Testicular CancerTesticular Cancer

Ryan MillsRyan Mills

Pharm D. candidatePharm D. candidate

May 3, 2007May 3, 2007

• H&P:H&P: A.M is a 23-year-old A.M is a 23-year-old Mexican American male who has a 1-Mexican American male who has a 1-year history of a right testis mass. He year history of a right testis mass. He recently presented with right flank recently presented with right flank pain. Work up showed several pain. Work up showed several pulmonary metastases as well as pulmonary metastases as well as retroperitoneal metastasis and right retroperitoneal metastasis and right hydronephrosis. His scrotal hydronephrosis. His scrotal ultrasound revealed several lesions.ultrasound revealed several lesions.

• PMH/Medications:PMH/Medications: Noncontributory. Noncontributory.

• Allergies:Allergies: NKDANKDA

February 28, 2007:February 28, 2007:

1.1. U/S scrotum: right testicular U/S scrotum: right testicular multiple masses compatible with multiple masses compatible with primary malignancy of the testes. primary malignancy of the testes.

2.2. CT scan abdomen, pelvis and chest: CT scan abdomen, pelvis and chest: metastatic disease to the lungs and metastatic disease to the lungs and invasion of the tumor into the invasion of the tumor into the inferior vena cava and right kidney. inferior vena cava and right kidney.

3.3. U/S kidney: massive retroperitoneal U/S kidney: massive retroperitoneal lymphadenopathy.lymphadenopathy.

March 1, 2007:March 1, 2007:

• Right inguinal orchiectomy: Right Right inguinal orchiectomy: Right testis and spermatic cord were sent testis and spermatic cord were sent to pathology to determine prognosis. to pathology to determine prognosis.

March 2, 2007March 2, 2007

• Patient D/C pending pathology Patient D/C pending pathology results. results.

ResultsResults

• Right orchiectomy showed, Right orchiectomy showed, Nonseminomatous germ cell tumor Nonseminomatous germ cell tumor of testis, T2 N3 M1, S2, (AFP 427, of testis, T2 N3 M1, S2, (AFP 427, LDH 1853), stage III.LDH 1853), stage III.

• IMPRESSION AND PLAN:IMPRESSION AND PLAN: Available Available data support diagnosis of primary data support diagnosis of primary right testis nonseminomatous right testis nonseminomatous cancer, predominantly seminoma but cancer, predominantly seminoma but possibly with other histologic possibly with other histologic components, with high LDH and AFP, components, with high LDH and AFP, metastatic to periaortic nodes, right metastatic to periaortic nodes, right inguinal region and lungs. The inguinal region and lungs. The patient is "intermediate risk" based patient is "intermediate risk" based on his markers and metastases. Plan on his markers and metastases. Plan to start BEP chemotherapy. to start BEP chemotherapy.

Delbes G, Hales BF, Robaire B. Delbes G, Hales BF, Robaire B. Effects of the chemotherapy cocktail Effects of the chemotherapy cocktail used to treat testicular cancer on used to treat testicular cancer on sperm chromatin integrity. J Androl. sperm chromatin integrity. J Androl. 2007 Mar-Apr;28(2):241-9; 2007 Mar-Apr;28(2):241-9; discussion 250-1. Epub 2006 Oct 4.discussion 250-1. Epub 2006 Oct 4.

•

March 5, 2007:March 5, 2007:

Patient readmitted: surgical site pain, Patient readmitted: surgical site pain, SOB & pain radiating down his right SOB & pain radiating down his right leg.leg.

• CT chest: PE with multiple lesions of CT chest: PE with multiple lesions of varying sizes. varying sizes.

• Nasal Cannula-SOBNasal Cannula-SOB

March 6, 2007:March 6, 2007:

CT right leg: Mass extending into right CT right leg: Mass extending into right inguinal canal.inguinal canal.

March 9, 2007:March 9, 2007: CT brain negative. CT brain negative.

March 16, 2007March 16, 2007::    

• Endoscopy duodenem: extrinsic Endoscopy duodenem: extrinsic gastric compression and upper gastric compression and upper esophageal injury.esophageal injury.

