Challenges in the treatment of early non-small cell lung cancer: what is the standard, what are the challenges and what is the future for radiotherapy?

In the last 15 years, the use of Stereotactic Ablative Radiation Therapy (SABRT) in the management of small peripheral lung tumours has developed considerably, so that it currently represents a standard of care for inoperable stage I non-small cell lung cancer (NSCLC), offering a survival advantage over traditional radiotherapy, local control rates at 3 years around 90%, with a low risk of toxicity. Indications have extended to larger tumours up to 5 cm and centrally located tumours. In this review we will explore the role of SABRT in early stage NSCLC, the state of the art, the challenges and the future for this technique. There are ongoing studies to optimize such approaches within a multicentric setting. Trials comparing surgery to SABRT in operable or marginally operable have failed because of poor accrual. Several questions remain that need to be addressed in prospective studies.

Role of adjuvant radiotherapy in completely resected non-small-cell lung cancer.

Most long-term survivors of non-small-cell lung cancer (NSCLC) are patients who have had a completely resected tumour. However, this is only achievable in about 30% of the patients. Even in this highly selected group of patients, there is still a high risk of both local and distant failure. Adjuvant treatments such as chemotherapy (CT) and radiotherapy (RT) have therefore been evaluated in order to improve their outcome. In patients with stage II and III, administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of postoperative radiation therapy (PORT) remains controversial. In the PORT meta-analysis published in 1998, the conclusions were that if PORT was detrimental to patients with stage I and II completely resected NSCLC, the role of PORT in the treatment of tumours with N2 involvement was unclear and further research was warranted. Thus at present, after complete resection, adjuvant radiotherapy should not be administered in patients with early lung cancer. Recent retrospective and non-randomised studies, as well as subgroup analyses of recent randomised trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT needs to be evaluated also for patients with proven N2 disease who undergo neoadjuvant chemotherapy followed by surgery. The risk of local recurrence for N2 patients varies between 20% and 60%. Based on currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy or after surgery if patients have had preoperative chemotherapy. There is a need for new randomised evidence to reassess PORT using modern three-dimensional conformal radiation technique, with attention to normal organ sparing, particularly lung and heart, to reduce the possible over-added toxicity. Quality assurance of radiotherapy as well as quality of surgery - and most particularly nodal exploration modality - should both be monitored. A new large multi-institutional randomised trial Lung ART evaluating PORT in this patient population is needed and is now under way.