Evaluating the Relationship Between Cancer Stage and Mortality Endpoints in Screening Trials

Core Concepts

Late-stage cancer incidence may be a suitable alternative endpoint to cancer-specific mortality in lung and ovarian cancer screening trials, but not in breast, colorectal, or prostate cancer screening trials.

Abstract

The study assessed the relationship between reductions in the incidence of late-stage (stage III or IV) cancer and reductions in cancer-specific mortality as endpoints in cancer screening trials. The researchers conducted a meta-analysis of 41 randomized controlled trials that examined screening for various cancer types, including breast, colorectal, lung, ovarian, and prostate cancer.
The key findings are:

Overall, the correlation between the effects of cancer screening on cancer-specific mortality and stages III-IV cancer incidence varied across trials and by cancer type.
The correlation was strongest for ovarian cancer (Pearson ρ = 0.99) and lung cancer (Pearson ρ = 0.92), indicating that late-stage cancer incidence may be a suitable alternative endpoint to cancer-specific mortality in these cancer screening trials.
The correlation was moderate for breast cancer (Pearson ρ = 0.70) and weak for colorectal cancer (Pearson ρ = 0.39) and prostate cancer (Pearson ρ = -0.69), suggesting that late-stage cancer incidence is unlikely to be a suitable alternative endpoint to cancer-specific mortality in screening trials for these cancer types.
The authors concluded that in screening trials evaluating multicancer early detection tests, using late-stage cancer incidence as an endpoint instead of cancer mortality "is likely to be invalid."

Stats

"Overall, the correlation between the effects of cancer screening on cancer-specific mortality and stages III-IV cancer incidence varied across trials and by cancer type."
"Five trials (12%) found that the specific screening modality under investigation was associated with a reduction in cancer mortality and incidence of stages III-IV cancer; 24 trials (59%) did not demonstrate a reduction in either."
"In eight trials (20%), screening demonstrated reductions in stages III-IV cancer incidence but not cancer mortality, and in four trials (10%), the opposite occurred."

Quotes

"For clinical trials that screen for lung and ovarian cancers, incidence of stage III-IV cancer may be a suitable alternative endpoint to cancer-specific mortality."
"Stage III-IV cancer incidence is unlikely to be a suitable alternative endpoint to cancer-specific mortality in screening trials for breast, colorectal, and prostate cancers."
"Cancer-related mortality remains the most appropriate endpoint for clinical evaluation of the new blood-based tests that aim to detect many cancers for which there is no evidence that screening is beneficial."

Key Insights Distilled From

Cancer Stage vs Mortality Endpoints in Screening Trials?

by Megan Brooks at www.medscape.com 04-18-2024

https://www.medscape.com/viewarticle/cancer-stage-vs-mortality-endpoints-screening-trials-whats-2024a10007id

Deeper Inquiries

What factors may contribute to the varying correlation between late-stage cancer incidence and cancer-specific mortality across different cancer types?

The varying correlation between late-stage cancer incidence and cancer-specific mortality across different cancer types can be influenced by several factors. One key factor is the natural history of the specific cancer type. For instance, some cancers may progress more rapidly from early to late stages, leading to a stronger correlation between late-stage incidence and mortality. On the other hand, certain cancers may have a longer latency period, where late-stage diagnosis does not necessarily translate to immediate mortality, affecting the correlation.
Additionally, the effectiveness of screening modalities for each cancer type plays a crucial role. If a screening test is more sensitive in detecting early-stage cancers for a particular type, it may lead to a weaker correlation between late-stage incidence and mortality. Moreover, the availability and efficacy of treatment options for different cancers can impact the correlation. Cancers with more effective treatments at late stages may show a weaker correlation compared to those with limited treatment options.
Furthermore, the heterogeneity in tumor biology, aggressiveness, and metastatic potential among different cancer types can contribute to the varying correlation. Some cancers may have a higher propensity for metastasis even at early stages, affecting the relationship between late-stage diagnosis and mortality. Overall, a combination of these factors and the complex interplay between cancer characteristics, screening methods, and treatment outcomes can lead to the observed variations in correlation across cancer types.

How can the findings of this study inform the design and evaluation of future multicancer early detection screening trials?

The findings of this study can provide valuable insights for the design and evaluation of future multicancer early detection screening trials. Firstly, the study highlights the importance of selecting appropriate endpoints based on the specific cancer type being studied. For cancers like lung and ovarian, where late-stage cancer incidence correlates strongly with cancer-specific mortality, using late-stage incidence as an endpoint may be suitable. In contrast, for breast, colorectal, and prostate cancers, where the correlation is weaker, focusing on cancer-specific mortality as the primary endpoint is more appropriate.
In designing future multicancer screening trials, researchers can consider tailoring the endpoint selection based on the characteristics of the cancers under investigation. Understanding the relationship between late-stage cancer and mortality for each cancer type can help in determining the most relevant and informative endpoint for assessing screening efficacy. This targeted approach can lead to more efficient trial designs and more accurate evaluation of screening interventions.
Moreover, the study emphasizes the need for comprehensive evaluation of screening outcomes beyond just late-stage cancer and mortality. Future trials could incorporate additional measures such as quality of life, cost-effectiveness, overdiagnosis rates, and treatment outcomes to provide a holistic assessment of the effectiveness of screening interventions. By considering the nuanced differences in correlation between cancer types and endpoints, researchers can optimize the design and evaluation of multicancer early detection screening trials for improved clinical decision-making.

What other endpoints or measures, beyond cancer stage and mortality, could be considered to assess the effectiveness of cancer screening interventions?

In addition to cancer stage and mortality, several other endpoints and measures could be considered to assess the effectiveness of cancer screening interventions. One important measure is the detection rate of early-stage cancers, which reflects the screening test's ability to identify cancers at a curable stage. High detection rates of early-stage cancers indicate the efficacy of the screening modality in detecting tumors before they progress to advanced stages.
Another valuable endpoint is the rate of interval cancers, which are cancers diagnosed between scheduled screening rounds. Monitoring interval cancer rates can provide insights into the screening test's sensitivity and the effectiveness of the screening program in detecting cancers that may have been missed during regular screenings.
Furthermore, considering patient outcomes such as survival rates, recurrence rates, and treatment response can offer a comprehensive assessment of the impact of screening on long-term cancer outcomes. Evaluating the quality-adjusted life years (QALYs) gained from screening can help weigh the benefits of early detection against potential harms like overdiagnosis and overtreatment.
Cost-effectiveness analyses are also essential endpoints to consider, as they assess the economic implications of implementing screening programs and can guide resource allocation decisions. Patient-reported outcomes, including anxiety levels, satisfaction with screening experience, and adherence to follow-up recommendations, can provide valuable insights into the psychological and behavioral impacts of screening interventions.
By incorporating a diverse set of endpoints and measures beyond cancer stage and mortality, researchers can capture the multidimensional effects of cancer screening interventions and make more informed decisions regarding their implementation and effectiveness.