A Review of the Current Testis Cancer Continuum:
Patterns, Guidelines, Needs and Resources
Mike Craycraft R.Ph.Survivor/Founder
Testicular Cancer Society
Who Am I?
My First Year
Xavier University
(soccer)U.C. College of
Pharmacy
18 Years
Clinical Pharmacy/
Management
Testicular Cancer Society
Maddux Mustang Unicycle Team
LUMP
Oh No!
TESTICULAR CANCER
Upsetting
Others
Fear
Denial
“After V
ail
I’ll Go!”
“Pop’s 60th
Can’t Ruin His
Birthday”
“After A
spen
I’ll Go!”
St. Croix Luau
“I’m not going to make
it anyway”
“After Costa Rica I Have to Go!”
“Two separate nodules of seminoma, classic type,
limited to the testis.”
1%
http://seer.cancer.gov/statfacts/html/testis.html
8500
http://seer.cancer.gov/statfacts/html/testis.html
350http://seer.cancer.gov/statfacts/html/testis.html
1 GuyEvery HOUREvery DAY
} DIAGNOSED
1 GuyEvery DAY} DIES
1 in 250 Diagnosed
1 in 5000 Dies
Thanks to EARLY Diagnosis and Treatment
http://seer.cancer.gov/statfacts/html/testis.html
What Causes Testicular Cancer?
http://www.flickr.com/photos/mugley/
http://www.flickr.com/people/rubbertoe/
http://sammibugscrapshack.blogspot.com/
http://www.flickr.com/people/pinksherbet/
Risk Factors
No strong connections between certain lifestyles, habits or activities.
Undescended Testicle(s)
Abnormal Testicular Development
Family History
Many Guys have NO RISK FACTORS
Who Gets Testicular Cancer?
Anyone with A Testicle
15 35LEADING CAUSE
OCCURS AT ANY AGE
20 45HIGHEST RISK
http://seer.cancer.gov/statfacts/html/testis.html
http://seer.cancer.gov/statfacts/html/testis.html
Increasing Incidence
Andrology. 2014 Oct 20. doi: 10.1111/andr.288
Andrology. 2014 Oct 20. doi: 10.1111/andr.288
There are no studies that address the health benefits of attending a University of
Texas football game.
There are no studies that address the harms associated with attending a University of Texas football game.
Quiz
A. Current evidence is insufficient to assess the balance of benefits and harms of attending a University of Texas football game.
B. There is moderate or high certainty that attending a University of Texas football has no net benefit or that the harms outweigh the benefits.
IIf the service is offered, patients should
understand the uncertainty about the balance of benefits and harms.
DDiscourage the use of this service.
http://www.testicularcancersocietyblog.org/only-1-in-3-guys-know-how-to-check-their-testicles/
http://www.testicularcancersocietyblog.org/not-many-are-talking-about-testicular-cancer/
Testicular Self Exam
If you do notice
any lumps or
changesit is important to
see a doctor
immediately.
www.BallChecker.com
Signs and Symptoms of Testicular CancerEnlargement of a Testicle
Enlargement or tenderness in the breasts
Feeling of Heaviness in the Scrotum
Dull Ache in the lower abdomen, back or groin
Collection of fluid in the scrotum
Pain or discomfort in the testicle or scrotum
Loss of Size in one of the testicles
Difficulty Breathing
STAGES
Image from Urology Care Foundation
Image from Urology Care Foundation
Image from Urology Care Foundation
Stage I >99%
Stage II 96%
Stage III 73%
Survival Rates
http://seer.cancer.gov/statfacts/html/testis.html
Recent Reviews
TREATMENTS
ASCO Guidelines
[coming soon]
Types of Testicular Cancer
Seminoma
NonSeminoma
Focus on Clinical Stage I Testicular Cancer
J Clin Oncology Vol 32, No 4_suppl, 2014: abstract 369
Stage I
•Active Surveillance•Adjuvant Chemotherapy x 1 or 2 Doses•Adjuvant Radiation Therapy
Stage II
•Radiation Therapy•Chemotherapy x 3-4 Cycles
Stage
III
•Chemotherapy x 3-4 Cycles
SEMINOMA
Stage I
•Active Surveillance•Adjuvant Chemotherapy x 1 or 2 Cycles•RPLND
Stage II
•RPLND•Chemotherapy x 3-4 Cycles
Stage
III
•Chemotherapy x 3-4 Cycles
NONSEMINOMA
International Germ Cell Consensus Classification:a prognostic factor-based staging system
for metastatic germ cell cancers.
J Clin Oncol. 1997 Feb;15(2):594-603.
