sc urologia italian germ-cell cancer study group controversies in treatment and surveillance of...

Sc Urologia

Italian Germ-cell cancer Study Group

Controversies in treatment and surveillance of clinical stage I seminoma and nonseminoma testis cancerNicola Nicolai, Milan

Highlights in the Management ofUrogenital CancerRome, May 9-10, 2008

Mediterranean School of Oncology

Background

• Germ-cell tumors (GCTs) are rare, 1% only of solid tumors

• Age of onset (20-40 yrs old) is critical

• Highly curable neoplasms: almost 90% of patients are cured

Low-stage GCTs

• There is no Consensus concerning low-stages (stage and therapy)

• In contrast with what we have reached in advanced disease (IGCCCG, 1997)

Low-stage GCTs (2)

• Prognosis is not the main issue of low-stage disease

• In fact, the global outcome is extraordinarily favorable as nearly 98-99% of low-stages patients are cured

• QoL is the main issue

• QoL depends on: early and late toxicity of treatment and critical age of patients

Non-seminoma stage I

Staging and Therapy

Clinical stage I NS: common landmarks

• Definition No evidence of disease beyond the testis (normal t/2 markers decay following orchiectomy, normal imaging, as recent as possible)

• Cure-rate: 98-99%• 50 - 70% of NS are diagnosed at this stage:

treatment at this stage is crucial for the best global outcome (cure & morbidity) in most patients

• Risk factors: vascular invasion (VI), %ECa, others

Medical Research Council Model (the only validated

predictive model)

• Risk factors: venous invasion, lymphatic invasion, no YST, presence of ECa

• ≥ 3 factors high risk: 20% of patients,50% of them bearing occult metastases

• < 3 factors low risk: 80% of patients, 20% of them bearing occult metastases

European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Metting of the

European Germ Cell Cancer Consensus Group (EGCCCG). Eur Urol 2008;53:497

• Algorithm after orchiectomy for stage I NS• Low-risk (no VI) standard: surveillance

alternative: 2 PEBRPLND

• High-risk (VI) standard: 2 PEB alternative: surveillance

RPLND

2587 pts

VI OR 5.2

Availability of Vascular Invasion information (Nicolai et Al, J Urol 2004)

No. VI (%) Absent 131 (41) Present 72 (22) Not available 119 (37)

Reliability of VI information: Local (L) Vs Central Pathology (P) (Sesterhenn et Al, J Clin

Oncol, 1992)

Central pathology review

Absent Present Total

LP diagn.

Absent 201 135 336

Present 16 38 54

Unknown 18 6 24

Total 235 179 414

~30%

~40%

Reliability of VI information: Local (L) Vs Central Pathology (P) Fondazione INT, AUA

Proc 2008)

Central pathology review

Absent Present Total

LP diagn.

Absent 24 7 31

Present 5 28 33

Unknown 55 19 74

Total 84 54 138

~15%

~23%

~56%

Vascular Invasion (as it is!)

• Many reports (nearly 50%) do not contain this information

• There is a discrepancy of about 20% between first diagnosis and central review

• If this information is not reported and possibly reviewed, up to 70% of patients are randomly or wrongly treated in respect of the main prognostic factor!

Decision Making by issues

• Ease of use of therapy (single shot therapy)

• Complexity of administration

• Simplification of follow-up

• Late relapses

• Early and late toxicities

Active surveillance

RPLND

Chemotherapy

Orchiectomy “only” Intensified Observation: 30% chemotherapy and also surgery in 15-20% of cases.

4 wks of loss of time (hospital stay and convalescence)Further therapy in case of relapse in 10-15% of cases

5 wks of loss time (administration and recovery)Further therapy in 2-3% of cases

Ease of use of therapy

Adj ChT ≥ RPLND ≥ surv?

