Transcript A Review of the Current Testis Cancer Continuum

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
Denial
Fear
Upsetting
Others
“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
350
http://seer.cancer.gov/statfacts/html/testis.html
1 Guy
Every HOUR
Every DAY
DIAGNOSED
1 Guy
Every DAY
DIES
1 in 250 Diagnosed
Thanks to EARLY
Diagnosis and Treatment
1 in 5000 Dies
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
35
15
LEADING CAUSE
OCCURS AT ANY AGE
20
HIGHEST RISK
45
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
Quiz
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.
A. Current evidence is insufficient to assess the
I
balance of benefits and harms of attending a
University of Texas football game.
If the service is offered, patients should
understand the uncertainty about the balance of
benefits and harms.
B. There is moderate or high certainty that
D
attending a University of Texas football has no net
benefit or that the harms outweigh the benefits.
Discourage 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
lumps or
changes
it is important to
any
see a doctor
immediately.
www.BallChecker.com
Signs and Symptoms of Testicular Cancer
Enlargement of a Testicle
Loss of Size in one of the testicles
Feeling of Heaviness in the Scrotum
Dull Ache in the lower abdomen, back or groin
Pain or discomfort in the testicle or scrotum
Collection of fluid in the scrotum
Enlargement or tenderness in the breasts
Difficulty Breathing
STAGES
Image from Urology Care Foundation
Image from Urology Care Foundation
Image from Urology Care Foundation
Survival Rates
Stage I
>99%
Stage II
96%
Stage III
73%
http://seer.cancer.gov/statfacts/html/testis.html
Recent Reviews
TREATMENTS
Types of
Testicular
Cancer
Seminoma
NonSeminoma
Focus on Clinical Stage I Testicular Cancer
J Clin Oncology Vol 32, No 4_suppl, 2014: abstract 369
• Radiation
Therapy
• Chemotherapy
x 3-4 Cycles
Stage III
• Active
Surveillance
• Adjuvant
Chemotherapy
x 1 or 2 Doses
• Adjuvant
Radiation
Therapy
Stage II
Stage I
SEMINOMA
• Chemotherapy
x 3-4 Cycles
• RPLND
• Chemotherapy
x 3-4 Cycles
Stage III
• Active
Surveillance
• Adjuvant
Chemotherapy
x 1 or 2 Cycles
• RPLND
Stage II
Stage I
NONSEMINOMA
• Chemotherapy
x 3-4 Cycles
International Germ Cell Consensus Classification:
a prognostic factor-based staging system
for metastatic germ cell cancers.
Percent of
GCTs
Good Prognosis
60%
5-year
Survival
Rate
91%
Intermediate
Prognosis
Poor Prognosis
26%
79%
14%
48%
J Clin Oncol. 1997 Feb;15(2):594-603.
Seminoma Risk Stratification
Primary
Tumor
Metastasis
Status
Tumor Marker
Status
Low Risk
Any
No Nonpulmonary
Visceral Metastasis
Normal AFP
Any b-hCG
Any LDH
Intermediate
Risk
Any
Nonpulmonary
Visceral Metastasis
Normal APP
Any b-hCG
Any LDH
No Seminomas are considered High Risk
Nonseminoma Risk Stratification
Primary
Tumor
Metastasis
Status
Tumor Marker
Status
Low Risk
Testis or
No Nonpulmonary
ALL
Retroperitoneal
Visceral
AFP <1,000
Metastasis
B-hCG <5,000
LDH <1.5x ULN
Intermediate
Risk
Testis or
No Nonpulmonary
ANY
Retroperitoneal
Visceral
AFP 1,000 – 10,000
Metastasis
B-hCG 5,000 – 50,000
LDH 1.5x – 10x ULN
High
Risk
Testis or
Retroperitoneal
or Mediastinal
Mediastinal
Primary or
Nonpulmonary
Visceral
Metastasis
ANY
AFP > 10,000
B-hCG > 50,000
LDH > 10x ULN
Treatment by Risk Stratification
Chemo
Regimen
Chemo
Regimen
Low Risk
BEP x 3
or
EP x 4
EP
Etoposide
Cisplatin
Intermediate
Risk
BEP x 4
or
VIP x 4
BEP
Bleomycin
Etoposide
Cisplatin
High
Risk
BEP x 4
or
VIP x 4
VIP
Etoposide
Ifosfamide
Cisplatin
50.3%
CS I LVINonseminoma had
Adjuvant Chemo
J Clin Oncology Vol 32, No 4_suppl, 2014: abstract 369
Barriers to
Active 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.
Cure Rates
Approach
100%
J Clin Oncol. 2013 Oct 1;31(28):3490-3.
Cancer. 2014 Oct 24. doi: 10.1002/cncr.29094.
NS
NS
Cancer. 2014 Oct 24. doi: 10.1002/cncr.29094.
Clinical Stage I Seminoma
Option
Active Surveillance
Outcomes
20% Relapse.
Advantage
No treatments
99% Long-term
CSS
Who is going to relapse?
Adjuvant Radiation
Therapy
4% Relapse.
99% Long-term
CSS
Adjuvant
Carboplatin
x1 or x2 Doses
4% Relapse.
