Deep learning methods provide enormous promise in automating manually intense tasks such as medical image segmentation and provide workflow assistance to clinical experts. Deep neural networks (DNN) require a significant amount of training examples and a variety of expert opinions to capture the nuances and the context, a challenging proposition in oncological studies (H. Wang et al., Nature, vol. 620, no. 7972, pp. 47-60, Aug 2023). Inter-reader variability among clinical experts is a real-world problem that severely impacts the generalization of DNN reproducibility. This study proposes quantifying the variability in DNN performance using expert opinions and exploring strategies to train the network and adapt between expert opinions. We address the inter-reader variability problem in the context of prostate gland segmentation using a well-studied DNN, the 3D U-Net model. Reference data includes magnetic resonance imaging (MRI, T2-weighted) with prostate glandular anatomy annotations from two expert readers (R#1, n = 342 and R#2, n = 204). 3D U-Net was trained and tested with individual expert examples (R#1 and R#2) and had an average Dice coefficient of 0.825 (CI, [0.81 0.84]) and 0.85 (CI, [0.82 0.88]), respectively. Combined training with a representative cohort proportion (R#1, n = 100 and R#2, n = 150) yielded enhanced model reproducibility across readers, achieving an average test Dice coefficient of 0.863 (CI, [0.85 0.87]) for R#1 and 0.869 (CI, [0.87 0.88]) for R#2. We re-evaluated the model performance across the gland volumes (large, small) and found improved performance for large gland size with an average Dice coefficient to be at 0.846 [CI, 0.82 0.87] and 0.872 [CI, 0.86 0.89] for R#1 and R#2, respectively, estimated using fivefold cross-validation. Performance for small gland sizes diminished with average Dice of 0.8 [0.79, 0.82] and 0.8 [0.79, 0.83] for R#1 and R#2, respectively.