DISTRIBUTION OF NODAL METASTASIS IN NSGTCJ.P.Donohue J.Urol., 1982

12%88%

8%

4% 4%0%

0% 0%

4%40% 23%

0%

14%

0%

14%0%

7%

29%

71%79%

14%

0%

Right tumor Left tumor

Sympathetic retroperitoneal chain

Full bilateral (infra-hilar) nerve sparing RPLND

Modified bilateral RPLND for right tumor

Modified bilateral RPLND for left tumor

Post-chemotherapy (PC) RPLND and ejaculation

• Coogan et Al (Indiana Univ) J Urol, 156: 1656, 1996

• preservation of normal ejaculation in 76.5% of 81 patients undergoing nerve sparing PC RPLND

Active surveillance

RPLND

Chemioterapia

High compliancecompliance, (due to experience and ability of clinicians in administering proper information and confidence)

Does not avoid retroperitoneal surgery high surgical experience in order to keep antegrade ejaculation in patients submitted to post-Cht RPLND

High specialisation

Best results achieved in high volume centres

Proper knowledge is requested to plan an adjuvant treatment

A sophisticated competence to administer 2 courses of PEB is not needed (!)

Complexity Adj ChT > Surv > > RPLND?





• Late relapses


Follow-up: NS

• No consensus exists

• Schedules tend to be less intensive in case of active treatment

• Follow-up schedule is the treatment when active surveillance is chosen

• Different schedules may give different results

Sites of relapses following active surveillance

(from Stephenson & Sheinfeld Curr Treat Options Oncol, 2005)

Results of surveillance studies (Segal Uro Oncol: Seminars and Original Invest 2006 68–74)

Treatment Surveillance 1981-84: 85 pts

RPLND 1985-95: 322 pts

Tot N/M + 25 (29,4%) 89 (27,6%)

N+/pN+ only 11 (12,9%) 40 (12,4%)

N+/pN+ & M+ 3 (3,5%) 20 (6,2%)

M+ only 11 (12,9%) 43 (13,4%)

Late relapses 4/85 (4,7%)

4/25 (16%)

3/322 (0,9%)

3/49 (6,1%)

DSS 96,5% 98,8%

DOD/DWD 3 (2 RP) 4 (all lung mets)

Active surveillance Vs RPLND: INT experience

RPLND: therapeutic role

31/44 pN+ M0: 70.5% Nicolai et Al, J Urol, 2004

Adjuvant Chemo in CS I NS (from Stephenson & Sheinfeld Curr Treat Options Oncol,

2005)Study #pts Median f-

u, moRelapse

(%)RP

relapse (%)

DOD (%) DDT (%)

Oliver et Al, 2004

148 33 6 (4) NR 2 (1.4)

Cullen et Al, 1996

114 48 2 (1.7) 2 (100) 0 1 (.8)

Amato et Al, 2004

68 38 1 (1.5) 1 (100) 0

Bohlen et Al, 1999

59 93 2 (3) 2 (100) 2 (1.5)

Pont et Al, 1996

29 79 2 (7) 2 (100) 1 (3.5)

Teratoma in RP lymph-nodes following primary RPLND (from Carver & Sheinfeld Nat

Clin Practice Urol, 2005)

One Course of adjuvant PEB Vs RPLND in patients with stage I NSGCTT: results of the

German Prospective Multicentric Trial (Albers et Al, ASCO proc 2006)

• 1996-2005: 382 pts ® 1 PEB Vs RPLND• PS II at RPLND 2 PEB • 346 valuable: 172 RPLND, 174 PEB• Median F-U: 47 mos (93% with 1 yr of minimum f-u)• 13 (8%) relapses among RPLNDs* (3 in RP, 3

markers elevation, 2 inguino-scrotal relapses)• 2 (1%) relapses among PEBs (1 MT in RP, 1

markers elevation)* 15 recurrences in updated series presented at 2008 EAU

conference (Milan, March 2008)

Late Relapses (LR) (Geldart et Al, Brit J Urol 98, 2006)

• 1980-2004: 742 NSGCT of the testis• 405 Metastatic disease• 329 CRs (101 or 31% needed surgery too)• 18 early relapses• 20 LR, median time 108 (26–217) mos (≈ 9 years)• 15 surgery alone 14 NED at 44 (9-184) mos• 5 chemotherapy 1 NED

Active surveillance

RPLND

Chemotherapy

30% of relapses

Following 2° yr yet (16% of relapses in INT series)

8-14% of relapses (with and with no adjuvant chemotherapy)

< 1% following 2° yr ( less intensive follow-up)

Abdominal relapses rare (1-2%) (less TC!)

2-3% of relapses

Late relapses are possible and not yet explored

Follow-up Ad ChT = RPLND >> surv?

Active surveillance

RPLND

Chemotherapy

Late relapses have been reported, usually abdominal and large masses.

<1% in different series.

