Chronic Post-Surgical Pain at 3 Months After Breast Cancer Surgery: Incidence, Predictors, and an Internally Validated Risk Model.

Background/Objectives: Chronic post-surgical pain (CPSP) affects 25-60% of women after breast cancer surgery. Prospective data from the Middle East and North Africa (MENA) region remain scarce. This study estimated 3-month CPSP incidence in a Moroccan cohort, developed two internally validated prediction models, and quantified the mediated effects of regional anaesthesia and ketamine through prevention of severe acute postoperative pain. Methods: Prospective cohort of 862 women undergoing curative breast cancer surgery (Institut National d'Oncologie, Rabat; NCT04676438). CPSP was defined as a visual analogue scale (VAS) ≥ 3/10 AND Brief Pain Inventory (BPI) interference ≥ 3/10 at three months. Two logistic regression models were developed (Model A: 7 preoperative variables; Model B: 11 perioperative variables) and internally validated by 1000-bootstrap optimism correction. Counterfactual mediation analysis quantified effects mediated through severe acute pain. Results: CPSP incidence was 39.1% (95% confidence interval (CI) 35.9-42.4%), with 22.6% neuropathic-predominant. Model A showed limited discrimination (area under the curve (AUC) 0.58), with pain catastrophising as the dominant predictor. Model B demonstrated superior performance (AUC 0.694; Brier score 0.209) with net clinical benefit across the 15-55% range of clinically plausible decision thresholds. In counterfactual mediation analysis, an estimated 58.2% and 53.7% of the RA and ketamine effects, respectively, were mediated through severe acute pain, under the framework's no-unmeasured-confounding assumption. Perioperative ketoprofen independently reduced chronification risk (adjusted odds ratio (aOR) 0.66). Conclusions: In this single-centre Moroccan cohort, 39% of women developed CPSP at three months. Two validated models enable risk stratification at distinct clinical decision points. Regional anaesthesia and ketamine were associated with lower CPSP risk, in a pattern consistent with mediation through prevention of severe acute pain under the model's assumptions; ketoprofen was independently associated with lower chronification risk. These observational findings are hypothesis-generating and require confirmation before informing changes to analgesic protocols.