A Novel Nomogram Provides Improved Accuracy for Predicting Biochemical Recurrence After Radical Prostatectomy

A Novel Nomogram Provides Improved Accuracy for Predicting Biochemical Recurrence After Radical Prostatectomy

Prostate cancer remains one of the most prevalent cancers and the second leading cause of cancer-related mortality in men. Radical prostatectomy (RP) is a common treatment for localized prostate cancer. However, a significant proportion of patients, ranging from 20% to 30%, experience biochemical recurrence (BCR) after RP. BCR is defined as a post-operative prostate-specific antigen (PSA) value greater than 0.20 ng/mL in two consecutive measurements. Accurate prediction of BCR is crucial for guiding post-operative management and decision-making regarding adjuvant therapies.

Various prediction tools have been developed to estimate the risk of BCR after RP. These tools typically incorporate clinical and pathological parameters such as pre-operative PSA levels, Gleason score, tumor stage, surgical margin (SM) status, extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). One of the most widely used tools is the Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) score, which has demonstrated good discriminative accuracy and calibration. However, few existing prediction models incorporate both maximum tumor diameter (MTD) and post-operative PSA nadir, despite evidence suggesting their prognostic value in predicting BCR.

This study aimed to develop a novel nomogram that incorporates MTD measured on magnetic resonance imaging (MRI) and PSA nadir, along with other conventional predictors, to improve the accuracy of BCR prediction after RP. The study retrospectively analyzed data from 337 patients who underwent RP between January 2010 and March 2017 at Peking University Third Hospital. Patients with neoadjuvant therapy, prior transurethral resection of the prostate, unidentifiable lesions on MRI, non-adenocarcinoma pathology, or incomplete follow-up data were excluded.

The MTD was defined as the largest diameter of the index lesion on axial T2-weighted MRI images. For multifocal cases, only the largest tumor nodule was measured. PSA nadir was defined as the lowest PSA level recorded within the first two follow-ups after RP, without adjuvant androgen deprivation therapy or radiotherapy. BCR-free survival (BCRFS) was calculated from the date of RP to the date of documented BCR or the last follow-up for patients without BCR.

Statistical analyses included univariable and multivariable Cox proportional hazards regression models to identify significant predictors of BCR. A nomogram was developed based on the multivariable model to predict BCRFS at 3 and 5 years post-RP. The nomogram’s performance was evaluated using the concordance index (c-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analyses. Internal validation was performed using a bootstrap technique with 1000 resamples.

The study found that PSA nadir and MTD were independent predictors of BCR. Patients with a detectable PSA nadir (≥0.01 ng/mL) had significantly shorter BCRFS compared to those with an undetectable PSA nadir (<0.01 ng/mL). Similarly, patients with an MTD greater than 2.9 cm had shorter BCRFS than those with an MTD of 2.9 cm or less. The combination of PSA nadir and MTD further stratified patients into risk groups, with those having both risk factors experiencing the shortest BCRFS.

The novel nomogram included PSA nadir, MTD, Gleason score, SM status, and SVI. It demonstrated a c-index of 0.76, which was slightly higher than the CAPRA-S score’s c-index of 0.70 in the study cohort. The nomogram’s calibration plots showed good agreement between predicted and observed BCRFS at 3 and 5 years. Time-dependent ROC curves and decision curve analyses confirmed the nomogram’s superior predictive performance compared to the CAPRA-S score and a basic model that excluded PSA nadir and MTD.

The study concluded that incorporating PSA nadir and MTD into a conventional predictive model significantly improves the accuracy of BCR prediction after RP. The newly developed nomogram is a valuable tool for risk stratification and follow-up planning, providing clinicians with a more precise means of identifying patients at higher risk of BCR who may benefit from closer monitoring or adjuvant therapies.

Several limitations of the study were noted. The retrospective design and relatively small sample size may limit the generalizability of the findings. Additionally, the study lacked external validation, and the follow-up duration was insufficient to analyze overall survival outcomes. Future research should address these limitations by conducting prospective studies with larger, more diverse cohorts and longer follow-up periods.

In summary, this study highlights the prognostic significance of PSA nadir and MTD in predicting BCR after RP. By integrating these variables into a comprehensive nomogram, the study provides a robust tool for improving post-operative management and outcomes for prostate cancer patients. The findings underscore the importance of considering both biochemical and imaging markers in the development of predictive models for cancer recurrence.

doi.org/10.1097/CM9.0000000000001607

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