Surgery is the key-therapy for these relapses (early surgery means prevention)

2-3% relapse-rate.

Almost all are retroperitoneal: from half to all of these pts will not be cured.

Chemoresistant o chemo-insensitive disease (teratoma) in retroperitoneum.

Follow-up period not enough to valuate the occurrence of late relapses.

Late relapses RPLND >> Adj ChT > Surv?





• Late relapses


primary RPLND morbidityI.N.T.

Milano1

Indiana University2

German Study Group3

Loss of AE 1% if unilat

< 4% if bil

2% if NS 6,7%

Re-intervention

<1% <1% <1%

Mortality 0 0,2% 0

Abdominal recurrences

1,8%infield 0,3%?

1,1%infield 0%

1,3%infield 0,8%

1 unpublished2 Donohue et Al J Urol, 19933 Heidenreich et Al J Urol, 2003

CardioVascular Events (CVE)

• Huddart et Al, J Clin Oncol 2003

• 68/992 (6.9%) CVE among pts treated for GCTC (1982-92) after a median follow-up of 10.2 yrs

Cardiovascular events (Huddart et Al, JCO, 2003)

Second cancers • Travis et Al, J Nat Cancer Inst 97:1354, 2005• 14 tumor registries northam/eur 1943-01• 40576 pts with testis ca &1 yr of min survival• 2285 second solid cancers• RR 2.0 following RT• RR 1.8 following ChT• RR 2.9 following both RT & ChT• RR tends to decrease for non-seminomas

which were treated since1975

Second cancers

Travis et Al, J Nat Cancer Inst 97:1354, 2005

Active surveillance

RPLND

Chemotherapy

Intensive observation anxiety. Full dose chemotherapy for relapsed pts risk of cardiovascular disease and 2° cancer. Greater risk of loss of AE among pts who relapsed and submitted to post-ChT RPLND (2/3)

Avoids chemotherapy in 90% of pN0 patients and in 70% of pN+ patients.Loss of antegrade ejaculation < 2% in “high volume” centres

Toxicity may be severe also following just 1-2 cycles of ChT. Hypothetical risk of cardiovascular disease (2° cancer?).

Toxicity RPLND > Surv ≥ Adj ChT?

Decision analysis by issues




• Late relapses• Early and late

toxicities

• Cht ≥ RPLND ≥ Surv

• Cht > Surv >> RPLND

• Cht = RPLND >> Surv

• RPLND >> Cht > Surv• RPLND >> Surv ≥ Cht

Clinician-oriented Decision

Patient-oriented Decision

Laparoscopic retroperitoneal lymph-node dissection

Lap-RPLND

Lap-RPLND in testis cancer

• Possible applications– As staging and therapeutic procedure (primary or

post-ChT)

• Advantages– Less invasive than open RPLND

• Criticisms– Is it curative? In case of nodal metastasis at staging,

adjuvant chemo is required (more chemotherapy)– Is it cost-effective?

Risk adpted RPLND (open Vs Lap)

Risk factors for pN+ (Nicolai et Al, J Urol 2004)

• # pts: 322• Considered factors: V+

%ECa > 90%• Risk assignement: high ≥ 1 factor

low no factor

• Risk Categories :“low-risk” for pN+ (<14%)

“high risk” for pN+ (35%)

“Oncologic efficacy of laparoscopic RPLND in treatment of clinical stage I nonseminomatous germ cell testicular cancer.” Nielsen ME et Al Urology 2007.

Clinical stage I No 120 Post-RPLND Rx

Relapses Site of relapse

Pathologic stage I

74 (62%) 74 surveillance 7 (9%) 4 chest

2 pelvic1

1 biochemical

Pathologic stage II

46 (38%) 36 (78%) 2-3 PEB (3-4 wks within)

0

10 (22%) surveillance

2 (20%) 1 chest

1 biochemical

Template unilateral dissection behind lumbar vessels1outside surgical boundaries

“Quality of life after lap and open RPLND in clinical stage I nonseminomatous germ cell tumor: a comparison study”. Poulakis V et Al, Urology 2006;68:154.

test Lap-RPLND

# 21

Open-RPLND

# 29

Statistical significance

Visual analogue pain score

Baseline 0.8 (±0.3)1 mo 3.0

(±4.9)

6 mos 1.1 (±2.0)

1.1 (± 0.4)

5.2 (±4.6)

