Testis Cancer

Christopher Saigal MD MPH Associate Professor UCLA Dept of Urology

• Differential • Burden of illness • Screening • Diagnosis • Treatment • Patient centered outcomes

Differential

Differential of a scrotal mass:

History: Time course, associated pain, constitutional symptoms, exacerbating factors, etc Past medical history: undescended testis, maternal DES exposure, h/o contralateral tumor

Evaluation of Scrotal Mass

• Physical exam: Vitals Pain, redness, heat, reducibility, orientation of testis Phren’s sign Transillumination Cremasteric reflex • UA, urine culture • Ultrasound

Differential: Hydrocele

Differential: Epididymo-orchitis

• Epididymitis is most common • Usually an ascending infection thru vas deferens • Age predicts causative organism >35 yrs: coliform bacteria 12-35 yrs: chlamydia, gonorrhea <12: coliform, ?viruses

Differential: Spermatocele/ Epididymal cyst

•

Differential: Varicocele

Differential: Testicular Torsion

Differential: Hernia

Reducible or incarcerated Usually does not transilluminate Swells with valsalva

Differential: benign testicular lesions

Very rare. Ultrasound may be suggestive • epidermoid cysts • fibromas • fibroadenomas • adenomatoid tumors • lipomas

Differential: testis tumor

• Physical exam ?gynecomastia (found in 5%) adenopathy abdominal mass

Burden of Illness • Incidence rose from 3.5 to 6.5/100,000 over 30 years • About 6,000 cases/yr • Survival is > 90% • For all males, lifetime probability of dying of testes cancer is 0.02% SEER

Testicular Cancer: Is Screening Accurate

Can screen via: Testicular self exam: Low specificity: about 8% of men

with

a “lump” found to have a tumor Buetow J, Med Screen. 1996 Testicular ultrasound: Highly sensitive and specific

Does Screening Improve Outcomes?

• US Preventative Services Task Force 4/2004 Review • No evidence of decreased mortality • 5 yr survival is >90%

without

screening • Risk of false positives with TSE • Cannot recommend screening

Diagnosis

Diagnosis

Diagnosis

Ultrasound is highly specific (hypoechoic lesion), but diagnosis is made at radical orchiectomy Microlithiasis- not a risk factor Biopsy contraindicated

Histologic types

Germ cell tumors: Seminoma versus Non seminomatous germ cell tumors (NSGCT) Non-germ cell tumors (rare, <5%) Leydig cell tumors (precocious puberty) Sertoli cell tumors Mixed sex chord-stromal tumors

NSGCT

• Choriocarcinoma (elevated b-Hcg) • Embryonal cell • Teratoma (mature and immature) • Yolk sac (elevated AFP)

Seminoma

• Rarely make hcg • Generally favorable prognosis when seen in older men

Tumor markers

• AFP levels are elevated 50%-70% NSGCT • hCG levels are elevated in 40%-60%. • AFP has a half-life of 5-7 days • hCG has a half-life of 36 hours. • Important to follow response after orchiectomy • LDH is non-specific measure of tumor burden

Treatment

• Staging CT scan miss microscopic disease in 1 in 3 to 1 in 5 men • % embryonal cell, LV invasion, T stage can be predictive or RP disease • Dilemma: overtreat or undertreat?

Treatment

Seminoma

Stage IA and B:  radiation therapy vs surveillance (? Chemo)

NSGCT

Stage IA  retroperitoneal lymph node dissection vs surveillance Stage IB  retroperitoneal lymph node dissection vs surveillance vs chemotherapy Higher stages  chemo, f/b surgery as needed

Endocrine issues

• Higher proportion of oligospermic men • Sperm banking recommended before adjuvant therapy • Treatment can damage testis, decrease T levels • Leydig cell tumors, some that produce B hcg can cause gynecomastia

Retroperitoneal Lymph Node Dissection

chemotherapy

• Usually 2 cycles of BEP • Well tolerated • ? Late effects • Effects on fertility

Surveillance

NCCN guidelines • CT q 2-3 months for first year or two • Then q4, q6 • Labs, CXR q month for year one, then q 2 months, etc • Issues are compliance, anxiety

Quality of Surveillance for Stage I Testis Cancer in the Community Stage I Testis Cancer Compliance With Surveillance Follow Up Guidelines for Seminoma Surveillance For Seminoma Surveillance For NSGCT 2 Post 4 Post - XRT 5 N* 5 1 397 2 3 4 227 5 1 1 2 3 4 110 3 4 61 2 5 1 2 3 19 4 5 N* 397 110 61 397 227 0% 61 19 61 28 7 541 309 155 76 23 Abdominal Imaging 100% 39.5% 15.9% 3.6% 6.6% 0% 23.7% 5.3% 3.6% 6.6% 68.8% 62.3% 50.0% 28.6% 19.7% 45.2% 13.0% ≥50% 14.9% 17.2% 19.1% 31.1% 36.8% 30.7% 27.8% 19.1% 31.1% 22.9% NA NA NA 38.5% NA NA 0% 22.4% 39.6% 45.5% 62.3% 63.2% 22.4% 39.6% 45.5% 62.3% 8.3% 37.7% 50.0% 71.4% 41.7% 54.8% 87.0% COMPLIANCE † COMPLIANCE † 100% 56.7% 21.8% 42.6% 42.1% 12.3% ≥50% 17.4% 20.3% 30.9% NA NA 28.5% 0% 0% 25.9% 39.6% 47.3% 57.4% 57.9% 25.9% 3.1% 3.6% 17.4% 20.3% 18.2% 39.6% 47.3% 3.3% 8.2% 57.4% 60.4% 27.9% 14.3% 0% 28.8% NA 32.7% 59.4% 51.3% 30.4% NA 31.6% 33.3% 37.7% 28.6% 28.6% 14.3% 27.2% 36.2% NA NA NA 0% 14.8% 14.3% 85.7% 31.1% 40.6% 69.6% Labs / Tumor Markers 100% 41.8% 25.5% 27.9% 21.1% 21.4% 13.2% 13.6% 11.5% 57.3% 23.0% 14.3% 28.6% 41.1% 59.4% 60.9% ≥50% 10.3% 11.9% 17.3% 23.0% 21.1% 20.4% 17.2% 29.1% 16.4% 16.7% 29.5% 21.4% 42.9% 27.2% NA NA 0% 27.5% 34.8% 39.1% 49.2% 57.9% 27.5% 34.8% 39.1% 49.2% 14.6% 26.2% 42.9% 28.6% 31.7% 40.6% 39.1%

