Survivorship care and research Craig Earle, MD MSc FRCPC Director, Health Services Research Program for Cancer Care Ontario & the Ontario Institute for Cancer Research

Objectives (key messages) Communicating with patients about the plan for follow up can go a long way towards decreasing anxiety Be judicious about the intensity of follow-up www.nccn.org Be open to non-oncologist based models of survivor care

Incidence + survival = demand

Next 10 years Ontario to see 40% increase in people living with cancer J. Natl. Cancer Inst. 2008 100:236; doi:10.1093/jnci/djn018 Next 10 years Ontario to see 40% increase in people living with cancer By 2017, the estimated number near half a million (406,000)

Survivor Definitions Medical Model: disease-free 5 yrs after completion of therapy Advocate: a person with cancer is a survivor from the time of diagnosis through the remainder of life National Coalition for Cancer Survivorship. Charter. Silver Spring, MD: National Coalition for Cancer Survivorship, 1986. Include family members and caregivers as well? Gleevec and CLL pts

Cancer Care Trajectory

Current survivorship care models in Canada Follow-up care varies markedly, especially Ontario Follow-up care in cancer centre Transfer of care to FP Variable practices

Problems with the status quo Dissatisfaction Variable quality of care Workforce issues

1. Dissatisfaction

Ontario Cancer Plan: explicit goal to improve the patient experience along every step of the cancer journey A particular area of patient dissatisfaction on survey 11

Communication and information needs

Many survivors have little or no long-term problems, and some have positive effects

“It’s not over when it’s over” Patti Ganz Journal of Oncology Practice 2006;2(2):79

Myths about Ending Treatment I should be celebrating I should feel well now I should be back to my pre-cancer self I shouldn’t need support anymore Stanton, Ganz,, Rowland, et al Cancer. 2005.

The truth about ending treatment Counter to the expectation that treatment completion and full recovery of health and well being occur simultaneously, the literature suggests that treatment completion can be disruptive psychologically. Promoting adjustment after treatment for cancer Annette L. Stanton, Patricia A. Ganz, Julia H. Rowland, Beth E. Meyerowitz, Janice L. Krupnick, Sharon R. Published Online: 24 Oct 2005

“No one warned me that once treatment was over everything would change “No one warned me that once treatment was over everything would change. I was like a rock star while I was having treatment--then poof, I’ve been dropped off of the map and no one seems to care much anymore. “ prostate survivor, reflecting on the first few months off treatment

“When I was in treatment, I had all the steps laid out in front of me “When I was in treatment, I had all the steps laid out in front of me. I knew what I had to do to fight this disease. Now, I find myself wanting to go to clinic, to be getting chemo, to DO SOMETHING. I am just sitting here, alone now, waiting for it to come back.” Breast ca survivor, 4 weeks out

From Cancer Patient to Cancer Survivor: Lost in Transition - Institute of Medicine, November 2005 (www.iom.edu)

IOM Recommendation #1 Recognize cancer survivorship as a distinct phase of cancer care

Survivorship is a distinct clinical entity with its own cross-cutting issues Surveillance Recurrence Local Distant New cancers Genetic/environmental predisposition Late & persistent effects of treatment Organ dysfunction, mobility, fatigue, lymphedema, hormonal/sexuality/fertility, second cancers Non-cancer care Screening/prevention Other medical conditions Lifestyle/behavioral interventions Employment/insurance (health, life, disability) Psychosocial Fear, relationships, cosmesis, cognitive

IOM Recommendation #2 Patients completing primary treatment should be provided with a comprehensive care summary and follow-up plan … (the) ‘survivorship care plan’

Provider-provider communication

Why are there MD communication problems in cancer in particular? Multidisciplinary care An average of > 3 cancer doctors /patient Complex Treatment takes place in a variety of settings (inpatient, outpatient, specialized facilities) across time and space Multiple medical records Often takes place in isolation from PCPs

2. Variable quality of care

Follow up practices for breast cancer, Hodgkin’s disease, colorectal cancer, and endometrial cancer in Ontario Large variation in practice Both over-use and under-use of visits and tests compared to published guidelines Grunfeld et al J Oncol Pract. 2010 Jul;6(4):174-81. Hodgson et al Cancer. 2010 Jul 15;116(14):3417-25) Kwon et al. Obs Gyn 2009;113(4): 790-795

