PATONE’S RAD‐ONC REVIEW NOTES 2008
TESTICULAR CANCER
Etiology/Epidemiology:
‐1‐2% of male cancers
‐Most common malignancy in men 15 ‐ 35yo
Risk Factors:
‐Major: testicular mal‐descent (RR 5x), contralateral testes tumor (5%), family hx of testes
cancer, gonadal dysgenesis
‐Minor: mumps orchitis, testicular trauma, immune deficiency (including HIV/AIDS)
‐Also: first‐born, pre/perinatal estrogen exposure, PVC exposure, advanced maternal age,
Down’s and Klinefelter’s syndrome
Screening: No evidence, suggest U/S of contralateral testicle from age 15 if prior hx.
Cytogenetic Findings:
‐12p isochromosome in 80% (K‐ras is located on 12p)
‐17q over‐represented in 50%
Histologic Classification:
‐Germ Cell Tumors:
‐Seminoma (classic: PLAP+ / spermatocytic: PLAP‐) (no AFP!)
‐Embryonal carcinoma
‐Choriocarinoma (↑β‐hCG)
‐Yolk sac tumor (endodermal sinus tumor) (↑AFP)
‐Sex Cord‐Stromal Tumors:
‐Leydig cell tumor (androgen & estrogen producing)
‐Sertoli cell tumor (estrogen producing)
‐Granulosa cell tumor
‐Mixed Tumors:
‐Gonadoblastoma
‐Adnexal & Paratesticular Tumors:
‐Mesothelioma
‐Miscellaneous Tumors:
‐Carcinoid
‐Lymphoma
‐Cyst
‐Metastatic Tumors
‐Broadly: Seminoma vs Non‐Seminoma (60% Pure Seminoma, 30% NSGCT, 10% mixed GCT)
‐Note: average age of presentation: Seminoma 36yo, NSGCT 27yo
‐Pure seminomas do not produce AFP!
TESTICULAR CANCER PAGE 1
PATONE’S RAD‐ONC REVIEW NOTES 2008
Pathway of Spread:
‐Left testicular vein drains into left renal vein i.e. must cover up to left renal hilum
‐Right testicular vein drains into IVC
Work Up:
‐AFP/β‐hCG/LDH prior to surgery
‐For staging: CT‐chest/abdo/pelvis Æ can avoid CT‐chest in seminoma without LN (CXR instead)
‐Bone scan if ≥Stage 2
‐Expected post‐op markers: β‐hCG half‐life = 24h, AFP = 5days, LDH = 9h
‐Do NOT forget to do fertility testing/sperm banking!
Staging:
pTX: Cannot be assessed
pTis: Intratubular germ cell neoplasia
pT1: Limited to testes/epididymis without LVI, invasion into tunica albuginea is allowed
pT2: Limited to testes/epididymis with LVI or invasion into tunica vaginalis
pT3: Spermatic cord involvement
pT4: Scrotal involvement
NX: Not assessed
N1: Single or multiple nodes all ≤2cm
N2: Single or multiple nodes at least one of which is >2cm and all ≤5cm
N3: Any node >5cm
Regional nodes are paraaortic, paracaval, retroaortic, retrocaval, interaortocaval
M1a: Non‐regional node involvement or lung metastasis
*External iliacs and inguinals cannot be considered regional unless there is
scrotal violation
M1b: Distant mets outside of nodes and lungs
S0: All serum markers WNL
S1: LDH <1.5xULN & β‐hCG <5000mIU/mL & AFP <1000ng/mL
S2: Intermediate
S3: Any of LDH >10xULN, β‐hCG >50,000, or AFP >10,000
Stage Grouping:
IA pT1
IB pT2‐4 N0M0S0
IS pT1‐4 N0M0S1‐3
IIA N1 S0‐1
IIB N2 S0‐1
IIC N3 S0‐1
IIIA M1a S0‐1
IIIB S2 & any N+ or M1a
IIIC S3 & any N+ or M1a, or M1b
TESTICULAR CANCER PAGE 2
PATONE’S RAD‐ONC REVIEW NOTES 2008
Royal Marsden Staging (Use this One!): 10y RFS (Seminoma): 10yOS:
I: Limited to testis I: 97%, >99%
IIA: Nodes <2cm IIA: 92% >98%
IIB: Nodes >2‐5cm IIB: 86% >95%
IIC: Nodes >5‐10cm IIC: 70% (RT alone) Æ >90% (w chemo) 90%
IID: Nodes >10cm IID: 50% (RT alone) Æ 90% (w chemo) 90%
III: Nodes above & below diaph III: 85%
IV: Extralymphatic mets IV: 80%
Treatment:
‐Surgery: must be radical inguinal orchiectomy. Scrotal violation thought to compromise
outcome but no definitive proof of this.
