TNMS Staging System for Testis CA (T = tumor, N = node, M = met, S = postorchiectomy nadir serum tumor marker) (AJCC Cancer Staging Manual, 7th ed. New York, Springer, 2009.)

1° Tumor (T): Tis: Intratubular germ cell neoplasia, T1: Tumor limited to the testis & epididymis, T2: Lymphovascular invasion & invasion through the tunica albuginea into the tunica vaginalis, T3:Spermatic cord invasion, T4:Scrotal invasion

Regional LN (N):

Right testis 1° landing zone is the interaortocaval LN

Left testis 1° landing zone is the para-aortic LN

Serum Tumor Markers (S): Postorchiectomy nadir (LDH, hCG (mIU/mL), AFP (ng/mL))

• AFP: Seen in NSGCT only (serum half-life: 5–7d)

• hCG: Seen in both NSGCT & pure seminoma GCTs (serum half-life: 18–36 h)

• LDH: Seen in both NSGCT & pure seminoma GCTs (reflects growth rate, tumor burden, & cellular proliferation)

S0: Markers w/n nl limits: (LDH ULN: ∼250 (lab dependent))

S1: LDH <1.5×ULN, hCG <5000 mIU/mL, AFP <1000 ng/mL

S2: LDH1.5–10×ULN, hCG 5000–50000 mIU/mL, AFP 1000–10000 ng/mL

S3: LDH >10×ULN, hCG >50000 mIU/mL, AFP >10000 ng/mL

Pathology

Histologic dx is critical in the appropriate identification of a GCT subtype

Essentially all GCT have excess 12p copy number, most characterically as an isochromosome of the short arm of chromosome 12, i(12p), w/c can be used as a specific genetic marker of GCT (Cancer Res1992;52:2285–91).

Risk Classification

The IGCCCG created a risk classification for both seminoma & NSGCTs (J Clin Oncol 1997;15:594)

Treatment (NCCN clinical practice guidelines in oncology. 2012)

Key concepts: Initial intervention: Radical inguinal orchiectomy (transscrotal orchiectomy is contraindicated); Do not dose reduce chemotherapy in GCT b/c it results in decreased CR; Carboplatin inferior to cisplatin in treating Pts w/GCT

Seminoma Tx Recommendations:

• Stage I: Surveillance (preferred) vs. RT (dog-leg port RT at a recommended dose of 2000–2550 cGy) vs. carboplatin (primarily in Europe).

• Stage IIA: RT (dog-leg port) or chemotherapy (selected IIB Pts when LN >3 cm) w/c includes either EP × 4 cycles or BEP × 3 cycles

• Stage IIB/C, III (good-risk): Chemotherapy: EP × 4 cycles or BEP × 3 cycles

• Stage IIC, III (Intermediate-risk): Chemotherapy: BEP × 4 cycles

NSGCT Tx Recommendations:

• Stage IA: Surveillance (preferred) or nerve-sparing RPLND

• Stage IB: Nerve-sparing RPLND or chemotherapy or surveillance

After RPLND:

≤2 cm & ≤5 positive LN & no EN invasion: Observation

>2 cm or ≥6 positive LN or any EN invasion: Chemotherapy

• Stage IIA-S0: RPLND (preferred) or chemotherapy (rarely)

After RPLND:

≤2 cm & ≤5 positive LN & no EN invasion: Observation

>2 cm or ≥6 pos LN or any EN invasion: Adjuvant Chemo (2 cycles)

• Stage IIB-S0: Chemotherapy (EP × 4 cycles or BEP × 3 cycles) or RPLND (in special situations)

• Stage IS, IIA-S1, IIB-S1, IIC, IIIA (good-risk): Chemotherapy (EP × 4 cycles or BEP × 3 cycles) commonly followed by surgery (RPLND & residual disease at other sites, if applicable)

• Stage IIIB (intermediate-risk): Chemotherapy (BEP × 4 cycles) or clinical trial if available) commonly followed by surgery (RPLND & residual disease at other sites, if applicable)

• Stage IIIC (poor-risk): Chemotherapy (BEP × 4 cycles or VIP × 4 cycles (selected Pts) or clinical trial if available)

Salvage Therapeutic Options

• 1° gonadal or retroperitoneal disease w/a <6 mos CR: High-dose chemotherapy w/Autologous SCT (N Engl J Med 2007;26: 340; J Clin Oncol 2010;28:1706.) (Preferred) vs. vinblastine, ifosfamide, and cisplatin (VeIP) regimen or TIP regimen

• 1° gonadal disease w/a >6 mos CR: TIP regimen (preferred) (J Clin Oncol 2005;23:6549) vs. High-dose chemo w/Autologous SCT vs. VeIP regimen

• All mediastinal NSGCT requiring salvage chemotherapy (including prior CR & those failing to achieve CR): High-dose chemotherapy w/Autologous SCT (J Clin Oncol 2010;28:1706.) vs. clinical trial

• Progression after salvage conventional-dose chemotherapy: High-dose chemotherapy or clinical trial

Late Toxicities: (JAMA 2008;299(6):672–684.)

• Specific toxicities related to chemotherapy (eg, Bleomycin: Pulmonary tox)

• Cardiac & Hematologic toxicities (ie, Leukemia a/w etoposide)

• Gonadal toxicities: Infertility