99% Long-term
CSS
Disadvantage
Relapse means
higher doses of
Radiation Therapy
or Full-Dose Chemo
w/ Residual Mass
Management.
Reduced relapses &
need for Chemo &
Freq. of Abd.
Imaging
Short-term side
effects & Long-term
risk of Secondary
Malignancy
Reduced relapses &
need for Chemo &
Radiation.
Short-term side
effects & Long-term
risks unknown.
Clinical Stage I Seminoma
Age
Tumor Size
Rete Testis Invasion
Vascular Invasion
Epididymis Invasion
hCG Level
Tunica Albuginea Invasion
No Validated Prognostic Factors for Recurrence Exist
1954 CSI Seminoma Patients on Surveillance
Clinical
Stage
I
Seminoma
(median follow-up time 15.1 years)
DSS at 5, 10 and 15 years
99.6%, 99.4% and 99.3%
18.9% (n=369) Relapsed
(median time of 13.7 months)
95.7% of Relapses were in 5 years
4.3% of Relapses after 5 years
99.5% Good Prognosis Risk
0.5% Intermediate Prognosis Risk
Eur Urol. 2014 Dec;66(6):1172-8.
Clinical Stage I Seminoma
Eur Urol. 2014 Dec;66(6):1172-8.
Clinical Stage I Nonseminoma
Option
Active Surveillance
Outcomes
30% Relapse.
Advantage
Disadvantage
No treatments
Relapse means
Full-Dose Chemo w/
Residual Mass
Management.
Reduced relapses &
need for Chemo &
Freq. of Abd.
Imaging
Surgical Risks.
Reduced relapses &
need for Chemo
Long-term Risks
Unknown.
15% Low-Risk
Group
50% High-Risk
Group
Retroperitoneal
Lymph Node
Dissection (RPLND)
20-30% Relapse.
Adjuvant BEP
x1 or x2 Cycles
1-5% Relapse.
Lymphovascular Invasion
99.7% 5- and 10-year
Disease Specific Survival
J
J Clin Oncol. 2015
2013 Jan
Oct 1;31(28):3490-3.
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 Prognosis
1.2% of Relapses were Intermediate Prognosis
No Patients died from Seminoma
1 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 Overall
44% LVI+ Relapsed
14% 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 Nonseminoma
2 Patient Died from Treatment-Related Complications
99.4% 5-yr DSS
J Clin Oncol. 2015 Jan 1;33(1):51-7.
5-7 CTs
NCCN = 6-9 CTs
6-7 CTs
J Clin Oncol. 2015 Jan 1;33(1):51-7.
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)
Risk Factors
VI+, Rete Testis Invasion, Embryonal
26% PC-RPLND (8% total population)
94.4%, 4.7% & 0.8% of Relapses were Good, Intermediate
and Poor Prognosis (2% unclassified)
6 Patients died from Nonseminoma
4 Patient Died from Treatment-Related Complications
99.1% 15-yr DSS
J Clin Oncol. 2014 Dec 1;32(34):3817-23.
J Clin Oncol. 2014 Dec 1;32(34):3817-23.
Adjuvant Therapy
Stage I Seminoma
Adjuvant radiation therapy has fallen out of favor.
Carboplatin x1 or x2 Doses?
Stage I Nonseminoma
Adjuvant BEP x1 or x2 Cycles?
Relapses after Adjuvant BEP Chemo-Resistant?
European Urology 67 (2015) 544–545
517 patients, BEPx1, media follow up 7.9 years
2.4% Overall Relapse Rate
3.2% Relapse LVI+
1.6% Relapse LVI5- & 10-year CSS = 100% & 99.6%
100% & 99.3% for LVI+
100% & 100% for LVIAnn 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.
4% Retroperitoneal Relapse Rate
Community-based Study
1.2% Tertiary Referral Centers
7.937
(95% CI, 1.808 to 34.48)
J Clin Oncol. 2008 Jun 20;26(18):2966-72
J Clin Oncol 32:5s, 2014 (suppl; abstr 4519)
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?
J Urol. 2015 Feb;193(2):507-12.
J Urol. 2015 Feb;193(2):513-8.
National Second-Opinion Project
on Testicular Cancer
39.5% Discordance
in 926 patients
Second-opinion Discordance
28.1% Less Extensive
15.6% More Extensive
56.3% No Difference in Scope
69% (462/668) applied 1st or 2nd Opinion
85.3% Second vs. 14.7% First
31% Used Neither
Access to Care
European Urology 67 (2015) 544–545
p<0.0001
J Urol. 2014;191(4):e90.
p=0.025
J Urol. 2014;191(4):e90.
For Every 100 Young Men Insured
6 Reduced
Treatment
Burdens
1
Life
Saved
J Urol. 2014;191(4):e90.
The Key to Testicular Cancer Care
is 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 Approach
Educating the patients to risks vs. benefits
Individualization based on Patient & Risk Aversion
Assessing Risk on Noncompliance & Access to Care
Assessing Coping Ability & Level of Distress
Considering Life Disruptions by Relapse
Patient-Centered Approach
Seminoma
Least Intervention = Active Surveillance but risk full chemo
Avoid Any Chemo = Adjuvant Radiation (esp. in older pts.)
Avoid Radiation = Active Surveillance or Adjuvant Chemo
Nonseminoma
Least 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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