SEMINOMA
‐Stage Distribution: 80% Stage I, 15% Stage II, and 5% stage III
Stage I: Options:
‐Surveillance: 15% relapse, 100% survival
‐Adjuvant RT (para‐aortic, 25Gy/15#)
‐PMH: 345 pts, 10y f/u, 5y RFS 85% on surveillance vs 95% post‐RT
‐OS with salvage 100%
‐Data also from Danish Testicular Group
‐Predictors for Relapse (Warde):
‐LVSI: present ‐ 17%, absent ‐ 9%
‐Size: >4cm ‐ 15%, <4cm ‐ 10% (HR 2 for relapse)
‐Rete testis involvement (HR 1.7 for relapse)
‐Both >4cm and rete testis involvement (HR 3.4 for relapse)
‐Late relapses >4y can happen!
‐Salvage therapy:
‐Retroperitoneal RT (if <5cm) with rates of LRR after salvage in range of 10%
‐Chemo (if bulky or supradiaphragmatic relapse) leads to almost 100% cure
‐PMH data: no difference in the number of pts who required chemo b/w pts on
surveillance (5.1%) or pts who received RT (3.5%)
‐Protocol for surveillance:
‐2y: q4 mo CT‐abdo/pelvis, CXR, markers
‐3‐7y: q6 mo CT‐abdo/pelvis, CXR
‐8‐10y: q12 mo CT‐abdo/pelvis, CXR
TESTICULAR CANCER PAGE 3
PATONE’S RAD‐ONC REVIEW NOTES 2008
‐Other Alternatives:
‐RPLND, only if pt has contraindication to RT such as IBD
‐Chemo with single cycle of Carboplatin
‐MRC/UK (Oliver) trial published comparing RT to Carboplatin, 1477 pts
‐Follow‐up is only 4y long (see below)
Stage II:
‐Most important prognostic factor is bulk (5cm or greater)
‐Adjuvant RT (for non‐bulky disease Æ Stage IIA‐B):
‐PMH data, 5y LC 91% and OS 95% range
‐If >5cm LC drops to 44% mandating chemo as primary adjuvant
‐Other reasons to use chemo: location, horseshoe kidney, wide spread of nodes, etc.
‐Adjuvant Chemo (for bulky disease Æ Stage IIC‐D):
‐Use Etop‐Cisp (EP) +/‐ Bleo x3‐4 cycles (EP x4 or BEP x3), though BEP is no longer used…
‐Occasionally RPLND, but would not answer this as first choice
‐Also: combined adjuvant chemo and RT is investigational, small reports may favor
‐Management of residual mass post‐RT or post‐chemo:
‐Observation vs surgical removal vs PET scanning (De Santis study)
‐MSKCC (Puc study) estimate of disease in residual mass >3cm is 30%, <3cm is 0%
‐Immediate RT for residual disease is not justified!
Stage III:
‐4 cycles of Etop‐Cisp (EP) results in 92% progression free survival at MSKCC
NON‐SEMINOMA GCT (RT NOT USED!)
