{'fraction_non_alphanumeric': 0.02364066193853428, 'fraction_numerical': 0.014184397163120567, 'mean_word_length': 5.280701754385965, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Reducing Harms in Lung Cancer Screening-Bach to the Future.

The US Preventative Services Task Force currently recommends screening (grade B recommendation) for lung cancer with annual low-dose computed tomography for high-risk individuals ages 55 to 80 years, defined as those having greater than a 30 pack-year cumulative smoking history and having quit within the past 15 years.1 The evidence to support this recommendation overwhelmingly comes from the National Lung Cancer Screening Trial (NLST). While 3 other large randomized clinical trials failed to show any mortality benefit to lung cancer screening (LCS), the NLST demonstrated a 20% reduction in lung cancer mortality, along with a 6.7% reduction in all-cause mortality, when compared with an annual chest radiograph, with a number needed to screen (NNS) of 256 to prevent 1 lung-cancer associated death over 3 years.2-5 Real-world application of LCS has been particularly challenging, with evidence of inappropriate use in low-risk persons along with very high rates of incidental findings and falsepositive results leading to a much higher harm to benefit ratio than what was seen in randomized clinical trials.2-7 The most robust implementation data to date, conducted on a large highrisk population through the Veterans Health Administration system, demonstrated that 56% of those screened had nodules requiring follow-up with repeated imaging and/or invasive procedures, and 40% had incidental findings, such as emphysema and coronary artery calcification, with a relatively low cancer detection rate of 1.5% (even lower for early-stage cancers that most benefit from screening).6 Increasingly, there has been concern about both the cost-effectiveness of LCS and the harms associated with screening, including high rates of incidental findings (resulting in unnecessary invasive procedures and emotional stress), as well as radiation exposure (possibly leading to secondary malignant neoplasm.7-9 These findings raise the question of whether a more targeted inclusion criteria may decrease the total number of patients screened and the false-positivity rate without sacrificing the mortality benefit seen in the NLST. It is against this background that Caverly et al10 examine the impact of risk stratifying a real-world cohort of patients eligible for LCS using the Bach risk tool,11 a validated risk model using sex, age, smoking duration, duration of abstinence from smoking and number of cigarettes smoked per day as inputs. The astoundingly high rates of false-positive results in the lowest risk quintiles (eg, 2221 false-positive results per lung cancer death averted and a NNS of nearly 5600 in quintile 1), as well as extremely low rates of lung cancer incidence in the lowest-risk groups, confirm trends illustrated in previous studies and make the case for refined guidelines for LCS.12,13 This is especially salient in light of recent evidence suggesting that high numbers of low-risk individuals are being screened in realworld practice.7 Unfortunately, the use of LDCT screening even in the highest-risk quintiles is still associated with alarmingly high rates of false-positive results—302 false-positive results for every lung cancer death prevented (NNS, 552), in addition to high rates of incidental findings potentially requiring intervention as noted in the original cohort study.6 Furthermore, while the authors correctly point out large differences in screening efficacy and benefit to risk ratio between the highest and lowest risk quintiles, the data are murkier in between, with greater than 500 false-positive results per lung cancer death prevented for all but the highest-risk quintile, meaning that most participants are exposed to an unfavorable benefit to risk ratio. Caverly et al10 have made the important contribution of applying a validated risk stratification tool to a real-world cohort to improve screening criteria. Other groups have retrospectively demonstrated reduced harms in study populations with novel risk stratification tools using easily obtainable patient information, such as emphysema diagnosis, smoking history, age, sex, and family history.12,13 However, clearly more work is needed to minimize the harms of radiation exposure, invasive procedures, and emotional stress under current guidelines, while preserving benefit for those whose lives could be saved by the early detection of lung cancer. If and how we will get there has yet to be determined, but one thing is clear: the future of LCS depends on our ability to reexamine and refine our approach to patient selection and clearly communicate risks and benefits of screening.