Pre-treatment optimization with pulmonary rehabilitation in lung cancer: Making the inoperable patients operable.

Background: Anatomical lung resection offers the best prospect of long-term survival in patients with non-small cell lung cancer (NSCLC). However, some patients with significant dyspnoea, impaired performance status (PS), borderline or poor pulmonary function are considered inoperable and instead referred for radiotherapy, chemotherapy or palliative care. The aims of the study were to determine whether pre-operative pulmonary physiotherapy (Prehab), by improving clinical parameters, (i) makes patients suitable for surgery who were considered inoperable on subjective criteria of dyspnoea >3 and PS >2, and objective criteria of diffusing capacity for carbon monoxide (DLCO) <50%; and (ii) thereby allows them to safely receive curative surgery with reduced morbidity and mortality.

Methods: From January 2017 to December 2018 a total of 306 patients were prospectively and sequentially assessed for Prehab and 216 patients with lung cancer studied. Their mean age (95% CI) was 71.7 ± 1.1 years, 50.5% ( = 109) were men and they received Prehab over 39.0 ± 7.0 days averaging 3.1 ± 0.6 sessions. Their dyspnoea scores, PS, level of activity, six minute walk test (6MWT) and frailty index prior to and following Prehab were determined. Following surgery the post-operative length of hospital stay (LOHS), complications and mortality at 30 days, 90 days and 1 year determined. Similar outcomes were determined for (i) high-risk patients with dyspnoea scores >3 and PS >2, and compared with low-risk patients having dyspnoea scores <2 and PS <2 (subjective criteria); and (ii) high-risk patients with DLCO <50% and compared with low-risk patients with DLCO >80% (objective criteria).

Findings: In the total cohort following Prehab, there was significant improvement in the dyspnoea scores <2 / ≥2 (40%/60% prior to Prehab vs. 65%/35% following Prehab,  = 0.00002), PS <2 / ≥2 (45%/55% prior to vs. 62%/38% following Prehab,  = 0.003), frailty index ≤3 / >3 (49%/51% vs 70%/30%,  = 0.0006), and 6MWT (306.6 ± 6.8 m vs 354.8 ± 52.7 m,  = 0.04). Post-operative major complication rates were 8.7%; median LOHS was 7 (IQR 6) days; hospital mortality at 30 days 1.3%, 90 days 4.7% and 1 year 16%. Using subjective criteria of dyspnoea scores >3 and PS >2, 100% of high-risk patients were considered inoperable. Following optimization with Prehab 84.2% of the high-risk patients were ready to proceed with radical treatment and 52.6% with surgery, and subsequently 42.8% of patients underwent surgery. Likewise, 78.8% of patients with DLCO <50% were considered inoperable. Following Prehab 86.5% of high-risk patients were ready to proceed with radical treatment and 59.1% with surgery, and 54.6% of high-risk patients underwent surgery. In each category there were no significant differences in complications, LOHS or mortality rates between the high-risk and low-risk patients.

Interpretation: Our prospective study showed that with Prehab there was clinical and statistically significant improvement in the dyspnoea scores, PS, level of activity and frailty, particularly in the high-risk group of patients. Importantly, Prehab made previously inoperable patients operable, allowing them to safely undergo curative lung resection. This strategy helps improve resection rates and may contribute to the long term survival of lung cancer patients.

Funding: This is a Welsh Health Specialised Services Committee (WHSSC) commissioned service.