Christopher Saigal MD MPH Associate Professor UCLA Dept of Urology 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 Prehn’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 FOLLOW UP YEAR N* COMPLIANCE† Abdominal Imaging Chest Imaging Labs / Tumor Markers 100% ≥50% 0% 1 397 39.5% 14.9% 22.4% 56.7% 17.4% 25.9% 41.8% 10.3% 27.5% 2 227 15.9% 17.2% 39.6% 40.1% 20.3% 30.4% 11.9% 34.8% 3 110 3.6% 19.1% 45.5% 21.8% 30.9% 47.3% 25.5% 17.3% 39.1% 4 61 6.6% 31.1% 62.3% 42.6% NA 57.4% 27.9% 23.0% 49.2% 5 19 36.8% 63.2% 42.1% 57.9% 21.1% N* COMPLIANCE† Abdominal Imaging Chest Imaging Labs / Tumor Markers 100% ≥50% 0% Surveillance For Seminoma 1 397 39.5% 14.9% 22.4% 56.7% 17.4% 25.9% 41.8% 10.3% 27.5% 2 227 15.9% 17.2% 39.6% 40.1% 20.3% 30.4% 11.9% 34.8% 3 110 3.6% 19.1% 45.5% 21.8% 30.9% 47.3% 25.5% 17.3% 39.1% 4 61 6.6% 31.1% 62.3% 42.6% NA 57.4% 27.9% 23.0% 49.2% 5 19 36.8% 63.2% 42.1% 57.9% 21.1% Surveillance For NSGCT 23.7% 30.7% 12.3% 28.5% 21.4% 20.4% 5.3% 27.8% 3.1% 13.2% 18.2% 13.6% 29.1% 3.3% 8.2% 11.5% 16.4% 10.5% 31.6% Post - RPLND 96 68.8% 22.9% 8.3% 60.4% 33.3% 57.3% 16.7% 14.6% 37.7% 14.8% 29.5% 26.2% 28 60.7% 39.3% 17.9% 28.6% 25.0% 14.3% 32.1% 14 50.0% 42.9% 7 71.4% 85.7% Post - XRT 541 19.8% 30.1% 11.8% 28.8% 27.2% 15.3% 43.6% 16.5% 23.3% 309 19.7% 38.5% 41.7% 32.7% 36.2% 41.1% 31.7% 155 45.2% 54.8% 59.4% 40.6% 76 35.5% 64.5% 51.3% 48.7% 23 13.0% 87.0% 69.6% 60.9% 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 The survey also included 5 validated instruments: The Decision Regret scale – which measures our primary outcome as a surrogate for decision quality. The Short-Form 12 – which is a well established physical and mental HRQOL questionnaire. The Hospital Anxiety and Depression Scale, which measures negative psychosocial effects of somatic disorders. The Locus of Control Scale, which measures the relative importance of internal and external influences in patient preferences. And the Tolerance of Ambiguity Scale, which measures individuals’ perceptions and attitudes toward uncertain situations

PHYSICIAN CONSULTATIONS Urologist Oncologist RadOnc Seminoma Surveillance 1.2 0.4 1.1 XRT 1.3 0.5 0.9 NSGCT Surveillance 1.5 0.7 Chemo 1.0 1.2 RPLND 2.2 1.2 We asked patients about the types of physicians that they saw and how many they saw. Seminoma patients saw on average one Urologist and one RadOnc and were less likely to have seen an oncologist. NSGCT surveillance pts were less likely to have seen an oncologist than those who underwent chemotherapy or RPLND. RPLND patients saw an average of 2 Urologists and 1 oncologist.