Percent ofGCTs
5-year Survival
Rate
Good Prognosis 60% 91%
Intermediate Prognosis
26% 79%
Poor Prognosis 14% 48%
Seminoma Risk Stratification
PrimaryTumor
MetastasisStatus
Tumor MarkerStatus
Low Risk Any No NonpulmonaryVisceral Metastasis
Normal AFPAny b-hCGAny LDH
Intermediate Risk
Any Nonpulmonary Visceral Metastasis
Normal APPAny b-hCGAny LDH
No Seminomas are considered High Risk
Nonseminoma Risk StratificationPrimaryTumor
MetastasisStatus
Tumor MarkerStatus
Low Risk Testis or Retroperitoneal
No NonpulmonaryVisceral
Metastasis
ALLAFP <1,000B-hCG <5,000LDH <1.5x ULN
Intermediate Risk
Testis or Retroperitoneal
No Nonpulmonary Visceral
Metastasis
ANYAFP 1,000 – 10,000B-hCG 5,000 – 50,000LDH 1.5x – 10x ULN
HighRisk
Testis or Retroperitoneal or Mediastinal
Mediastinal Primary or
Nonpulmonary Visceral
Metastasis
ANYAFP > 10,000B-hCG > 50,000LDH > 10x ULN
Treatment by Risk StratificationChemo
Regimen
Low Risk BEP x 3or
EP x 4
Intermediate Risk
BEP x 4or
VIP x 4
HighRisk
BEP x 4or
VIP x 4
Chemo Regimen
EP EtoposideCisplatin
BEP BleomycinEtoposideCisplatin
VIP EtoposideIfosfamideCisplatin
J Clin Oncology Vol 32, No 4_suppl, 2014: abstract 369
50.3% CS I LVI-
Nonseminoma hadAdjuvant Chemo
Barriers toActive Surveillance
Active surveillance doesn’t work in real-life situations.
Noncompliance leads to poor-prognosis at relapse
Frequent CT scans lead to radiation exposure and secondary malignancies.
J Clin Oncol. 2013 Oct 1;31(28):3490-3.
Cure Rates Approach
100%
Cancer. 2014 Oct 24. doi: 10.1002/cncr.29094.
Cancer. 2014 Oct 24. doi: 10.1002/cncr.29094.
NS NS
Clinical Stage I Seminoma
Option Outcomes Advantage Disadvantage
Active Surveillance 20% Relapse.
99% Long-term CSS
No treatments Relapse means higher doses of Radiation Therapy or Full-Dose Chemo w/ Residual Mass Management.
Adjuvant Radiation Therapy
4% Relapse.
99% Long-term CSS
Reduced relapses & need for Chemo & Freq. of Abd. Imaging
Short-term side effects & Long-term risk of Secondary Malignancy
Adjuvant Carboplatinx1 or x2 Doses
4% Relapse.
99% Long-term CSS
Reduced relapses & need for Chemo & Radiation.
Short-term side effects & Long-term risks unknown.
Who is going to relapse?
Clinical Stage I Seminoma
AgeTumor Size
Rete Testis InvasionVascular Invasion
Epididymis InvasionhCG Level
Tunica Albuginea Invasion
No Validated Prognostic Factors for Recurrence Exist
Clinical Stage I Seminoma
Eur Urol. 2014 Dec;66(6):1172-8.
1954 CSI Seminoma Patients on Surveillance(median follow-up time 15.1 years)
DSS at 5, 10 and 15 years99.6%, 99.4% and 99.3%
18.9% (n=369) Relapsed (median time of 13.7 months)
99.5% Good Prognosis Risk0.5% Intermediate Prognosis Risk
95.7% of Relapses were in 5 years4.3% of Relapses after 5 years
Clinical Stage I Seminoma
Eur Urol. 2014 Dec;66(6):1172-8.
Clinical Stage I Nonseminoma
Option Outcomes Advantage Disadvantage
Active Surveillance 30% Relapse.
15% Low-Risk Group
50% High-Risk Group
No treatments Relapse means Full-Dose Chemo w/ Residual Mass Management.
Retroperitoneal Lymph Node Dissection (RPLND)
20-30% Relapse. Reduced relapses & need for Chemo & Freq. of Abd. Imaging
Surgical Risks.
Adjuvant BEPx1 or x2 Cycles
1-5% Relapse. Reduced relapses & need for Chemo
Long-term Risks Unknown.
Lymphovascular Invasion
J Clin Oncol. 2013 Oct 1;31(28):3490-3.
J
J Clin Oncol. 2015 Jan 1;33(1):51-7.
99.7% 5- and 10-yearDisease Specific Survival
J Clin Oncol. 2015 Jan 1;33(1):51-7.
1344 CSI Seminoma Patients on Active Surveillance(median follow up 52 months)
13% Relapsed(median time to relapse was 14 months)
92% of Relapses were within 3 years(<1% of total population relapsed >3 years)
98.8% of Relapses were Good Prognosis1.2% of Relapses were Intermediate Prognosis
No Patients died from Seminoma1 Patient Died from Treatment-Related Complications
J Clin Oncol. 2015 Jan 1;33(1):51-7.