3.2 (±3.2)

NS

< .001

Overall disturbance by pain

Baseline 0.9 (±0.8)1 mo 3.4

(±4.5)

6 mos 1.2 (±2.1)

1.0 (±0.7)

5.3 (±4.1)

3.4 (±2.9)

NS

< .001

SF-36

Questionnaire

Physical functioning, social functioning, roles physical restrictions, bodily pain, general health, vitality

Significantly better in 6/6 domains

EORTC QLC-C30 questionnaire

Physical functioning, role functioning, emotional functioning, social functioning, global QoL, fatigue, pain

Significantly better in 7/7 domains

Lap-RPLND• Albqami & Janetschek, J Endourol 19 (6):683, 2005• 2001-4: 103 CS-I pts (further 59 with CS II disease)• median fu: 62 mos (6-113)• Technique: lap-dissection of tissue ventral to lumbars

vessels plan• 3 conversions (2.9%) to open procedure• 4 minor complications• Median ot 217 min; blood loss 144 ml, mean hospital stay

3.6 days• 26 pN+ adjuvant chemo no relapse• 77 pN0 observation 93.5% MFS & 5 relapses 1 RP, 3

lung, 1 markers only chemo 100% NED• Antegrade ejaculation preserved in 100% of 100

evaluable patients

Lap-RPLND• One surgeon INT experience• 2002-7: 43 “low-risk” CS-I pts• current technique: lap-dissection of tissue as in open

procedure• 3 conversions (7%) to open procedure (1st one)• 3 complications controlled without conversion• mean ot 203 min; median hospital stay 4 days• 3 pN+ 2 adjuvant chemo no relapse

1 surveilled super-hilar relapse• 40 pN0 observation 97.5% MFS & 1 relapse: 1 RP

PEB x 3 100% NED• Antegrade ejaculation preserved in 100% of evaluable

patients

Lap-RPLND

Advantages DisadvantagesLower morbidity

shortens (half) hospital stay

reduces convalescence period

reduces social costs

mantained AE

Staging role

Therapeutic role(?) good evidence

Cool

Technical demanding procedure

Only diagnostic (?)

Tends to increase ChT (if unselected pts)

Cool

Seminoma Stage I

Staging and Therapy

European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Metting of the

European Germ Cell Cancer Consensus Group (EGCCCG). Eur Urol 2008;53:497

• Algorithm after orchiectomy for stage I S standard: surveillance

alternative: 1 Carboplatin AUC 7

Radiotherapy PAS 20 Gy

Clinical Stage I Seminoma

• About 15-20% of untreated patients will relapse (usually in the retroperitoneum)

• For more than half a century, RT has been represented the standard treatment

• Traditional adjuvant therapy (PA and iliac RT Dog Leg at 25-30 Gy) reduced to less than 5% occurrence of relapses

Early stage seminoma

• 75-90% of seminomas are diagnosed when at clinical stage I

• Definition: as for Clinical Stage I non-seminoma

• An elevation of AFP is not consistent with a diagnosis of seminoma

Morbidity e 2° cancers

• Early Tox: GI, hematological • Fertility (1 yr to be reversible)• Cardiovascular: 2.3 HR for hearth death (infra- and

super-diaphragmatic RT; but still significant also for infradiaphragmatic RT (T 10-11)

• Hodgkin L, RCC, bladder, and gastric ca. (not significant increase following infra-diaphragmatic RT)

Hanks et Al, Int J Radiat Oncol Biol Phys, 24:913 1992Dieckamm et Al, Oncology, 51:450, 1994Ruther et Al, Oncology, 58:75, 2000Huddart et Al JCO, 21:1513 2003Zagars et Al, JCO, 22:640 2004Travis et Al, J Nat Cancer Inst 97:1354, 2005

Second Cancers in pts with testis neoplasm (S & NS) who survive > 10 yrs

(from Duchesne G, ASCO GU meeting 2008*)

Tumor (solid) RR (95% CI)

Lung 1.5 (1.2-1.7)

Esophagus 1.7 (1.0-2.6)

Colon 2.0 (1.7-2.5)

Bladder 2.7 (2.2-3.1)

Mesothelioma 3.4 (1.7-5.9)

Pancreas 3.6 (2.8-4.6)

Stomach 4.0 (3.2-4.8)

Connective Tissue 4.0 (2.3-6.3)