Surveillance components History and Physical Blood work, including tumor markers Imaging Examination of the primary site (e.g., endoscopy, mammography)

Surveillance for recurrence Problem: Lack of evidence ASCO – Strict evidence-based: only breast and colorectal guidelines (incl. tumor markers) NCCN – evidence-based consensus (www.nccn.org) ESMO – evidence-based consensus (Ann Oncol. 2005;16 Suppl 2) ‘Cancer Patient Follow Up’ (Johnson & Virgo) – Expert opinion In some cases, lack of rationale Does surveillance detect recurrence earlier than it would otherwise become apparent? If so, does early intervention improve the outcome of recurrent disease? If so, does it do so in a cost-effective manner? Everyone wants evidence-based recommendations for surveillance, but the problem is a lack of evidence Consequently, ASCO only has guidelines for breast and colorectal cancer follow up The National Comprehensive Cancer Network, which takes a less strict evidence-based approach to their consensus guidelines incorporate recommendations for follow up into their algorithms, and the European Society of Medical Oncology published a supplement last year with recommendations for follow up of many different cancers There’s a whole textbook devoted to this topic by Frank Johnson and Kathy Virgo in which they survey experts from around the world in order to compare their follow up practices In addition to a lack of evidence, in many cases there’s even a lack of rationale. Aside from a few examples, like oligometastatic recurrence of colorectal cancer, most solid tumors cannot be cured once they metastasize, and in most cases there has not been a clear advantage to early institution of palliative chemotherapy in asymptomatic patients. [read 3 bullets on slide] I’ve seen recommendations, for example, to do CT scans on patients every 6 months after resection of pancreaticobiliary tumors, but I find it hard to even come up with a rationale for that.

Challenges to surveillance research RCTs generally required Lead time & length time biases Large sample size Complex strategy Long duration Improving non-curative treatments Economic evaluation Discounting The problem of a lack of evidence-based recommendations is not an easy one to fix Randomized trials are needed because it’s impossible to control for lead time and length time biases: Detecting relapse earlier will make patients appear to live longer after relapse even if they die on the same day they otherwise would have, and asymptomatic recurrence picked up by testing will tend to be more indolent than ones that are identified because they caused symptoms Because the possible survival benefits are small, the sample sizes need to be large. For example, if, optimistically, 10% of colorectal cancer patients relapse with potentially resectable oligometastatic disease and 1/3 of those can be cured, a study would have to be powered to detect a 3% absolute difference in survival What’s tested in these studies is not as simple as a drug and a placebo, but rather a complex strategy. Consequently, when the studies are negative there’s quibbling about whether the frequency or thresholds of the different components were optimal These are long studies. With patients now living longer after relapse due to advances in palliative treatments, it takes years to reach the endpoint Lastly, even if a strategy is found to improve survival, it may not be deemed cost-effective, because surveillance involves upfront costs for uncertain, future benefits, and so the benefits are discounted in analyses

Rationale for detecting recurrence early Improve survival Improve QoL Psychological reassurance Detect catastrophic complications Enroll in clinical trials Allow patients to plan/put affairs in order The main rationale for detecting recurrence early is to improve survival, however, in most cases there’s not much evidence that we can actually do that We talk about the psychological benefits of being able to reassure patients, but the evidence actually is that follow up visits are extremely stressful for patients and so may increase distress Detecting catastrophic complications of unrecognized recurrence is sometimes cited, things like spinal cord compression or pathological fractures. However, a randomized study done by Eva Grunfeld in Canada showed that patients only followed by their PCP were no more likely to suffer these events than patients followed regularly by oncologists Finding good PS patients with metastatic disease allows them the opportunity to enroll in clinical trials, but the fact that only a few percent of patients are ever treated on clinical trials weakens that argument somewhat One could argue that patients can benefit from knowing that their cancer has recurred and they only have a limited lifespan, in order to allow them to take that trip back to the homeland before they get sick, and maybe it’s paternalistic of us to think that they’re better off not knowing about their recurrence until there’s a symptom or sign. This may be the best rationale in some cases

