Prostate cancer staging falls short before surgery, single-center study finds

When doctors decide how to treat prostate cancer, they usually rely on a clinical stage worked up from examinations, prostate-specific antigen tests, magnetic resonance imaging and biopsy findings. A new retrospective study from Jordan suggests that this preoperative picture often misses the mark for the local extent of the tumor. In a cohort of 97 men who underwent radical prostatectomy at King Hussein Cancer Center between 2006 and 2021, clinical and pathological T staging agreed in only 61.9 percent of cases, while nodal staging agreed in 94.8 percent. The work, published in the African Journal of Urology, quantifies how often the tumor appears more or less extensive after the prostate has been removed than it did before surgery.

The research team, led by Alaa Tarazi and colleagues, set out to measure the gap between what clinicians conclude before operation and what pathologists find in the surgical specimen. They classified each patient as correctly staged, understaged or overstaged for T stage, meaning the clinical stage was equal to, lower than or higher than the pathological stage. For nodal stage, only clinical understaging was observed. Agreement was quantified with the kappa statistic: values from 0.21 to 0.40 indicate fair agreement, 0.41 to 0.60 moderate agreement, 0.61 to 0.80 substantial agreement and 0.81 to 1 almost perfect agreement.

The cohort was drawn from 118 men initially identified; 21 were excluded for missing radiological data, leaving 97 for analysis. Their mean age was 67.7 years and their mean initial prostate-specific antigen level was 20.86 nanograms per milliliter, with 55 patients at or above 10 and 42 below that threshold. The average prostate lesion measured 1.54 centimeters and the mean prostate volume was 51.95 cubic centimeters. Most lesions were scored PI-RADS 5, with 64 patients in that group, 32 at PI-RADS 4 and one at PI-RADS 3. Seventy-three men had Gleason scores below 8 on biopsy, while 24 had scores of 8 or higher.

For T stage, the distribution of clinical assignments was 62 patients at cT2, 17 at cT3a and 18 at cT3b. When the removed prostates were examined, understaging proved far more common than overstaging: 28 patients, or 28.9 percent, had tumors that proved more extensive than their clinical stage suggested, while 9 patients, or 9.3 percent, were overstaged. Men assigned cT2 fared worst, with an understaging rate of 43.5 percent. The kappa value for T-stage agreement was 0.41, with a 95 percent confidence interval of 0.27 to 0.55 and a p-value below 0.001, placing the agreement at the boundary between fair and moderate and indicating that the association was statistically significant but not strong.

Nodal staging told a different story. Eighty-six patients were classified cN0 and 11 as cN1 before surgery. Clinical assessment correctly identified 94.2 percent of the pathologically node-negative cases and all of the node-positive cases, and overall concordance reached 94.8 percent, with a kappa of 0.79 and a 95 percent confidence interval of 0.61 to 0.96. Yet the aggregate numbers concealed a diagnostic weakness. The sensitivity of clinical N staging for detecting pathological N1 disease was only 54.5 percent, with a confidence interval of 23.4 to 83.3 percent, while specificity was 94.2 percent. The positive predictive value matched the sensitivity at 54.5 percent and the negative predictive value was 94.2 percent. All five discordant cases were node-negative men whose nodal involvement was discovered only in the specimen.

To probe which factors might explain the T-stage mismatches, the authors ran an exploratory multinomial logistic regression using correctly staged patients as the reference group. Larger prostate volume emerged as the one variable associated with both directions of error. Each additional cubic centimeter of prostate volume raised the odds of understaging by a small amount, with an odds ratio of 1.04 and a confidence interval of 1.00 to 1.07, and similarly raised the odds of overstaging, with an odds ratio of 1.06 and a confidence interval of 1.00 to 1.13, both with p-values of 0.04. Initial prostate-specific antigen level, lesion size, Gleason grade group and PI-RADS score showed no statistically significant association with T-stage discrepancy. Compared with cT3b disease, cT2 stage was associated with lower odds of overstaging, with an odds ratio of 0.01, while cT3a showed a non-significant trend in the same direction.

The authors themselves urge restraint in reading these regression results. Because only nine patients were overstaged, the model was exploratory, and several confidence intervals came close to the null value of 1.00. The paper states plainly that prostate volume should not be considered an established predictor of T-stage discrepancy on the basis of these findings. For the nodal stage, the situation was even more constrained: with only five discordant cases, no multivariable predictor analysis was attempted, so the study cannot say anything reliable about which clinical or radiological factors drive nodal understaging.

Why might bigger glands confound staging? The authors offer a mechanistic account grounded in prior literature. Large prostates complicate digital rectal examination and multiparametric magnetic resonance imaging alike, since a wider field of view can reduce resolution and introduce artifacts. Benign conditions such as benign prostatic hyperplasia and prostatitis can also mimic malignant lesions on imaging, creating diagnostic confusion. Imaging may fail to capture the full extent of a tumor, particularly when lesions appear isointense on magnetic resonance imaging, a pattern common in early-stage disease. Biopsy sampling adds its own uncertainty, because cores may not represent the heterogeneous morphology of the whole tumor, and the digital rectal examination, often the first assessment, misses cancers even when it feels normal, with accuracy varying by examiner experience and technique.

The cT3b signal points in a related direction. Clinical stage T3b denotes suspected seminal vesicle invasion, a feature tied to adverse pathological and oncological outcomes. The authors note that multiparametric magnetic resonance imaging can yield false positives for seminal vesicle invasion because of anatomical variation, inflammation or post-biopsy changes, and they caution that overreliance on imaging may lead to overtreatment and unnecessarily aggressive management. On the nodal side, physical examination cannot reach regional lymph nodes at all, and microscopic metastatic deposits can escape detection on conventional imaging, which the authors suggest explains the five understaged cases despite the high overall concordance.

The study carries important caveats. Its retrospective design risks selection bias, since analysis depended on the completeness of existing records, and the exclusion of 21 men with missing radiological data narrowed the sample. The 15-year window spanned an era in which clinical staging leaned more on examination before magnetic resonance imaging became routine in the diagnostic pathway, so the modalities contributing to clinical stage were not uniform across the cohort. The authors also emphasize that the study did not evaluate prostate-specific membrane antigen PET/CT, an advanced imaging technique that has shown improved sensitivity and specificity for detecting lymph node metastases in other research; they call for prospective studies to test whether such imaging improves nodal staging concordance. For now, the message for clinicians is measured: clinical staging remains imperfect for local tumor extent, nodal understaging is rare but real, and larger, standardized cohorts are needed to confirm which patients are most at risk of a staging surprise in the surgical specimen.

Subject of Research: Agreement between clinical and pathological T and N staging in prostate cancer patients undergoing radical prostatectomy

Article Title: Clinical versus pathological staging in prostate cancer: insights from a retrospective cohort study

Article References: Tarazi, A., Ammar, O., Mubarak, N., Khzouz, J., Ghanem, R., Al-Kailani, Z., Abu-Hijlih, R., & Khairy, A.-H. (2026). Clinical versus pathological staging in prostate cancer: insights from a retrospective cohort study. African Journal of Urology, 32(1), Article 82. https://doi.org/10.1186/s12301-026-00631-0

Image Credits: AI Generated

DOI: 10.1186/s12301-026-00631-0

Keywords: prostate cancer, clinical staging, pathological staging, radical prostatectomy, kappa statistic, understaging, overstaging, prostate volume, lymph nodes, MRI, PSA, retrospective cohort