*derived from Travis LB et Al, J Natl Cancer Inst 2005;97:1354

Clinical practice change in the last 10 years

• The majority (56%) of canadian practitioners in 2001recommended RT as the best option for stage I seminoma

• By 2006, the majority favors active surveillance

• In UK, a single cycle of Carboplatin is now the most frequently offered treatment modality

(Huddart Clin Oncol (R Coll Radiol) 2006;18:693)

Clinical Stage I Seminoma

• Opportunity of cure for relapsed patients and late effects of radiation lead to new perspectives:

• Omission of therapy following orchiectomy• Modification of RT administration• Adjuvant Chemotherapy

Results of surveillance in stage I seminoma(from Warde PR, ASCO GU meeting, 2008)

Series # pts Median Follow-up

# relapses (%)

% Cancer Specific Survival

Germa Lluch et Al 45 34 5 (11) 100

Horwich et Al 103 62 17 (17) 100

Oliver et Al 67 61 16 (24) 97Ramakrishnan et Al 72 44 13 (18) 100

Daugaard et Al 394 60 69 (18) 100

Warde et Al 421 98 64 (15) 99.7

Active Surveillance

• Warde et Al (JCO, ’02), multicentric study

• 638 pts

• 19% of relapses after a median f-u of 7 yrs

• 69% within 2 yrs

• 7% after 6 yrs

• 5yr-OS: 98%

Clinical Stage I Seminoma: risk factors

• T size (≤ 4 Vs > 4 cm) and rete testis invasion are independent factors at multivariable analysis

• 5-year relapse rate as follows:• both factors (only 15% of pts) 31.5%• only one factor 15.9%• no factor 12.2%• 6.6% of relapses occurring more than 6 yrs after

orchiectomy

Warde P et al JCO 20:4448, 2002

Clinical Stage I Seminoma: risk adapted treatment

• 314 pts btw 1999 and 2003• 100 (31.4%) no risk factors surveillance• 131 (41.7%) T > 4 cm |• 33 (10.5%) rete testis invaded |Carbo x 2• 50 (15.9%) both factors |• 7.9% G 3-4 hematological toxicity• F-U of 12 to 72 months • 6 (6%) relapses among pts on surveillance• 7 (3.3%) relapses among treated pts• All rescued by EP

Aparicio J et al JCO 2005;23(43):8566

Evolution of Rx in Clinical Stage I Seminoma: MRC trials

• MRC TE 10 dog leg (DL) Vs para-aortic strip (PAS)

RT

• MRC TE 18 30 Gy Vs 20 Gy(EORTC 30942)

• MRC TE 19 RT (20/30 Gy) Vs single (EORTC 30982) dose Carboplatin

Fossa et Al, JCO 17:1146, 1999

Jones et Al, JCO 23:1200, 2005

Oliver et Al, Lancet 366:293, 2005

MRC TE 10: PAS Vs DL RT• Fossa et Al, JCO 17:1146, 1999• 1989-93: 478 pts (PAS 236, DL 242)• median fu: 4.5 yr• 18 relapses (9 each arm: 4 pelvic in PAS arm)• 3yr rel-free survival: PAS 96% (95-99%)

DL 96.6% (94-99%)• 3 yr survival: PAS 99.3% (1 DOD)

DL 100%• Acute tox: PAS less

leukopenia/diarrhea/nausea/vomiting• 1st normal sperm count (in pts with pre-RT normal values):

PAS: 13 mos (12.5-13.5 mos)DL: 20 mos (12,5-30 mos)

MRC TE 18: 30 Vs 20 Gy• Jones et Al, JCO 23:1200, 2005• 1995-98: 625 pts (30 Gy: 313; 20 Gy: 312)• median fu: 61 mos• 21 relapses: 30/20 Gy: 10/11; Pelvic 6/3 (1/5 DL, 8/16 PAS)• 5yr rel-free survival: 30 Gy 97% (94.3-98.3%)

