MULTIDISCIPLINARY GENITOURINARY ONCOLOGY COURSE

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Katherine Warner
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1 MULTIDISCIPLINARY GENITOURINARY ONCOLOGY COURSE Case 2 Testicular Cancer Nuno Sineiro Vau Medical Oncologist Champalimaud Foundation, Lisbon October 2017

2 Male, 36 year-old, sales manager. Past medical history NKDA. Smoker. No drinking habits. Migraine. No family history of oncological diseases. Medication Morphine. Acetaminophen. Alprazolam.

3 Aug 14 Backache Sep 14 Worsening backache. Unremarkable blood tests (decreasing MCV: fl). Thoracic and lumbar spine CT scan unremarkable. Oct 14 Testicular swelling and pain. LDH 1755 U/L; AFP 14 ng/ml and hcg miu/l. Testicular ultrasound: Suspicious right testicular nodule.

4 Oct 14 (Cont.) Nov 14 TAP CT: Multiple lung metastasis; multiple enlarged thoracic lymph nodes; multiple liver metastasis; massive retroperitoneal lymph node conglomerate (12,8 x 11,7 x 8,2 cm), compressed inferior VC. Backache, asthenia and headache. PS0. PE: Epigastric mass. Analgesia adjustment. Started LMWH. Refused sperm preservation. Lung function tests normal. Brain MRI normal

5 Nov 14 (Cont.) Surgery: right orchiectomy. Histology: Mixed germ cell tumour ( Choriocarcinoma 70%; Seminoma 30%); 3.3 cm; V1; rete testis invasion. Without invasion of spermatic cord, tunica albuginea nor tunica vaginalis. LDH 1971 U/L; AFP 16 ng/ml and hcg miu/l. Hg 7,9 g/dl; ALP 255 U/L; TGO 48 U/L; TGP 60 U/L; GT 212 U/L; Total Bili 3,3 mg/dl. Staging: IIIC (pt2cn3m1bs3) poor risk (IGCCCG).

6 Nov 14 (Cont.) Started chemotherapy BEP (75% VP16). During C1 admitted due to fatigue G3, anaemia G3, neutropenia G3, Pharyngitis G2. Backache remission. Decreasing epigastric mass. Increasing (CT scan) liver and nodal metastasis. C1d21: LDH 1031 U/L and hcg miu/l Unfavourable TTN (Fizazi K et al. J Clin Oncol 2004). Started BEP C2 (100% VP16). During C2 admitted due to fatigue G3 and pancytopenia.

7 Dec 14 C2d28 LDH 851 U/L and hcg 2575 miu/l. Dose intensification GETUG 13 (Fizazi K et al. Lancet Oncol 2014). Started C1 P-BEP-OXA + G (Paclitaxel 175 mg/m2 d1 before BEP plus Oxaliplatin 130 mg/m2 day 10). C3d7 Admitted febrile neutropenia G4. Generalized oedema. Pharyngitis G3. Anemia G2. Thrombocytopenia G3. Hypoalbuminemia G3. Anorexia G3. Weight loss G2. PS 2-3. C3d8 Christmas Miracle. C3d10 Omitted Oxaliplatin.

8 Jan 15 C3d28 LDH 364 U/L and hcg 246 miu/l. C3d35 Paresthesia G3. Stopped dose intensification strategy. Started BEP C4 (PEG and prophylactic Ciprofloxacin and Fluconazole). C4d9 Admitted. Worsening fatigue G3. Anemia G3. Hyponatremia G3.

9 Mar 15 Paresthesia G3. Fatigue G2. Prolonged hyponatremia. LDH 217 U/L, AFP 9,9 ng/ml and hcg 3,4 miu/l. TAP CT (PR): Lung PR (biggest 17 8 mm). ccr thoracic lymph nodes. Liver PR (biggest 8,5 4 cm). Major abdominal lymph nodes PR (12 2,8 cm). Apr 15 LDH 250 U/L, AFP 6,8 ng/ml and hcg 3,1 miu/l. PET -TAC FDG: Increased uptake in multiple liver metastasis, in a retroperitoneal lymph node and in a lung metastasis

11 Apr 15 (Cont) Referred for HDC-ASCT. Jun 15 Surgery: Liver biopsy. Retroperitoneal lymphadenectomy. Pulmonary nodule resection. Histology: All 3 samples without viable neoplastic tissue.

