Sizing up Testicular Masses: Clinical Implications of Lesion Size and Contralateral Biopsy

Background/Objectives: Accurate preoperative discrimination between benign and malignant testicular masses remains challenging. Lesion size has been suggested as a predictor, but robust cutoffs and the role of contralateral biopsy remain uncertain. Methods: We retrospectively analyzed a prospectively maintained single-center database of 387 patients treated for testicular lesions between December 2013 and November 2024. Patients with malignant non-germ cell histologies or prior systemic GCT therapy were excluded. Lesion size was evaluated as a predictor of malignancy using ROC analysis, logistic regression, and predefined cutoffs (5, 8, 10, 15 mm). Associations between contralateral biopsy results and clinical variables were assessed using uni- and multivariable analyses. Results: Of 387 patients, 284 (73.4%) had malignant GCTs. Malignant lesions were significantly larger than benign ones (median 25.0 vs. 5.5 mm, p < 0.001). Lesion size showed good discrimination between benign and malignant lesions (AUC 0.829, 95% CI 0.784-0.874), with a Youden-derived optimal cutoff of 12.5 mm. Internal bootstrap validation (2000 resamples) yielded a median optimal cutoff of 12.5 mm (95% percentile interval 7.45-19.5 mm), indicating uncertainty regarding the exact threshold. Among 360 patients with complete clinical and tumor-marker data, combining lesion size with age, AFP, β-HCG, and LDH significantly improved discrimination compared with lesion size alone (AUC 0.863 vs. 0.818; DeLong p = 0.003). Contralateral biopsy was performed in 249 patients, with 7 (2.8%) positive for GCNIS. Younger age was associated with contralateral GCNIS, while tumor size, serum markers, and histology were not predictive. Multivariable analysis showed no significant predictors. Conclusions: Lesion size is a strong predictor of malignant histology, although the optimal size threshold remains subject to uncertainty. Combining lesion size with readily available clinical and biochemical parameters may further improve preoperative risk stratification. Contralateral GCNIS was rare and not reliably predicted, supporting individualized biopsy strategies.