Stage I:
‐Surveillance (30% relapse rate), or
‐RPLND (10% relapse rate), or
‐BEP x2 (2% relapse rate)
‐Predictors for relapse: T4, LVSI, presence of embryonal carcinoma, or absence of yolk sac
‐If 3 or more risk factors, relapse rates approach 60%
‐OS is excellent (~100%) with rare deaths from disease
Stage II:
‐Non‐Bulky (<5cm):
‐RPLND (10‐40% relapse rate)
ÆIf after RPLND Æ >6 nodes +ve or non‐compliant patient with >2cm Æ add chemo
‐Adjuvant chemo 4x EP (shows no relapses with 3y f/u)
‐Bulky (>5cm):
‐Adjuvant chemo EP x4 (or BEP x3)
TESTICULAR CANCER PAGE 4
PATONE’S RAD‐ONC REVIEW NOTES 2008
Stage III:
‐Treat with chemo EP x4 (or BEP x3)
‐Good Prognosis: (testis/RP primary, no visceral mets, AFP <1000, β‐hCG <5000, LDH <1.5 xULN)
‐5yOS 92%
‐Intermediate Prognosis: (testis/RP primary, no visceral mets, intermediate lab values)
‐5yOS 80%
‐Poor Prognosis: (mediastinal primary, nonpulm visceral mets, or AFP >10,000, β‐hCG >50,000,
LDH >10 xULN)
‐5yOS 48%
‐Data from MRC‐UK/MSKCC/Indiana University
‐BEP is better then BE‐Carbo (97% vs 90% according to MRC/EORTC trial at 3y)
‐Standard of care is BEP x3 or EP x4, also in use is VIP (Etop, Ifos, Cisp)
‐Stem cell transplant (no data supporting a benefit as of yet, investigational)
Special Tumor Types:
‐Leydig Cell: Rare, no role for standard adjunctive RT or chemo. RPLND is a good option.
‐Sertoli Cell: Orchiectomy is almost always curative (benign course)
‐Extragonadal Germ Cell Tumors: Seminomas 90% cure, NSGCT 50% (Use chemo!)
Special Treatment Situations:
‐Horseshoe kidney: Send for RPLND
‐Immunosuppressed patients: Treat as standard
‐Brain metastasis: can have 50% 5yOS – choose therapy wisely
‐For isolated metastasis, consider giving whole brain RT (40Gy/20#) plus SRS techniques
to boost additional 10‐15Gy
Important RT Studies:
‐MRC trial (478 pts) compared dogleg vs paraaortic RT in Stage I with no difference in 3yOS/RFS
rates and no difference in recurrence rates but fractionally more recurred in pelvis in PA arm:
‐3y pelvic RFS 100% (dogleg) vs 98% (paraaortic)
‐MRC TE18 trial compared 30Gy/15# vs 20Gy/10# showed equivalent relapse rate (however one
pt relapsed in‐field with 20Gy/10# and should be regarded with caution)
‐5y RFS 97% (30Gy) vs 96.4% (20Gy)
‐MRC trial (Oliver) with 1477 Stage I pts compared paraaortic RT (20‐30Gy) vs Carbo x1 cycle
‐Equivalent 4y RFS 96% vs 95%
‐Relapse sites: Carboplatin = 70% PA, 4% pelvic
‐Relapse sites: RT = 7% PA, 28% pelvic
‐Only 4y f/u, so who knows how these pts will do long‐term!
TESTICULAR CANCER PAGE 5
PATONE’S RAD‐ONC REVIEW NOTES 2008
RT Field Setup:
‐Simulation:
‐Position: Supine, with arms on the side
‐Immobilization: Vac‐lock, knee rest
‐Testicular shielding with a clam shell
‐Reduces dose to remaining testicle (exact amount different in each book!)
‐CT scan with IV and 5 mm cuts
‐Volumes:
‐GTV = Gross tumor (usually nodal enlargement)
‐CTV = GTV + 1 cm + paraaortic LNs (+/‐ ipsilateral pelvic LNs for dogleg RT)
‐Include the left renal vein and hilum for left testicular tumors
‐PTV = 7 mm
‐Boost PTV = GTV + 7 mm
‐Standard Fields:
‐Supine, AP/PA, 18MV
‐PA RT: Extend from T10/11 junction to L5/S1
‐Dogleg RT: PA fields + extend inferiorly to top of ipsilateral obturator foramen
‐Key: Left side, cover the left renal hilum (EXAM question!)
‐Typically an 8cm field is used, widen left margin to 5cm and shape blocks around left
renal hilum if left sided tumor.