March 23,2007:March 23,2007: Febrile Neutropenia: Febrile Neutropenia: ID recommendationsID recommendations

• VancomycinVancomycin

• MerepenemMerepenem

• Levofloxacin (ARF contraindicates Levofloxacin (ARF contraindicates AMG)AMG)

• CaspofunginCaspofungin

April 04, 2007:April 04, 2007:

Bronchoscopy: bilateral pulmonary Bronchoscopy: bilateral pulmonary infiltrate. infiltrate.

April 09,2007:April 09,2007:

Culture: Culture: Candida species present. Rare large Candida species present. Rare large yeast with broad-yeast with broad-based budding form.based budding form.

April 10, 2007:April 10, 2007: Started Itraconazole Started Itraconazole x 6 months. Indication: Blastomyces x 6 months. Indication: Blastomyces per IDper ID

April 19, 2007:April 19, 2007: Febrile Neutropenia Febrile Neutropenia (Standard Protocol)(Standard Protocol)

• CefepimeCefepime

• VancomycinVancomycin

• LevofloxacinLevofloxacin

• CHEMOTHERAPY: CHEMOTHERAPY: Bleomycin/Etoposide/Cisplatin x 4 cycles Bleomycin/Etoposide/Cisplatin x 4 cycles (21 day intervals)(21 day intervals)

• Weekly CBC, Plt, lytes, Mg++, Phos, LDH, Weekly CBC, Plt, lytes, Mg++, Phos, LDH, AFPAFP

• NOTE: Before chemotherapy. ANC <1000, NOTE: Before chemotherapy. ANC <1000, Hemoglobin <8.5, platelets <100,000, Hemoglobin <8.5, platelets <100,000, abnormal creatinine or liver function tests.abnormal creatinine or liver function tests.

• Day 21 with CT-chest, abdomen, CBC, Plt, Day 21 with CT-chest, abdomen, CBC, Plt, lytes, Mg++, Phos, LDH, AFP.lytes, Mg++, Phos, LDH, AFP.

• Hydrate with NS 150ml/hr during Hydrate with NS 150ml/hr during treatment treatment

CHEMORXCHEMORX

1.1. Etoposide: QD x 5dEtoposide: QD x 5d

2.2. Cisplatin: QD x 5dCisplatin: QD x 5d

3.3. Bleomycin: Days 2,9,16 Bleomycin: Days 2,9,16

• March 10 Cycle # 1March 10 Cycle # 1

• April 4 Cycle # 2April 4 Cycle # 2

• April 30 Cycle # 3 April 30 Cycle # 3

Note: 21d intervals extended b/c not Note: 21d intervals extended b/c not meeting criteria. i.e meeting criteria. i.e afbrile/neutropenicafbrile/neutropenic

EpidemiologyEpidemiology

• Most frequently occuring Most frequently occuring malignancies in young men.malignancies in young men.

• Most common in males ages 20-35Most common in males ages 20-35• Uncommon after the age of 40. Uncommon after the age of 40.

Therefore accounts for only 1% of Therefore accounts for only 1% of malignancies in males.malignancies in males.

• Whites are at a higher risk than Whites are at a higher risk than African AmericansAfrican Americans

Risk FactorsRisk FactorsCryptorchidism (Undescended Testicle: Cryptorchidism (Undescended Testicle:

intraabdominal higher risk vs. inguinal)intraabdominal higher risk vs. inguinal)

Caucasian (4-5 x risk) Caucasian (4-5 x risk)

Testicular cancer contralateral testisTesticular cancer contralateral testis

Klinefelters syndromeKlinefelters syndrome

HIV pos.HIV pos.

SymptomsSymptoms

• Asymptomatic nodule or swellingAsymptomatic nodule or swelling

• Testicular mass, feeling of heaviness, Testicular mass, feeling of heaviness, pain and/or hardnesspain and/or hardness

Advance DiseaseAdvance Disease may experiencemay experience

Abdominal pain: RP adenopathyAbdominal pain: RP adenopathy

Gynecomastia: elevated b-HCGGynecomastia: elevated b-HCG

Dyspnea: pulmonary metastasesDyspnea: pulmonary metastases

HA/seizure: brain metastasesHA/seizure: brain metastases

Differential DiagnosisDifferential Diagnosis

•Metastasis Metastasis from prostate, from prostate, lung, or lung, or melanoma.melanoma.

