Standard versus pH-adjusted and lidocaine supplemented radiocolloid for patients undergoing sentinel-lymph-node mapping and biopsy for early breast cancer (PASSION-P trial): a double-blind, randomised controlled trial

Background: Sentinel-lymph-node (SLN) mapping and biopsy maintains staging accuracy in early breast cancer and identifies patients for selective lymphadenectomy. SLN mapping requires injection of technetium-99m-sulfur colloid-an effective but sometimes painful method, for which better pain-management strategies are needed. In this randomised, double-blind trial, we compared degree of pain between standard radiocolloid injection and pH-adjusted and lidocaine-supplemented formulations for patients undergoing SLN mapping for breast cancer. Methods: Between Jan 13, 2006, and April 30, 2009, 140 patients with early breast cancer were randomly assigned in a 1:1:1:1 fashion to receive the standard topical 4% lidocaine cream and injection of [^99mTc]Tc-sulfur colloid (n=35), or to one of three other study groups: topical placebo cream and injection of Tc-sulfur colloid containing either sodium bicarbonate (n=35), 1% lidocaine (n=35), or sodium bicarbonate and 1% lidocaine (n=35). The randomisation sequence was computer generated, and all patients and investigators were masked to treatment allocation. The primary endpoint was patient-reported breast pain immediately after radioisotope injection, using the Wong-Baker FACES pain rating scale and McGill pain questionnaire, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT00940199. Findings: 19 of the 140 patients enrolled were excluded from analysis: nine declined study participation or sought care elsewhere, nine did not undergo SLN mapping because of disease extent or a technical problem, and one had unreliable data. There were no adverse events. Mean pain scores on the Wong-Baker scale (0-10) were: 6·0 (SD 2·6) for those who received standard of practice, 4·7 (3·0) for those who received radiocolloid plus bicarbonate, 1·6 (1·4) for those who received radiocolloid plus 1% lidocaine, and 1·6 (1·3) for those who received radiocolloid plus bicarbonate and 1% lidocaine (p<0·0001). Mean pain rating, according to the McGill questionnaire (0-78), was 17·5 (SD 11·8) for the standard-of-care group, 15·4 (14·4) for the sodium bicarbonate group, 4·6 (4·5) for the 1% lidocaine group, and 3·4 (5·1) for the sodium bicarbonate plus 1% lidocaine group (p<0·0001). SLN identification rates for each group were: 96% for the standard of care, 97% for sodium bicarbonate, 90% for 1% lidocaine, and 90% for sodium bicarbonate plus 1% lidocaine group (p=0·56). Interpretation: For centres that use radiocolloid injections for SLN mapping in patients with early breast cancer, the addition of 1% lidocaine to the radioisotope solution can improve patient comfort, without compromising SLN identification. Funding: US Military Cancer Institute, the Clinical Breast Care Project, and the Army Regional Anesthesia and Pain Management Initiative.