•

401, 96, and 541 patients received surveillance, RPLND and XRT, respectively.

•

Mean follow up was 23, 24 mo, and 23 months, respectively. 100% of surveillance patients had at least one follow up test in the first year, but 8-16% of patients had no follow tests of any kind in years 2-5.

•

Compliance with recommended follow up was generally poor.

•

Compliance with follow up was higher in RPLND patients.

Quality of Surveillance for Stage I Testis Cancer in the Community

•

The use of surveillance for testis cancer is widely accepted in the community.

•

Compliance rates with recommended follow up care are poor .

•

Compliance among RPLND patients appear to be superior, possibly due to greater selection for motivated patients.

•

Surveillance protocols developed at referral centers are not being followed in the community; further work is needed to understand the impact of this apparent quality of care problem on oncologic outcomes in men treated in the community with surveillance protocols.

Testicular Cancer outcomes

5 year survival for stage I is >95% Focus is on reducing treatment side effects (e.g. retrograde ejaculation) Concern over late effects of treatment

Patient Perspectives

California Cancer Registry study

• Decision Regret Scale • Short Form - 12 • Hospital Anxiety and Depression Scale • Locus of Control Scale • Tolerance of Ambiguity Scale • Questions about influencers, satisfaction

PHYSICIAN CONSULTATIONS

Seminoma Surveillance XRT NSGCT Surveillance Chemo RPLND Urologist 1.2

1.3

Oncologist 0.4

0.5

1.5

1.0 2.2

0.7

1.2

1.2

RadOnc 1.1

0.9

DECISION INFLUENCE

Seminoma Surveillance XRT NSGCT Surveillance Chemo RPLND Urologist 4.3

4.5

Oncologist 4.7

4.5

4.5

4.9

4.5 4.6

4.4

3.7

RadOnc 4.8

4.6

Family, friends, cost, time missed from work, internet mainly 2-3

COUNSELING ADEQUACY

Seminoma Surveillance XRT NSGCT Surveillance Chemo RPLND Urologist 4.3

4.2

Oncologist 4.3

4.4

4.2

4.9

4.0 4.4

4.4

3.7

RadOnc 4.8

4.4

PATIENT SATISFACTION

Seminoma Surveillance XRT NSGCT Surveillance Chemo RPLND Urologist 4.9

4.4

Oncologist 4.5

4.4 4.6

4.8

4.3 4.0

4.2

4.0

RadOnc 4.5

4.4

DECISION REGRET SCALE

Seminoma NSGCT XRT Surveillance Chemo RPLND DRS Score 14.5

15.5

30.8

20.4

OTHER INSTRUMENTS

• Short Form - 12: – Physical component scores: • Similar between treatment groups • Higher than age matched population means – Mental component scores • Similar between treatment groups • Similar to age matched population means.

• Tolerance of Ambiguity Scale: • Similar between treatment groups

OTHER INSTRUMENTS

• Hospital Anxiety and Depression Score: • Similar between treatment groups • All groups scored in the borderline abnormal range • Locus of Control Scale: • Influence of chance < internal < powerful others.

• Adjuvant therapy patients influenced more by powerful others.

• RPLND patients have stronger internal LCS than other treatment groups.

CONCLUSIONS

• Influence of the MD is important • RadOncs and Oncologists may doing better job of pt counseling • Pts generally tolerate surveillance and treatments well and do not regret their choice

CONCLUSIONS

 Despite borderline anxiety and depression scores, pts do not show mental QOL impairment compared with population – including recurrences  Surveillance pts do not experience more anxiety or depression

CONCLUSIONS

 Clinical outcome may not be the ultimate determinate of patient satisfaction  Prospective studies need to be done to evaluate true effect of surveillance vs treatments and the effects of clinical recurrence on pt satisfaction and QOL

Surveillance and Treatment Expenditures of Stage I Testis Cancer Stage I Testis Cancer Follow Up Expenditures N Mean Follow-Up Total Expenditures (5-Year) NCCN Based Projection of 5-Year Follow-Up Test Expenditures 5-Year Follow-Up Test Expenditures Surveillance For Seminoma

Surveillance and Treatment Expenditures of Stage I Testis Cancer

•

Long-term expenditures for stage I testis cancer are lowest after XRT.

•

Expenditures for surveillance were less than that for RPLND, but greater than that for XRT, even though no active treatment occurs.

•

Follow-up tests do not account for the bulk of expenditures - surveillance patients are incurring more expenses related to physician and hospital services, including treatment for recurrences.

•

Actual expenditures may vary from projected models due to high rates of non compliance with follow up protocols.

•

Prospective studies on the clinical and economic impact s of surveillance noncompliance within the community need to be done.