20 Gy 96.4% (93.5-98%)• DS survival: 30 Gy 1 AWD

20 Gy 1 DOD• severe/moderate lethargy: 30 Gy 20%

20 Gy 5% p<.001• unability to carry out normal work at 4 wks

30 Gy:46%20 Gy:28% p<.001

• second cancer: 6 non-germ cell cancers, all in 30 Gy group

MRC TE 19: Carboplatin Vs RT• Oliver et Al, Lancet 366:293, 2005• 1996-2001: 1477 pts (30Gy/20Gy RT: 904; 1 course Carbo AUC 7: 573)• median fu: 4 yrs• 65 relapses; RT/Carbo: 36/ 29; RP: 13% Vs 74%; Pelvic 31% Vs 0• 3yr rel-free survival: RT 95.9% (94.4-97.1%)

Carbo 94.8% (92.5-96.4%)• DS survival: 1 DOD following RT• Acute tox: thrombocytopenia G1-2 RT 2% Carbo 12%

“ G3-4 RT 0 Carbo 4% p<.0001dyspepsia RT 17% Carbo 8% p<.0001

• Moderate/ severe lethargy: RT 24%Carbo 7% p<.0001

• unability to carry out normal work at 4 wksRT: 38%Carbo: 19% p<.0001

• second cancer: 10 (RT) to 2 (carbo) new germ cell cancers

“Effect of radiotherapy volume and dose on secondary cancer risk in stage I testicular seminoma”.Zwahlen DR et Al, Int J Radiat Oncol Biol Phys, 2008;70:853• the secondary cancer risk (SCR) due to para-aortic (PA), dogleg field (DLF),

or extensive field (EF) radiotherapy (RT) at different dose levels for Stage I testicular seminoma

• organ equivalent dose concept with a linear, plateau, and linear-exponential dose-response model

• estimated cumulative SCR for a 75-year-old patient treated with PA-RT at age 35 was 23.3% (linear model), 20.9% (plateau model), and 20.8% (linear-exponential model) compared with 19.8% for the general population

• dependent on the model, PA-RT compared with DLF-RT reduced the SCR by 48-63% or 64-69% when normalized to EF-RT for PA-RT, the linear dose-response model predicted a decrease of 45% in the SCR, using 20 Gy instead of 30 Gy

• the SCR after PA-RT for Stage I seminoma is reduced by approximately one-half to two-thirds compared with DLF-RT; the SCR is expected to be equal or lower with 20 Gy than with 30 Gy

The long-term risks of adjuvant carboplatintreatment for stage I seminoma of the testis. Powles T et Al. Ann Oncol 2008;19:443

• 199 patients with clinical stage I seminoma• 1 or 2 cycles of adjuvant carboplatin as a single agent• follow-up: 0.1-20.1 years (median 9) • no excess mortality compared with the age and sex-

matched UK population with 95% confidence intervals (CIs) on their standardised mortality ratio (SMR) from 0.36 to 1.83

• no significant increase in death from circulatory disease (SMR 1.44; 95% CI 0.39–3.69) or in incidence of second cancers [standardised incidence ratio (SIR) 0.96; 95% CI 0.26–2.45])

RT: PAS Vs DL

Advantages DisadvantagesReduction of acute toxicity

Earlier recovery of fertility

Simplification of treatment

Increase of pelvic recurrences (right)?

Does a risk of late toxicities remain?

RT: 20 Gy Vs 30 Gy

Advantages DisadvantagesEarly physical recovery

Reduction 2° cancer (?)

Increase of recurrences (nonpelvic)?

Does a risk of late toxicities remain?

Carboplatin Vs RT

Advantages DisadvantagesReduction of GI tox Increase of hematological tox

Earlier physical recovery Increase of retroperitoneal relapses (?)

Reduction of 2° cancer risk (?) Too few data and too early for evaluation

Reduction contralateral cancer

THM

• Prognosis of stage I GCTs is excellent when proper treatments are administered

• Modern concepts must include consideration regarding ease of use and complexity of therapy, simplification of f-u, late relapses and toxicity (early and late)

THM: non seminoma

• 3 choices: surveillance, RPLND, adjuvant chemotherapy (2 PEB)

• Beware of VI! (possibly review)

• Consider availability of resources and patient preference

• Consider aspects favoring patients

THM: seminoma

• 3 choices: surveillance, adjuvant radiotherapy (PAS, 20 Gy), adjuvant chemotherapy (CBCDA 7 AUC)

• Data on CBCDA are too early to draw definitive conclusions on long term safety

• Consider availability of resources and patient preference

• Consider aspects favoring patients

Italian Germ-cell cancer study Group

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sc urologia italian germ-cell cancer study group controversies in treatment and surveillance of...

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