DECISION INFLUENCE Urologist Oncologist RadOnc Seminoma Surveillance 4.3 4.7 4.8 XRT 4.5 4.5 4.6 NSGCT Surveillance 4.5 4.9 Chemo 4.5 4.6 RPLND 4.4 3.7 Family, friends, cost, time missed from work, internet mainly 2-3 Patients were then asked to rate on Likert scales of 1-5 the importance of other people’s opinions on influencing their decisions – 1 being not important and 5 being most important. XRT patients weighed their Urologist’s and RadOnc’s opinions equally, and seminomas that chose surveillance were more influenced by their RadOncs. RPLND patients weighed the opinion of their Urologists more highly than that of their oncologists, whereas surveillance NSGCT patients weighed the opinions of their oncologists more heavily. The opinions of family, friends and other cancer patients, were mildly important to unimportant, As were other factors as cost of treatment, time off for treatment, and information from the internet were also less important with scores of 4 or less, mostly in the 2-3 range.

COUNSELING ADEQUACY Urologist Oncologist RadOnc Seminoma Surveillance 4.3 4.3 4.8 XRT 4.2 4.4 4.4 NSGCT Surveillance 4.2 4.9 Chemo 4.0 4.4 RPLND 4.4 3.7 When asked if the men if they felt their physicians provided enough information to help them make a decision, patients were generally satisfied. Surveillance patients were slightly more satisfied with their RadOncs and Oncologists than their Urologists Whereas RPLND patients were slightly more satisfied with Urologists

PATIENT SATISFACTION Urologist Oncologist RadOnc Seminoma Surveillance 4.9 4.5 4.5 XRT 4.4 4.4 4.4 NSGCT Surveillance 4.6 4.8 Chemo 4.3 4.0 RPLND 4.2 4.0 When asked if they were satisfied with the care that they received , patients were generally satisfied. NSGCT patients who underwent surveillance experienced slightly greater satisfaction with the care they receive than those who underwent adjuvant therapy.

DECISION REGRET SCALE DRS Score Seminoma XRT 14.5 NSGCT Surveillance 15.5 Chemo 30.8 RPLND 20.4 Generally, men experienced little regret in their decisions – a score of 0 represents no regret, and 100 represents the highest level of regret. Surveillance patients demonstrated the least regret within both the Seminoma and NSGCT groups Suprisingly, patients who had recurrences and are now disease free have lower regret than those who underwent immediate treatment. In the case of seminoma patients, this finding was statistically significant.

OTHER INSTRUMENTS Short Form - 12: Tolerance of Ambiguity Scale: Physical component scores: Similar between treatment groups Higher than age matched population means Mental component scores Similar to age matched population means. Tolerance of Ambiguity Scale: Looking at the other instruments: The SF-12 showed similarities between all treatment groups, but testis cancer patients scored higher than the norms for age matched men in the general population. A previous study has also suggested that testis cancer patients have higher physical function scores than the general population, but may have lower mental health measures, which was not seen here. Patient’s abilities to tolerate ambiguous situations did not appear to affect decision choice.

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. While patient scores on the Hospital Anxiety and Depression Scale were similar between treatment groups, the means for all the scores were in the “borderline abnormal” range. The Locus of Control Scale showed that chance affects their decisions less than their own self-determination or the influence of “powerful others,” which in this case, represents the physician. Men that chose adjuvant therapy were more influenced by powerful others, and RPLND patients showed greater self- determination than those who underwent adjuvant therapy.

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 In conclusion: Influence of physicians appears to be the most important factor in testis cancer patients’ decision making – particularly in affecting patients’ choice of RPLND. Radiation oncologists and oncologists may be doing a better job of counseling patients than Urologists. In general, patients do not regret their decision choices, even among those that developed recurrences.

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 Consistent with previous studies, testis cancer survivorship may confer better perceived physical function QOL than the general population. Despite borderline anxiety and depression scores, patients did not show mental QOL impairment compared with the population, even among those who developed recurrences. Surveillance patients do not appear to experience more anxiety or depression than those who underwent active treatment.

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 All these trends suggest that clinical outcome may not be the ultimate determinate of Stage I testis cancer patient satisfaction And prospective studies are needed to evaluate the true effect of surveillance, active treatment, and recurrences on patient 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 Surveillance 279 30 mo $100,015 Surveillance For Seminoma $17,512 $11,703 Surveillance for NSGCT $20,950 RPLND 72 $119,903 $7,164 $13,005 XRT 388 28 mo $73,763 $5,280 $6,992

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.