a review of the current testis cancer continuum: patterns, guidelines, needs and resources mike...

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


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


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

Increasing Incidence

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

Stage I >99%

Stage II 96%

Stage III 73%

Survival Rates


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?


AgeTumor Size

Rete Testis InvasionVascular Invasion

Epididymis InvasionhCG Level

Tunica Albuginea Invasion

No Validated Prognostic Factors for Recurrence Exist


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


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


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


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

TC-cancer.comCollective Experience of:10,000 Registered Users

15,000 Topics150,000 Posts

dialitdown.org

}244 Slices 3 Phases

Thank You

I love meeting new peopleand questions are my specialty so

please ask away!!

a review of the current testis cancer continuum: patterns, guidelines, needs and resources mike...

Documents

guys age

age30 http

leading cause of cancer

balance of benefits

health benefits

early diagnosis

risk factorswho

current evidence