Local treatment of colorectal pulmonary metastases

In this thesis the role of local therapy for pulmonary oligometastases in colorectal cancer patients is described. In the introduction, Chapter 1, the theory and basis for the oligometastatic state are explained, including the rationale behind the organ-specific pattern and distribution of metastatic disease. The randomized trials supporting the presence of an oligometastatic state are noted, and a review is presented of the landmark studies that have been performed on the use of local radical-intent treatment for patients with colorectal liver and lung metastases. In Chapter 2, data is used from the Dutch Lung Cancer Audit for Surgery (DLCA-S) on all patients that underwent a metastasectomy for lung metastases in the Netherlands from 2012 to 2017. It shows that 52.0% of resections are performed for colorectal cancer metastases. Analysis of surgical outcomes demonstrated a complicated postoperative course in 3.6% of patients, and a 30-day mortality rate of 0.7%. The group of Tom Treasure presented a Letter to the Editor based on the publi- cation of the DLCA-S metastasectomy outcome, as presented in Chapter 2. In Chapter 3, we comment on this letter and provide a review of the outcome of the PulMiCC trial, the SABR-COMET trial, and the CLOCC trial. We debate the validity of using both local and systemic treatment options for oligometastatic disease. While presenting important limitations of the aforementioned trials. Chapter 4 contains the largest ever published survival analysis on patients following metastasectomy for colorectal pulmonary metastases (CRPM), while also presenting a comparative analysis with repeat metastasectomy. We present a five-year survival of 52% after metastasectomy and 53% for repeat metas- tasectomy. Multivariable Cox regression analyses demonstrated Eastern Coop- erative Oncology Group performance status, multiple metastases, and bilateral metastases as poor prognostic factors for overall survival. A survey on metastasectomy for CRPM was performed of all members of the European Society of Thoracic Surgeons , and the results are presented in Chapter 5. In total, 308 complete responses were received (response rate: 22%) from 62 countries. Most respondents consider that metastasectomy improves disease control (97%) and improves patients’ survival (92%). Criteria for resectability vary, and controversy remains regarding lymph node assessment and the role of adjuvant systemic therapy. In Chapter 6, a systematic review is presented on lymphadenectomy during metastasectomy for CRPM. A total of 690 patients (19.1%) had simultaneous lymph node metastases. Five-year overall survival for patients with and without lymph node metastases was 18.2% and 51.3%, respectively (p < 0.001). Five-year overall survival for patients with N1 and N2 lymph node metastases was 40.7% and 10.9%, respectively (p = 0.064). In Chapter 7, the institutional data of the Amsterdam University Medical Center on SABR, and the Máxima Medical Center on metastasectomy for CRPM from 2012 to 2019 were compared. The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group comprised 60 patients treated for 90 metastases. Metastasectomy and SABR had similar overall survival, local recurrence-free survival and complication rate, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. Chapter 8 contains the largest ever published series on salvage surgery for patients with local recurrence following SABR for CRPM and includes 17 patients with 20 salvage resections. The median overall survival and progression-free survival following salvage resection were 71 months (CI: 50 – 92) and 39 months (CI: 19 – 58), respectively. Chapter 9 contains the discussion and future perspectives on the local treatment of colorectal pulmonary metastases and presents the design for a new randomized controlled trial.