Active Surveillance or Watchful Waiting – How do They Apply to Your Patients? 蒲永孝臺大醫院泌尿部主任臺大醫學院泌尿科教授臺灣楓城泌尿學會理事長

男性健康學園 NTU MEN‘S HEALTH ACADEMY – 2015-08-02

Active Surveillance or Watchful Waiting

– How do They Apply to Your Patients?

蒲永孝臺大醫院泌尿部主任

臺大醫學院泌尿科教授臺灣楓城泌尿學會理事長

台灣泌尿科醫學會常務理事臺大醫學院臨床醫學研究所博士


大部分攝護腺癌病人死於其他疾病

Lifetime risk of PC for western men is 15-20%, but the

lifetime risk of PC death is only 3%CA Cancer J Clin 2006; 56:106-30

45% of men with a PSA-detected PCa are candidates for

conservative management Eur Urol 2013; 63:101-7


Radical Prostatectomy vs Observation for

Localized Prostate Cancer (PIVOT study) 731 men eligible for surgery (median follow-up 10 yrs) No differences in overall or PC mortality RP: better CSS if PSA > 10 (p=0.04) and if intermediate or high-risk

tumors (p=0.07). But no differences at all for men > 65 years. More urinary incontinence and erectile dysfunction in men with RP Observation: watchful waiting, not active surveillance !!

NEJM 2012; 367: 203-213

Overall mortality PC mortality

P=0.22 P=0.09


N=695 Median FU: 13.4 yrs Better survival with RP than

with WW No survival benefit for men

> 65 yrs

NEJM 2011; 364: 1708NEJM 2014; 370: 932

Radical Prostatectomy vs WW

for Localized Prostate Cancer (SPCG-4)

65 65

<65<65

PC mortalityAll-cause mortality

Are Results of PIVOT contradictory to SPCG-4?

PIVOT SPCG-4*

Era PSA Pre-PSA

Mean age (year) 67 65

PSA > 10 34% 47%

Gleason 7 26% 32%

Stage T2 45% 69%

%High-risk 22% 24%

Enrollment Period 1994~2002 1989 ~1999

*Only 5% of subjects were diagnosed by screening.

More younger age in SPCG-4 More advanced tumors in SPCG-4 More prominent survival benefit from surgery in SPCG-4

><<<<

Surgery may confer survival benefit in younger men or men with more advanced or high-risk tumors.

Men > 65 years may not benefit from surgery.

National Taiwan Cancer Registry (2008~2010)

12,894 cases of incident prostate cancerMedian age at diagnosis: 74 yearsMedian age at death: 80 years

0

100

200

300

400

500

600

Age distribution

63%


Watchful Waiting vs Active Surveillance

WW (Obs) AS

Intention Palliative Curative

Potential subjects Short life expectancy Long life expectancy

Follow-up No agreed protocol Re-Biopsy, PSA kinetics, DRE, (MRI)

Timing to initiate treatment

Mets or local progression Progression criteria*

Treatment to be initiated

ADT, TUR-P, Urinary diversion, pall-

RT

Definitive treatments (Surgery, RT, etc.)

Introduced Before PSA era In past decade

*Progression in tumor grade, tumor size, cancer percentage or PSA kinetics

積極監控追蹤觀察


Clinical Case 1

75-year-old man (life expectancy: 10 15 years) Low-risk (PSA 8, Gleason 3+3=6, cT1cN0M0) Average health

Treatment plan?1. Active surveillance 2. Watchful waiting (observation)3. Definitive treatment (prostatectomy, radiotherapy, etc.) 4. Primary ADT

√√

√


Clinical Case 1

Low Risk


Clinical Case 1

Very Low Risk


Clinical Case 1

European Association of Urology 2014

EAU Guideline: Patients with low-risk PCa should be informed

about the results of two randomized trials comparing RP vs WW

in localized PCa.

In the SPCG-4 study, the survival benefit associated with RP was

observed in men with low-risk PCa, but only in men < 65 years.