‐Supraclav irradiation is not justified Æ Use chemo instead if you are that concerned
‐Dose: PMH gives 25Gy/20#, but McGill uses the following:
‐Stage I: 25Gy/15#
‐Stage IIA: 25Gy + 5Gy boost = 30Gy/18#
‐Stage IIB: 25Gy + 10Gy boost = 35Gy/21#
‐Organs at Risk:
‐Small bowel <40Gy
‐Rectum <60Gy
‐Bladder <65Gy
‐Femoral heads <52Gy
‐Kidneys <23Gy to 2/3rds of one kidney
TESTICULAR CANCER PAGE 6
PATONE’S RAD‐ONC REVIEW NOTES 2008
‐Treatment Complications:
‐Acute: ‐Mild nausea and vomiting, diarrhea and GI discomfort
‐Fatigue
‐Azoospermia
‐50% of patients have impaired fertility before treatment
‐0.5Gy causes temporary azoospermia
‐1Gy causes total azoospermia
‐2Gy causes sterilization
‐Normalization of sperm count:
‐13 mo for paraaortic irradiation
‐20 mo for pelvic irradiation
‐No difference at 3y
‐Pts advised not to conceive for 6 mo after treatment
‐After RT, 30% of pts still able to have children
‐Late:
‐Second malignancy (non testicular tumors!):
‐Risk apparent 10 ‐ 15y after treatment
‐0.7% per year (16% at 25y and 23% at 30y)
‐Leukemia seen with RT or chemotherapy
‐Stomach, bladder and pancreas cancer seen with RT alone
‐Second malignancy risk (from Gunderson):
‐Travis data from NCIC‐ SEER Database Review:
‐Observed to Expected ratio at 25y was 1.43, actuarial risk was 16% at
25y and 23% at 30y
‐This is compared to actuarial risk of 9% for the general population
‐Of course this was based on more extended RT fields at use in that time
‐Reasonable to quote 2x doubling of baseline risk
‐Also, 2‐5% develop testicular tumors later in life!
‐Cardiovascular toxicity
‐Small bowel obstruction, chronic diarrhea, peptic ulcer disease (<2%)
‐Chemo: Do not forget typical early and late chemo toxicities!
‐Peripheral neuropathy due to Cisp
‐Nephrotoxicity due to Cisp
‐Ototoxicity due to Cisp
‐Pulmonary toxicity due to Bleo
‐Infertility due to Bleo (~40‐50%)
TESTICULAR CANCER PAGE 7
PATONE’S RAD‐ONC REVIEW NOTES 2008
Sample RT Planning Images:
Paraaortic Fields Dogleg Fields
TESTICULAR CANCER PAGE 8
PATONE’S RAD‐ONC REVIEW NOTES 2008
Summary: Seminoma * Do not forget Fertility Issues *
Stage Treatment
I Radical inguinal orchiectomy Æ
1. Surveillance (15% relapse rate) (↑ relapse if tumor >4cm, rete testis
involved, or LVSI)
2. RT (paraaortic, 25Gy/15#)
3. Carboplatin x1‐2 cycles (not standard option yet)
4. RPLND (if non‐RT candidate Æ also not standard, use chemo instead)
IIA‐B (<5cm) Radical inguinal orchiectomy Æ
1. RT (dogleg, 25Gy/15# + boost to 30Gy for IIA, or 35Gy for IIB)
2. Chemo (EP x4) for non‐RT candidate
IIC‐D (>5cm), & Radical inguinal orchiectomy Æ
III 1. Chemo (EP x4 or BEP x3)
5yOS:
I: >99% IIA/B: >98% III: 90% M+: 80‐85%
IIC/D: >95%
5y LR for untreated stage I pts depends on # risk factors: >4cm, rete testis involvement, or LVSI
# Factors: 5y LR:
0 10%
1 15%
2 30%
3 >30%
TESTICULAR CANCER PAGE 9
PATONE’S RAD‐ONC REVIEW NOTES 2008
Summary: NSGCT * Do not forget Fertility Issues *
Stage Treatment
I Radical inguinal orchiectomy Æ
1. Surveillance (30% relapse rate)
2. RPLND (10% relapse rate) – preferred for T4, LVSI & embryonal ca
3. BEP chemo x2 (2% relapse rate) is also a good option
IIA‐B (<5cm) Radical inguinal orchiectomy Æ
1. RPLND (10‐40% relapse rate)
Î Indications for additional chemo Æ >6 LNs or LNs >2cm on path
2. Chemo (EP x4 or BEP x3)
IIC‐D (>5cm), & Radical inguinal orchiectomy Æ
III 1. Chemo (EPx4 or BEP x3)
5yOS:
I: 95% IIA/B: 90% III good: 90%
IIC/D: 90% III intermed: 80%
III poor: 50%
TESTICULAR CANCER PAGE 10