•EpididymitisEpididymitis

•LymphomaLymphoma

•SpermatoceleSpermatocele

•TB, gummaTB, gumma

•LeukemiaLeukemia

DiagnosticDiagnostic• Goal: Highly curable (85% of cases)Goal: Highly curable (85% of cases)

• Physical ExamPhysical Exam

• U/S: detects parenchymal U/S: detects parenchymal abnormalityabnormality

• CT CT abdomen, chest, pelvisabdomen, chest, pelvis: extent of : extent of disseminationdissemination

• MRI: Used when results don’t match MRI: Used when results don’t match or brain if pt. has CNS sx.or brain if pt. has CNS sx.

Labs: Tumor MarkersLabs: Tumor Markers

Alpha fetoprotein (aFP)Alpha fetoprotein (aFP)• half-life 5-7 dayshalf-life 5-7 days• commonly excreted by embryonal and yolk saccommonly excreted by embryonal and yolk sac• Indicates nonseminomaIndicates nonseminoma

Human Chorionic Gonadotropin Human Chorionic Gonadotropin (bHCG) (bHCG)

• Half-life 24hrsHalf-life 24hrs• Enhanced estrogen production of testes-Enhanced estrogen production of testes-

GynecomastaGynecomasta• Modestly elevated in pure seminomasModestly elevated in pure seminomas

Tumor MarkersTumor Markers

Lactate Dehydrogenase (LDH)Lactate Dehydrogenase (LDH)• Nonspecific tumor marker but is a useful Nonspecific tumor marker but is a useful

prognostic indicatorprognostic indicator

• Indicator of tumor burden Indicator of tumor burden

Primary Testicular CancerPrimary Testicular CancerGERM CELL (95%)GERM CELL (95%)

• Single cell-type 60%Single cell-type 60%

• Mixed 40%Mixed 40%

NONGERM CELL (5%)NONGERM CELL (5%)

• Leydig 1-3%Leydig 1-3%

• Sertoli <1%Sertoli <1%

• Gonadoblastoma Gonadoblastoma 0.5%0.5%

GCT 2 MAIN TYPESGCT 2 MAIN TYPES

1.1. Seminoma (40-50%) Seminoma (40-50%) Primoridal germ cellPrimoridal germ cell

2.2. Nonseminomas (50-Nonseminomas (50-60%)60%)

Embryonal cell Embryonal cell

Yolk sacYolk sac

TeratomasTeratomas

ChorlocarcinomasChorlocarcinomas

TherapyTherapy

• Seminomas are highly sensitive to XRTSeminomas are highly sensitive to XRT

• Tumors with seminoma histology with Tumors with seminoma histology with elevated AFP treat as nonseminomaelevated AFP treat as nonseminoma

• Brain metastasis should receive WBRBrain metastasis should receive WBR

• U/S testes shows malignancy, check U/S testes shows malignancy, check lab markers and proceed lab markers and proceed w/orchiectomy. w/orchiectomy.

• Exception: BenignException: Benign

Radical OrchiectomyRadical Orchiectomy

• Inguinal approachInguinal approach

• Testicle and Testicle and spermatic cord are spermatic cord are then sent to a then sent to a pathologist for pathologist for staging.staging.

StagingStaging

II Confined to testiclesConfined to testicles

IIIIMetastases to Metastases to retroperitoneal nodes; retroperitoneal nodes; sometimes catergorized as sometimes catergorized as nonbulky or bulky nonbulky or bulky dependant on size and dependant on size and number of nodes involvednumber of nodes involved

IIIIIIMetastases above the Metastases above the diaphragm or to visceral diaphragm or to visceral organs organs

Abnormal tumor marker Abnormal tumor marker levelslevels

AFP value of greater than 9 ng/mL is AFP value of greater than 9 ng/mL is considered abnormal.considered abnormal.

HCG level of greater than 4 mIU/mL is HCG level of greater than 4 mIU/mL is considered abnormal.considered abnormal.

LDH value of more than 1.5 times the LDH value of more than 1.5 times the reference range is considered abnormal.reference range is considered abnormal.

Tumor MarkersTumor Markers

• Serum tumor markers are routinely used Serum tumor markers are routinely used for diagnosis, staging and follow-up. for diagnosis, staging and follow-up.

• Absence of elevated levels of HCG, AFP Absence of elevated levels of HCG, AFP and LDH in a patient with a testicular mass and LDH in a patient with a testicular mass does not rule out the presence of a tumor. does not rule out the presence of a tumor.

