colorectal cancer post-treatment surveillance robert fry, md emilie & roland dehellebranth...

Colorectal Cancer Post-Treatment Surveillance

Robert Fry, MD

Emilie & Roland deHellebranth Professor

Chief, Division of Colon & Rectal Surgery

Chairman, Department of Surgery

Pennsylvania Hospital

Department of Surgery, University of Pennsylvania Health System

Lifetime Probability of Developing Cancer, Women, USA, 2002-2004

Site Risk

All sites† 1 in 3

Breast 1 in 8

Lung & bronchus 1 in 16

Colon & rectum 1 in 19

Uterine corpus 1 in 41

Non-Hodgkin lymphoma 1 in 53

Melanoma 1 in 61

Ovary 1 in 71

Pancreas 1 in 76

Urinary bladder‡ 1 in 85

Uterine cervix 1 in 142 Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.2.1 Statistical Research and Applications Branch, NCI, 2007. http://srab.cancer.gov/devcan

Lifetime Probability of Developing Cancer, Men, USA, 2002-2004

Site Risk

All sites† 1 in 2

Prostate 1 in 6

Lung and bronchus 1 in 13

Colon and rectum 1 in 18

Urinary bladder‡ 1 in 27

Melanoma 1 in 41

Non-Hodgkin lymphoma 1 in 46

Kidney 1 in 59

Leukemia 1 in 67

Oral Cavity 1 in 71

Stomach 1 in 88Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.2.1 Statistical Research and Applications Branch, NCI, 2007. http://srab.cancer.gov/devcan

Trends in Five-year Relative Survival (%) Rates, US, 1975-2003

Site 1975-1977 1984-1986 1996-2003• All sites 50 54 66

• Breast (female) 75 79 89

• Colon 51 59 65

• Leukemia 35 42 50

• Lung and bronchus 13 13 16

• Melanoma 82 87 92

• Non-Hodgkin lymphoma 48 53 64

• Ovary 37 40 45

• Pancreas 2 3 5

• Prostate 69 76 99

• Rectum 49 57 66

• Urinary bladder 74 78 81

Value of a Human Life

• 1987: 21 states raised speed limits from 55 mph to 65 mph

• Speeds increased 3.5% (2 mph)• Fatality rates increased 35%• 125,000 hours saved/life lost

Orley Ashenfelter, Princeton University Michael Greenstone, University of Chicago

April, 2002


• Consider average hourly wage (1997$)

• Dollars saved/lives lost = $1.54 M/life

• $1,540,000.00*

Orley Ashenfelter, Princeton University Michael Greenstone, University of Chicago

April, 2002

*Sampling error around 1/3 of this value

Value of a Human Life: EPA• Earning ability or wealth not relevant• Two survey studies on avoiding risks

– $8.8 M (Kip Viscusi, Vanderbilt University)– $2-3.3 M (Laura Taylor, N Carolina State U)

• What people pay to avoid risk• How much extra employers pay to take on risk

• Old value: $7.8 million• New value: $6.9 million

Seth Borenstein, Associated Press, Jul 10, 2008

Value of a Human Life: EPA

• Hypothetical Regulation–$18 Billion to enforce–prevents 2,500 deaths

• Worth it at $7.8 M (old figure)–$18 B/2500 = $7.2 M

• Not cost effective at $6.9 M


Value of a Human Life: EPA

• An ever changing value–Decreasing value of the dollar

implies decreasing value of life–2002: EPA decided value of elderly

people to be 38% less than people younger than 70• Decision reversed after it became

public


Cost Utility Analysis (CUA)A type of cost-effectiveness study that combines mortality and morbidity data into a single multidimensional measure:

QALY(the quality-adjusted life year)

Canadians: $20,000 (Can 1992)/QALY definitely cost effective

$20K to $100K (Can 1992)/QALY only possibly cost-effective

Americans: $50,000 (U.S. 1992)/QALY*

*Cost of end-stage renal dialysis, from 1973

Earle CC, Chapman RH, Baker CS, et al: Systematic overview of cost-utility assessments in oncology. J Clin Oncol 18:3302-3317, 2000.


• In theory: Priceless

• In traditional reality: $50,000/year

• In U.S. today: $129,000/year– Stafanos Zenios et al, Stanford Graduate

School of Business– Computer analysis of 500,000 dialysis

patients, comparing costs to outcomes

Kingsbury, K. Time/CNN, May 20, 2008

ASCO Outcomes That Justify Diagnostic Tests or Treatments

Outcomes that

justify use

Outcomes that do

not justify use

Improved overall survival Earlier knowledge about recurrence

Improved disease-free survival

Unproven hope that earlier detection leads to better care or palliation

Better quality of life Cost alone

Less toxicity

Improved cost-effectiveness

Cost of Patient Follow-up for Five Years after Potentially Curative Colorectal Cancer Treatment

Low: $910.00

High: $26,717.00

Indications that High-cost Strategy Saves lives: Nill.

Virgo KS, Vernava AM, Longo WE, McKirgan LW, Johnson FE, JAMA 273:1837-1841, 1995.

Department of Surgery, University of Pennsylvania Health System

Secco GB, Fardelli R, Gianquinto D, Bonfante P, Baldi E, Ravera G, et al: Efficacy and cost of risk adapted follow-up inpatients after colorectal cancer surgery: a prospective, randomized and controlled trial. European Journal of Surgical Oncology 2002;28:418-423.