In the PIVOT trial, a subgroup analysis of men with low-risk

tumors showed that RP did NOT reduce all-cause mortality, even

in men < 65 years. (not to mention men ≥ 65 years)


Active Surveillance: Advantages vs Disadvantages

Advantages:Reducing risk of unnecessary treatment of small, indolent cancersAvoiding side effects of definitive therapy that may be unnecessaryQuality of life/normal activities potentially less affected

Disadvantages:Chance of missed opportunity for cureSubsequent treatment may be complex with more side effectsNerve sparing may be more difficult, which may reduce chance of

potency preservation after surgeryIncreased anxietyNeeds frequent tests and re-biopsies, which may have

complicationsLong-term natural history of prostate cancer—unpredictable

2015 NCCN Prostate Cancer Guideline (Ver 1)


Observation (Watchful Waiting): Advantages vs Disadvantages

Advantage:Avoiding side effects of unnecessary definitive

therapy and early initiation and/or continuous ADT

Disadvantage:Risk of urinary retention or pathologic fracture

without prior symptoms or concerning PSA level

2015 NCCN Prostate Cancer Guideline (Ver 1)


Selection Criteria for Active Surveillance

EAU Prostate Cancer Guideline, 2014

Gleason 3+3 or 3+4 PSA 10-15 or PSAD 15% Clinical T T1/T2 Bx Pos cores 2 cores or 33% %cancer in core 20%~50%


Follow-up Protocol for AS

PSA every 6 mo DRE every 12 mo Repeat prostate biopsy

to be repeated within 6 mo of diagnosis if initial biopsy was <10 cores

if prostate exam changes or PSA increases, but neither is very reliable for detecting progression

as often as annually to assess progressionnot indicated when life expectancy < 10 y

PSADT: unreliable for assessing progression Multi-parametric MRI: not recommended for routine use,

unless to exclude possible anterior cancer

NCCN PC guideline 2015


Progression Criteria

Gleason Gr 4 or 5 cancer is found upon repeat prostate Bx

Prostate cancer is found in:

a greater number of biopsy cores

a greater extent in biopsy cores

Tumor grade criteria

Tumor size criteria

NCCN PC guideline 2015


Clinical Series with Active SurveillanceEAU Guideline 2014

J Clin Oncol 2010; 28:126


Long-Term Follow-Up of an Active Surveillance Cohort

Klotz, et. J Clin Oncol 2015; 33: 272

OS CSS

Mortality Mortality

N=993 (median FU: 6.4 years, 0.2 ~19.8 years) Only 1.5% died of PC The 10 &15-yr actuarial CSS: 98% and 94%, respectively. At 5, 10, and 15 years, 76%, 64%, and 55% of pts remained untreated. Non-PC to PC death: 9.2 : 1


Stage IV

Stage I 5-year survival

Stage I: 90%

Stage II: 92%

Stage III: 86%

Stage IV: 49%

Stage IIIUnknown

Stage II

Taiwan Prostate Cancer Database ConsortiumOverall Survival by Stage

10-year survival

Stage I: 83%

Stage II: 77%

Stage III: 71%

Stage IV: 28%


Stage IV

Stage I, II, III

5-year survival

Stage I: 100%

Stage II: 98%

Stage III: 98%

Stage IV: 64%

Taiwan Prostate Cancer Database Consortium

Cancer-Specific Survival by Stage

10-year survival

Stage I: 100%

Stage II: 94%

Stage III: 96%

Stage IV: 48%

98%

96%

Men with localized PC have a good survival.

RP

RT

CryoADT

Active Surveillance or WW

Nil

Taiwan Prostate Cancer Database Consortium

Treatments (Localized, T1-3N0M0)

US: 7%

US: 50%

US: 25%

US: 4%

US: 14%

Up to 30% of new patients at NTUH are now managed with AS/Obs.


Conclusions

Men with localized prostate cancer have a good

cancer-specific survival

AS/Obs is a viable option for patients with localized

PC

Men eligible for AS or WW:

Older age: > 65 for AS or <10 years of life expectancy for

WW

Low risk for AS

More co-morbidities for WW

Documents

Active Surveillance or Watchful Waiting – How do They Apply to Your Patients? 蒲永孝 臺大醫院泌尿部主任 臺大醫學院泌尿科教授 臺灣楓城泌尿學會理事長

Active Surveillance or Watchful Waiting – How do They Apply to Your Patients? 蒲永孝臺大醫院泌尿部主任臺大醫學院泌尿科教授臺灣楓城泌尿學會理事長