Risks of overly- aggressive surveillance False positives Mental anguish Harm from invasive testing Cost False negatives There are also risks to surveillance Most surveillance tests don’t give a clear yes or no answer The mildly elevated CEA following a chest cold can cause mental anguish. There can be complications from trying to biopsy a non-specific finding on the resultant scan, and all of this is costly There are also false negatives. In fact, in a patient who eventually relapses, everything we’ve done up until then is a false negative and so we’ve been giving false reassurance to patients

Intensive surveillance beneficial: Testicular Cancer Recurrences are usually within the first 2 yrs Successful salvage exists Therefore, can treat less aggressively; decrease long-term and late effects without compromising cure Hx, Px, markers and imaging every 1-2 months is as effective as upfront treatment with chemotherapy (NSGCT) or radiation (GCT)

Intensive surveillance not beneficial: Breast Cancer Local recurrence and second primaries can be cured Mammography Metastatic disease cannot be cured Two large RCTs of surveillance (& a meta-analysis of them) B/W, chest & abdominal imaging, bone scans No difference in survival or QoL

Intensive surveillance controversial: Colon Cancer Local recurrence uncommon; premalignant polyps common => colonoscopy < 10% relapse with oligometastatic disease ~ 1/3 of those can be cured 6 RCTs unable to demonstrate survival benefit The curable relapses are indolent and would be found anyway? Only urgency for metastases => metastases Meta-analyses suggest CEA and imaging may slightly improve survival If anything, it’s the low-risk patients that benefit ASCO surveillance recommendations

Long-term and late effects

Late medical effects: depend on the type of therapy . . . Surgery Radiation Therapy and the specific toxicities/organ interactions of each therapy Chemotherapy

Common long-term and late effects Surgery Radiation Chemotherapy Cosmesis Functional disability Pain Organ damage Scarring/adhesions Hernia Lymphedema Systemic endocrine, spleen Second malignancies Neurocognitive Dry eyes, cataracts Xerostomia, caries Hypothyroidism CVD, myopathy Pneumonitis/fibrosis Strictures, proctitis Infertility, impotence Bone fractures MDS, AML ‘Chemo brain’ Cardiomyopathy Renal toxicity Menopause Infertility Osteoporosis Neuropathy ASCO guidelines story The Children’s Oncology Group http://www.survivorshipguidelines.org

Dimensions of quality of life affected by cancer Psychological Well Being Control Anxiety Depression Enjoyment/Leisure Fear of Recurrence Cognition/Attention Distress of diagnosis & Treatment Physical wellbeing & Symptoms Functional Ability Strength/Fatigue Sleep & Rest Nausea Appetite Constipation Cancer Survivorship Social Well Being Family Distress Roles & Relationships Affection/Social Function Appearance Enjoyment Isolation Finances Work Spiritual Well Being Meaning of Illness Religiosity Transcendence Hope Uncertainty

Non-cancer care

Most patients diagnosed with cancer today will not die from it Cause of death* % Heart disease 35.5 Stroke 9.9 Lung cancer 4.3 Pneumonia 3.6 Chronic lung disease 3.0 Diabetes 2.5 Heart failure 2.4 Colon cancer 2.2 Ovarian cancer 1.5 *SEER data on breast cancer survivors Story Note that many of these are possibly preventable: Smoking-related medical problems (e.g. lung cancer, COPD), lifestyle-related disorders (obesity & inactivity related to both breast cancer and diabetes), and preventable cancers (colon cancer). This, despite the fact that they all presumably have regular contact with health professionals. Because a breast cancer dx brings patients into the health care system, MDs have the opportunity to intervene. It’s conceivable that looking out for some of these general medical issues may be more important to survival than follow up after primary treatment of the cancer.

