TOPLINE:

Among survivors of non-small cell lung cancer (NSCLC), 7.9% developed non-lung secondary cancers, and 13.5% had a recurrence over a median follow-up of nearly 6 years. The 5-year cumulative incidence with competing risks for non-lung secondary cancer was 5.6% vs 11.5% for NSCLC recurrence. The presence of certain genetic factors was associated with a higher risk for non-lung secondary cancers.

METHODOLOGY:

• Survivors of NSCLC face ongoing risks for recurrence and second primary cancers, but data on the incidence, timing, and outcomes of non-lung secondary cancers remain limited.
• Researchers assessed 496 consecutive survivors of stage I-III NSCLC (median age, 69.1 years) who were treated with curative-intent local therapy and evaluated in a dedicated survivorship clinic at a single high-volume academic cancer center from January 2019 to May 2019.
• Study outcomes included the incidence and timing of recurrence, non-lung secondary cancers, and death. The median follow-up duration from completion of local therapy was 71.6 months.
• Overall, 67.9% of patients had stage I, 14.5% had stage II, and 17.5% had stage III cancer; 74.0% were former smokers, and 75.0% had adenocarcinoma.

TAKEAWAY:

• Overall, 13.5% of patients (67 of 496) experienced NSCLC recurrence. Secondary cancers developed in 23.4% of patients (116 of 496) — new primary lung cancers in 15.5% and non-lung secondary cancers in 7.9%. The median time to the first documented recurrence was 31.5 months, and the median time to the diagnosis of a non-lung secondary cancer was 52.3 months.
• The 5-year cumulative incidence with competing risks was 5.6%; this cumulative incidence was 11.5% for NSCLC recurrence.
• The most frequent non-lung secondary cancers were breast (15.4%), prostate (12.8%), pancreatic (12.8%), and head and neck (12.8%). Among those with non-lung secondary cancers, 69.2% were symptom-detected, 30.8% were incidental, and none were first identified through population screening. The 2-year overall survival after diagnosis was 73.3%, and 20.5% of patients presented with metastatic disease.
• In multivariable models, having a hereditary syndrome and/or pathogenic germline variant was associated with a significantly higher risk for non-lung secondary cancer (subdistribution hazard ratio [SHR], 10.76; P < .001). However, cumulative smoking exposure, measured in pack‑years and evaluated per 10-pack‑year increase, was not associated with a higher risk for non-lung secondary cancer (SHR per 10 pack-years, 1.00; P = .85).

IN PRACTICE:

The findings support a “pragmatic, risk-adapted survivorship approach that includes maintaining guideline-concordant thoracic imaging, incorporating brief hereditary-risk assessment with genetics referral when indicated, coordinating age-appropriate population screening, and keeping a low threshold to evaluate new extrathoracic symptoms,” the study authors said.

SOURCE:

The study, led by Matthew McMillan, MD, Memorial Sloan Kettering Cancer Center, New York City, was published online in JAMA Network Open.

LIMITATIONS:

The cohort was drawn from a single academic survivorship clinic that typically transitioned patients who were disease-free approximately 24 months after therapy, which enriched the cohort for stage I disease and may have limited generalizability. The study lacked reliable data on the total number of treated non-NSCLC patients during accrual, preventing estimation of referral or transition rates. Additionally, visit and imaging adherence were not consistently documented in structured fields, which may have influenced detection timing.

DISCLOSURES:

The authors of the study did not declare any funding information. Several authors reported receiving grants or personal fees and having other ties with various sources. Full disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.