Are older adults adequately represented in surgical oncology trials?

Surgeons are no strangers to the elderly. As baby boomers age, older patient populations are becoming the norm for surgeons’ day-to-day practice. Recent estimates project that 20 percent of the U.S. population will be older than 65 years of age by 2030, and 70 percent of cancers and 85 percent of cancer-related deaths will occur in this population.1 As this generation ages, the question becomes, “Are we equipped with the evidence necessary to optimize the care of this growing population? Are we getting enough information from clinical trials?”

Gap between cancer trials and the real world

To date, randomized clinical trials have been critical to the everyday practice of surgery by providing high-quality evidence that can be used to guide and establish the standards of treatment for cancer patients. In most cancer trials, enrollees are young, healthy, carefully selected, and closely monitored. However, outside these defined settings, the ability to apply the results of cancer trials to older patients has been called into question.2-5 Whereas more than 65 percent of solid malignant tumors were diagnosed in older persons (older than 65 years), their enrollment fraction to surgical oncology trials remained profoundly low (0.14 percent–0.45 percent).4 Thus, the National Cancer Institute (NCI) has established federal policies and initiatives to encourage investigators to enroll a broader range of patients with cancer in clinical trials.2-3,6-8 Furthermore, age has become an important consideration in treatment decisions for cancer patients and their clinicians in this era of personalized medicine.

To assess the impact of federal policies on accrual patterns to cancer trials overall, our group examined patterns and predictors of enrollment in clinical trials for stage 0–IV solid organ malignant tumors within the California Cancer Registry.9 Less than 1 percent of the patients enrolled in cancer trials. Older individuals were less likely to be enrolled into cancer trials.9 Given the widening gap between the efficacy of cancer trials versus their effectiveness in real-world practice, we also assessed the overall implementation of guideline-recommended cancer care of various solid cancer sites in the U.S. in relation to demographics, including age, race, ethnicity, and geographic location. Consistently, we found that older people, ethnic minorities, and rural patients were less likely to receive guideline-recommended cancer care.9-11

Study examines accrual patterns

Based on recent findings as noted earlier in this article, Z901101 is under way to closely assess accrual patterns and drop rates of older adults within a large cohort of surgical oncology trials. To gain additional insights into accrual patterns of the American College of Surgeons Oncology Group (ACOSOG), we initially compared the age distribution of individuals enrolled in select ACOSOG gastrointestinal cancer studies with the real-world setting of cancer patients, including patients at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) and NCI tumor registries (see table). Fewer older adults were enrolled in ACOSOG gastrointestinal trials in comparison with those in real-world settings. Upon completion and after adjusting for other important clinical factors, we anticipate that these preliminary comparisons will show poorer enrollment patterns across other cancer sites.

Table 1. Age distributions of enrollees to ACOSOG protocols versus other settings

Impact on the real world

The overarching goal of Z901101 is to improve surgeons’ understanding of current barriers to accrual of older adults into surgical oncology trials and to engage more surgeons in these trials. It is anticipated that Z901101 will inform future research strategies and policies in the following domains:

  1. Development of future surgical oncology trials reflective of real-world experience and cancer burden distribution in the community (that is, the distribution of older adults in a new trial should match their distribution in the community).
  2. Identification and mitigation of underlying factors at the level of patients, surgeons, and hospitals behind these anticipated low accrual rates in surgical oncology trials.
  3. Aggressive efforts to include large health care systems, nonacademic centers, and Veterans Affairs hospitals through engagement of their surgeons who care for older patients in order to add heterogeneity to the study of performance status and comorbidities.
  4. Continued assessment of whether the effectiveness of surgical oncology trials extends to a growing population of older persons. If so, we will seek to identify a subset of those within whom this benefit is observed. For example, would the benefit of perioperative systemic therapy for operable pancreatic cancer trials translate into a similar benefit in older persons in the real world?

In closing, older adults are projected to comprise a significant portion of a surgeon’s patient population. However, current surgical oncology trials are not designed to allow for widespread generalizability to their practice. Upon completion, Z901101 aims to shed additional insights into underlying barriers and stimulate future studies and policies to broaden the accrual of older adults and their surgeons in future surgical oncology trials.


References

  1. Jemal A, Ward E, Hao Y, Thun T. Trends in the leading causes of death in the United States, 1970-2002. JAMA. 2005;294(10):1255-1259.
  2. Al-Refaie WB, Vickers SM. Are cancer clinical trials valid and  useful for the general surgeon and surgical oncologist? Adv Surg. 2012;46:269-281.
  3. Al-Refaie WB, Pisters PW, Rothenberger DA. Surgical oncology trials and surgeons in the real world! Ann Surg Oncol. 2010;17(7):1727-1728.
  4. Stewart JH, Bertoni AG, Staten JL, Levine EA, Gross CP. Participation in surgical oncology clinical trials: Gender-, race/ethnicity-, and age-based disparities. Ann Surg Oncol. 2007;14(12):3328-3334.
  5. Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr., Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061-2067.
  6. Herrera A, Snipes SA, King DW, Torres-Vigil I, Goldberg DS, Weinberg AD. Disparate inclusion of older people into clinical trials: Priorities and opportunities for policy and practice change. Am J Public Health. 2010;100:S100-108.
  7. Baylor College of Medicine. Eliminating disparities in clinical trials. Brief explanation of proposed questions. Available at: http://lifebeyondcancer.org/edict/EDICT_Model_Checklist_for_Editors_and_Staff_of_Journals_
    Publishing_Clinical_Trials_Data.pdf
    . Accessed March 27, 2013.
  8. Newman LA, Hurd T, Leitch M,  Kuerer HM, Diehl K, Lucci A, Giuliano A, Hunt KK, Putnam W, Wells SA. A report on accrual rates for elderly and minority-ethnicity cancer patients to clinical trials of the American College of Surgeons Oncology Group. J Am Coll Surg. 2004;199(4):644-651.
  9. Al-Refaie WB, Vickers SM, Zhong W, Parsons HM, Rothenberger DA, Habermann EB. Cancer trials versus the real world. Ann Surg. 2011;254(3):438-442.
  10. Al-Refaie WB, Habermann EB, Dudeja V, Vickers SM, Tuttle TM, Jensen EH, Virnig BA. Extremity soft tissue sarcoma care in the elderly: Insights into the generalizability of NCI Cancer Trials. Ann Surg Oncol. 2010;17(7):1732-1738.
  11. Dudeja V, Habermann EB, Zhong W,  Tuttle TM, Vickers SM, Jensen EH, Al-Refaie WB. Guideline recommended gastric cancer care in the elderly: Insights into the applicability of cancer trials to real world. Ann Surg Oncol. 2011;18(1):26-33.

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