• These markers can signal an incomplete These markers can signal an incomplete cure or relapse long before it is evidenced cure or relapse long before it is evidenced by physical or radiologic examination. by physical or radiologic examination.

PrognosisPrognosis

Seminoma Seminoma (at 5 years)(at 5 years)

• I: 98% I: 98%

• IIA: 92-94%IIA: 92-94%

• IIB-III: 33-75%IIB-III: 33-75%

NSGTNSGT (at 5 years) (at 5 years)

• I: 96-100%I: 96-100%

• IIA: >90%IIA: >90%

• IIB-III: 55-80%IIB-III: 55-80%

Stage IStage I Seminoma Seminoma

NonseminoNonseminoma ma

•XRT to XRT to retroperitoneal/ retroperitoneal/ inguinal nodesinguinal nodes

•RPLND or RPLND or surveillance surveillance

Stage Stage IIA(nonIIA(nonbbulky)bbulky)

Seminoma Seminoma

NonseminoNonseminoma ma

•XRTXRT

•RPLND +/- chemoRPLND +/- chemo

Stage Stage IIBIIB

(bulky)(bulky)

Seminoma Seminoma NonseminoNonseminoma ma

•XRT or chemoXRT or chemo

•chemo followed by chemo followed by resectionresection

Stage Stage IIIIII

Seminoma Seminoma NonseminoNonseminoma ma

•Chemo +/- resection Chemo +/- resection of residual mass of residual mass

Treatment OverviewTreatment Overview

retroperitoneal lymph node retroperitoneal lymph node dissectiondissection

• RPLND primary treatment (NSGCTs) RPLND primary treatment (NSGCTs)

• Remove abdominal lymph nodes Remove abdominal lymph nodes

• Problems mainly occur with the Problems mainly occur with the nerve: infertility, ejaculation nerve: infertility, ejaculation problemsproblems

ChemotherapyChemotherapy

BEP: (Bleomycin, Etoposide, Cisplatin) BEP: (Bleomycin, Etoposide, Cisplatin) 2-4 cycles 21d intervals (4 most 2-4 cycles 21d intervals (4 most common)common)

EP: (Etoposide, Platinol) 4 cycles 21d EP: (Etoposide, Platinol) 4 cycles 21d intervalsintervals

Salvage ThearpySalvage Thearpy

• No initial complete responseNo initial complete response

• VIP: (Etoposide, Ifosamide,Mesna, VIP: (Etoposide, Ifosamide,Mesna, Platinol) 3-4 cycles 21d intervalsPlatinol) 3-4 cycles 21d intervals

• High-dose chemotherapy with High-dose chemotherapy with autologous bone marrow autologous bone marrow transplantation in selected patients transplantation in selected patients with bulky disease with bulky disease

Follow upFollow up– physical examinations, chest physical examinations, chest

radiographs and serum tumor markersradiographs and serum tumor markers– CT scans detect recurrence in the CT scans detect recurrence in the

retroperitoneum and chest retroperitoneum and chest – Follow-up protocols vary by institution, Follow-up protocols vary by institution,

type, stage and treatment type, stage and treatment

Recommended ExamsRecommended Exams

• Every 2-3 months 1Every 2-3 months 1stst yr. yr.

• Every 3-6 month 2Every 3-6 month 2ndnd yr. yr.

• Every 6 month remainder 5 yrs.Every 6 month remainder 5 yrs.

• CTscans: 3-6 months 1CTscans: 3-6 months 1stst yr. then yr. then annuallyannually

• Men at high risk: Annually with self-Men at high risk: Annually with self-exam monthlyexam monthly

ComplicationsComplications

• Pulmonary toxicity: Bleomycin keep Pulmonary toxicity: Bleomycin keep total dose under 400 units.total dose under 400 units.

• Nephrotoxicity: Cisplatin- decreased Nephrotoxicity: Cisplatin- decreased Cr: Dosed based on CrClCr: Dosed based on CrCl

• Neurologic: Cisplatin- OtotoxicityNeurologic: Cisplatin- Ototoxicity• Cardiovascular: HTN, MI, AnginaCardiovascular: HTN, MI, Angina• Secondary Malignancies: Etoposide Secondary Malignancies: Etoposide

characterized by 11q23 translocationcharacterized by 11q23 translocation