12 Jul 15 Paresthesia G3. Fatigue G1. PS1. LDH 254 U/L, AFP 5 ng/ml and hcg 2,34 miu/l. PET -TAC FDG: Increased uptake in multiple liver metastasis and de novo in retroperitoneal and pelvic lymph nodes. Lung uptake attributed to prior surgery.

13 Set 15 Paresthesia G2-3. PS1. LDH 332 U/L, AFP 4,9 ng/ml and hcg 2,5 miu/l. W&W Oct 15 Paresthesia G2-3. PS1. LDH 354 U/L, AFP 7,2 ng/ml and hcg 2,2 miu/l. TAP CT: Lung alterations due to prior surgery. Stable hepatic metastasis ( central necrosis). Multiple small retroperitoneal lymph nodes. W&W

14 Dec 15 to present date Last appointment 4 days ago. Paresthesia G2-3. Retired. Depression. PS1. Without biochemical progression. Serial CT scan (last one this week) with stable liver lesions. Without other evidence of disease W&W

16 Fizazi K et al. Early Predicted Time to Normalization of Tumor Markers Predicts Outcome in Poor-Prognosis Nonseminomatous Germ Cell Tumors. J Clin Oncol Evaluate the prognostic relevance of the rate of decline of serum alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy. N= 653. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN) TTN was associated with both PFS (P <0.0001) and OS (P<0.0001). OS4y were 83% and 58%. This effect was independent from the initial S, the primary tumor site, and the presence of nonpulmonary visceral metastases PF S OS

17 Fizazi K et al. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol Assess whether treatment intensification based on an early tumour marker decline will improve PFS in IGCCCG poor risk. BEP1 HCG and AFP measured d18-21: Favourable TTN 3xBEP Unfavourable TTN Randomization: 3xBEP vs. Dose-dense [(P 175 d1 + BEP + OXA 130 d10) x2 (DDP 100 d1 + IFF 2 d10,12 and 14 + Bleo 25U qd d10 to 14)x2] + G. n= % favourable TTN and 80% unfavourable TTN. PFSV3y: 59% Unfav-dose-dense vs. 48% Unfav-BEP vs. 70% Fav-BEP. More G34 neurotoxicity (7% vs 1%) and more haematotoxicity; BUT no difference in FN (17% vs 18) or toxic deaths (1% in both groups). Salvage HDCT plus stem-cell transplant in 6% Unfav-dose-dense vs. 16% in Unfav-BEP.

18 Treglia G et al. Diagnostic performance of fluorine-18- fluorodeoxyglucose positron emission tomography in the postchemotherapy management of patients with seminoma: systematic review and meta-analysis. Biomed Res Int 2014;2014. Pooled analysis demonstrated a sensitivity of 78%, a specificity of 86%, PPV of 58%, NPV of 94%, and accuracy of 84%. A better diagnostic accuracy of FDG PET or PET/CT in evaluating residual or recurrent lesions greater than 3 cm compared with those less than 3 cm. Oechsle K et al. [18F] Fluorodeoxyglucose positron emission tomography in nonseminomatous germ cell tumors after chemo- therapy: the German multicenter positron emission tomography study group. J Clin Oncol Prospective study. Evaluates the accuracy of FDG PET in NSGCT for the prediction of histology compared with CT and serum tumor markers. n=121. Pts with IIC or III NSGCT scheduled for resection after DDP-based CT. FDG PET performed after CT. Prediction of tumor viability with FDG PET was correct in 56%. It was not better than the accuracy of CT (55%) or serum tumor markers (56%). Sensitivity and specificity of FDG PET were 70% and 48%. PPV were not different (55%, 61%, and 59% for CT, STM and PET, respectively). In NSGCT, FDG-PET is less helpful in predicting histology in residual masses after chemotherapy than in patients with pure seminoma.

Germ Cell Tumors. Karim Fizazi, MD, PhD Institut Gustave Roussy, France

Germ Cell Tumors. Karim Fizazi, MD, PhD Institut Gustave Roussy, France Germ Cell Tumors Karim Fizazi, MD, PhD Institut Gustave Roussy, France Surveillance for stage I GCT NSGCT A 26 year-old patient had a orchiectomy revealing embryonal carcinoma (40%), seminoma (40%) and