“The annual and total costs (euros) of risk-adapted follow-up over a period of 5 years were calculated as the sums of the cost of each diagnostic test considering the costs of materials, of depreciation of equipment and the cost of medical personnel, technicians and nursing staff per minute.”


“Risk-adapted follow-up reduced the costs of disease-free patients in the relaxed follow-up group as compared with the intensive follow-up patients.”


“Risk-adapted follow-up reduced the costs of disease-free patients in the relaxed follow-up group as compared with the intensive follow-up patients.”

DOH!Homer Simpson

Jeffery M, Heckey BE, Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database of Systematic Reviews 2007, Issue 1. Oxford, United Kingdom, Cochrane Library, CD002200.

• Review evidence concerning benefits of intensive follow up with respect to survival

• Secondary endpoints– Time to dx of recurrence– Quality of life– Harms– Costs

• 8 Randomized Controlled Trials

Cochrane Review Conclusions

• Overall survival benefit!• Cannot determine the appropriate

– Clinic visits

– Blood tests

– Endoscopic procedures

– Radiological investigations

Cochrane Review Conclusions

• Overall survival benefit!• Cannot estimate

–Potential harms

–Costs

Methods of Follow-up

• History taking

• Abdominal & Rectal Exam

• Sigmoidoscopy (for rectal CA)

Clinical Examination

Signs/Symptoms would have (could have) indicated recurrence in 21-48% of patients.


• LFTs: worthless

• Hgb/Hct: pretty much worthless

• CEA: most cost effective test

Blood Tests


• 1st indication of recurrence in 60%• Sensitivity about 80%• 30% do not express antigen• False positive 5 – 15%• Better for distant recurrence• Median lead time: 6 months

CEA

Cost per Recurrence

• CEA $5,696

• Physical Exam$418,615

Papagrigoriadia, S. International Journal of Surgery (2007) 5, 120-128.


• Colonoscopy (more for metachronous tumors)

• Sigmoidoscopy/Proctoscopy

Direct Imaging


• US: regular intervals 1st 2-3 years• CT scan (MRI)• Chest X-ray (not routine)• PET (not routine)

Radiology

Follow-up for Colorectal Cancer:Ideal Combination of Tests

• High diagnostic accuracy

• Minimally invasive

• Not affect quality of life

• Cost-efficient

Papagrigoriadia S. International Journal of Surgery 2007

325 Prospectively Randomized Follow-up for Colorectal Cancer

• Q 3 months for 2 yrs:– Symptoms and Signs– CBC, LFTs, CEA– Fecal occult blood

• Then Q 6 months

• Q 3 months for 2 yrs:– Symptoms and Signs– CBC, LFTs, CEA– Fecal occult blood

and YEARLY– CXR– CT of liver– Colonoscopy

Standard Intensive

Schoemaker D, et al. Gastroenterology, 1998

325 Prospectively Randomized Follow-up for Colorectal Cancer

• Colonoscopy, CT, CXR have no survival benefit

• Do colonoscopy 5 years after operation• CXR & CT used to investigate symptoms

or LFT changes

Conclusions

Schoemaker D, et al. Gastroenterology, 1998

Mayo Clinic Calculator

Prognostic Factors 5-yr relapse-free survival

T3N0 (>10 nodes) 79%

T3N0 low grade 73%

T3N0 (< 10 nodes) 72%

T3N0 high grade 65%

T4N0 low grade 60%

T4N0 high grade 51%

T3N1 49%

T3N2 15%

Individual patient data from 12,915 patients on 15 randomized trials:

85% of colon cancer recurrences are diagnosed with 3 years of resection.

Sargent DJ, Wieand S, Benedetti J, et al: J Clin Oncol 22: 2004 (abstr 3502)

Practice GuidelineASCO 2005 Update

• Office visits q 3 – 6 months for 3 years, then decreased frequency

• CEA q 3 months for Stage II or III initiate after adjuvant therapy completed

• CT of chest and abd yearly for 3 years

• CT of pelvis for rectal cancer patients

• Colonoscopy: perioperative and at 3 years

• Procto: for rectal ca without RT q 6 monthsJ Clin Oncol 23:8512-8519, 2005.


• CBC and LFT

• Fecal occult blood test

• Yearly chest xrays

• Molecular or cellular markers

NOT RECOMMENDED:

J Clin Oncol 23:8512-8519, 2005.


3 meta-analyses demonstrate survival for CT or “liver imaging”

Why CT Scans?

J Clin Oncol 23:8512-8519, 2005.

25% decreased mortality with liver imaging compared to nonimaging strategies


• 530 patients, Stage II and III • CEA: 45 relapses• CT: 49 relapses• Both: 14• Relapses detected by either had

improved survival compared to those detected by symptoms

Why CT Scans?

Chau I, Allen MJ, et al: J Clin Oncol 22, 2004.


1. Detects largest number of resectable recurrences.

2. CEA elevation less likely with pulmonary metastases

3. Lung as common as liver mets in rectal cancer patients

4. Replaces Chest X-rays

Why Chest CT Scans?

J Clin Oncol 23:8512-8519, 2005.

Unanswered Questions

• Two tiered follow-up?– More intense for more aggressive

tumors?

• PET scans?

• Molecular markers?

colorectal cancer post-treatment surveillance robert fry, md emilie & roland dehellebranth...

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