1139 CSI Nonseminoma Patients on Active Surveillance(median follow up 62 months)
19% Relapsed Overall44% LVI+ Relapsed14% LVI- Relapsed
38% LVI unknown Relapsed(median time to relapse was 6 months)
95% of Relapses were within 2 years
90%, 8% & 2% of Relapses were Good, Intermediate and Poor Prognosis Prognosis
3 Patients died from Nonseminoma2 Patient Died from Treatment-Related Complications 99.4% 5-yr DSS
J Clin Oncol. 2015 Jan 1;33(1):51-7.
NCCN = 6-9 CTs5-7 CTs
6-7 CTs
1226 CSI Nonseminoma Patients on Active Surveillance(median follow up 180 months)
30.6% 5-year Risk of Relapse(median time to relapse was 5 months)
94.4%, 4.7% & 0.8% of Relapses were Good, Intermediate and Poor Prognosis (2% unclassified)
6 Patients died from Nonseminoma4 Patient Died from Treatment-Related Complications 99.1% 15-yr DSS
Risk FactorsVI+, Rete Testis Invasion, Embryonal
26% PC-RPLND (8% total population)
J Clin Oncol. 2014 Dec 1;32(34):3817-23.
J Clin Oncol. 2014 Dec 1;32(34):3817-23.
Adjuvant Therapy
Adjuvant radiation therapy has fallen out of favor.
European Urology 67 (2015) 544–545
Carboplatin x1 or x2 Doses?
Stage I Seminoma
Stage I Nonseminoma
Adjuvant BEP x1 or x2 Cycles?
Relapses after Adjuvant BEP Chemo-Resistant?
517 patients, BEPx1, media follow up 7.9 years
2.4% Overall Relapse Rate3.2% Relapse LVI+1.6% Relapse LVI-
5- & 10-year CSS = 100% & 99.6%100% & 99.3% for LVI+100% & 100% for LVI-
Ann Oncol. 2014 Nov;25(11):2167-72
Quality of Care
“…quality of care currently improves survival at a higher rate than any possible new drug.”
Dr. Peter Albers
European Urology 67 (2015) 544–545
J Natl Cancer Inst. 1999 May 19;91(10):839-46.
J Natl Cancer Inst. 1999 May 19;91(10):839-46.
J Natl Cancer Inst. 1999 May 19;91(10):839-46.
J Clin Oncol. 2008 Jun 20;26(18):2966-72
7.937(95% CI, 1.808 to 34.48)
4% Retroperitoneal Relapse RateCommunity-based Study
1.2% Tertiary Referral Centers
J Clin Oncol 32:5s, 2014 (suppl; abstr 4519)
J Urol. 2015 Feb;193(2):507-12. J Urol. 2015 Feb;193(2):513-8.
BEP x3 vs EP x4?
IU says BEP is better MSK says EP is better
27% BEP vs 2% EP at IU Most BEP Outside MSK
Is this more about chemotherapy effectiveness or adherence to chemotherapy protocols and RPLND
referral patterns?
National Second-Opinion Project on Testicular Cancer
39.5% Discordancein 926 patients
Second-opinion Discordance28.1% Less Extensive15.6% More Extensive
56.3% No Difference in Scope
69% (462/668) applied 1st or 2nd Opinion85.3% Second vs. 14.7% First
31% Used Neither
Access to Care
European Urology 67 (2015) 544–545
J Urol. 2014;191(4):e90.
p<0.0001
J Urol. 2014;191(4):e90.
p=0.025
For Every 100 Young Men Insured
J Urol. 2014;191(4):e90.
6 Reduced Treatment Burdens
1Life
Saved
The Key to Testicular Cancer Careis Avoiding Pitfalls
Late Diagnosis
Misinterpretation of Pathology, Imaging & Tumor Markers
Mis-assignment of Stage & Risk Category
Misuse/Over use of Imaging, especially PET Scans
Inconsistent Delivery of Chemotherapy
Suboptimal RPLND due to using Non-open/Non-experts
Centralization of care and/or oversight of clinical decision making could be the solution.
Stage I Testis Cancer
Primum Non Nocere
Active Surveillance is a preferred approach
Patient-Centered ApproachEducating the patients to risks vs. benefits
Individualization based on Patient & Risk Aversion
Assessing Coping Ability & Level of DistressConsidering Life Disruptions by Relapse
Assessing Risk on Noncompliance & Access to Care
Patient-Centered Approach
SeminomaLeast Intervention = Active Surveillance but risk full chemo
Avoid Any Chemo = Adjuvant Radiation (esp. in older pts.)
Avoid Radiation = Active Surveillance or Adjuvant Chemo
NonseminomaLeast Intervention = Active Surveillance but risk chemo/RPLND
Avoid Any Chemo = Primary RPLND, may need Adj. Chemo
Avoid Surgery = Adjuvant BEP x1
Educating & Communicating with Patients
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