Under use of necessary care among cancer survivors (Earle & Neville Under use of necessary care among cancer survivors (Earle & Neville. Cancer 2004;101(8):1712-9) 14,884 5-year colorectal survivors, matched to controls 44 quality of care indicators, divided into acute and chronic care Survivors less likely to receive recommended care for chronic conditions and prevention Despite having more physician visits

Oncologist’s responsibility to screen for other cancers Oncologist’s responsibility to screen for other cancers? (Cheung et al J Clin Oncol 2009) None A little Some A lot Full 7 4 13 30 26 2 6 27 41 39 10 8 44 38 23 28 1 Survivors (n=448) Oncologists

Effect of provider type (Colon cancer survivors)

Getting cancer may be a “teachable moment”

3. Workforce issues

Oncologist Supply  Demand Source: J Clin Practice 2007

At Sunnybrook there are 10,000 1 year follow ups booked

Survivorship care models Oncologist follow up PCP follow up Dedicated survivorship clinics Nurse or PA -led } Shared Care Facilitated by treatment summary and care plan

Shared Care as a Solution Common examples of shared care Coronary artery disease Diabetes HIV infection Chronic renal insufficiency Bipolar disorder Parkinson’s disease Inflammatory bowel disease Seizure disorders NAMCS, 2002

Results – English RCT Randomized Trial Difference Trial Group (95%CI) (18 months follow-up) Trial Group Difference (95%CI) PCP n = 148 Specialist n = 141 Time to diagnosis of recurrence (days) 22 days 21 days 1.5 (-13 to 22) Total time with the patient (min) 35.6 20.7 14.9* (11.3 to18.4) Cost per patient (£s) 65 195 - 130 * (-149 to -112) Time cost to the patient (min) 53 82 - 29 * (-37 to -23) No difference in health-related quality of life over time No difference in anxiety or depression over time PCP patients more satisfied All results at 18 months of follow-up Total of 26 recurrences: 10 in GP group; 16 in hospital group Study was powered to detect a 3month difference in delay at 90% and alpha=0.05 needed 30 recurrences Time with patient” 3.39 visits in GP group; 2.8 visits in hospital group Costs per patient = average cost over 18 months of follow-up per patient (includes costs of visits and costs of tests Time for the patient per appointment = to and from appointment, waiting to see the doctor, with the doctor, does not include costs for the accompanying person. NO difference in deterioration in HRQOL GP patients more satisfied *p<0.001 Grunfeld et al BMJ 1996

Canadian RCT Results Outcome Event PCP (n=483) Specialist (n=485) Risk Difference (95% CI) Number of Patients (%) Recurrence Distant Local Contralateral 54 (11.2%) 36 10 11 64 (13.2%) 38 12 15 2.02% (-2.13, 6.16) Death (All Causes) 29 (6.0%) 30 (6.2%) 0.18% (-2.90, 3.26) Serious Clinical Events 17 (3.5%) 18 (3.7%) 0.19% (-2.26, 2.65) Spinal Cord compression Pathological fracture Uncontrolled local recurrence KPS ≤ 70 Brachial plexopathy Hypercalcemia 3 2 14 1 8 18 Canadian RCT Results Grunfeld et al. JCO 2006

Specialist PCP Mental QoL Physical QoL Specialist PCP

PCP Specialist PCP Specialist

Patient Satisfaction Questionnaire mean scores from baseline to 3 years With respect to the outcome of patient satisfaction, patients in the FP Group were the same at baseline but then significantly more satisfied at each time point with approximately 5 point higher scores. p <0.0001 Number of Responses Specialist 475 439 423 400 389 296 PCP 469 433 411 386 371 277

Colorectal cancer follow-up: Surgeon vs PCP RCT; 203 patients; median follow-up 24 months PCP provided with a guideline Outcomes – quality of life; anxiety; satisfaction - adherence to guideline No difference in primary outcomes PCPs-more frequent visits Surgeon-more frequent imaging and endoscopy Wattchow et al. BJC 2006;94:1116-1121.

Nurse-led models Similar results: No difference in outcomes Satisfaction measures tend to favor nurse-led follow up Brown et al, 2002 Moore et al, 2002 Koinberg et al, 2004 Systematic reviews Cox, 2003 Sheppard, 2004 Lewis, 2009

PCPs are willing to take this on

Barriers to changing the model of survivorship care Doctors adopt a new practice if it is: Obviously better for patients Easier (for them) Remunerated

Summary We’re not meeting our patients’ or our colleagues’ needs in the survivorship phase Simple communication can go a long way towards improving care The quality of care is variable Both overuse and underuse Most survivorship practices not based on evidence Evidence is hard to get There are looming workforce issues Studies show that non-specialist providers can deliver this care Getting physicians to change their model of care is very difficult Some form of shared care is likely the best solution Communication is key to making this work Local care organizations must determine what will work best for them