Is the density of prostate tissue truly 1 gram per milliliter?—an evaluation of HoLEP specimens

Introduction

Accurate measurement of preoperative prostate size is important for surgical decision-making for patients with benign prostatic hyperplasia (BPH). Prostate volume (PV) is used instead of prostate weight (PW) to estimate prostate size, under the assumption that prostate tissue density approximates that of water (1 g/mL). PV is commonly calculated on cross-sectional imaging using the ellipsoid formula (three dimensions multiplied by π/6), or via more sophisticated segmentation algorithms (1,2).

Current American Urological Association guidelines support interchanging weight (in grams) and volume (mL), citing prostate density (PD) as ~1.05 g/mL (3). However, this is based on surprisingly little experimental in vitro evidence. A study utilizing volume displacement determined PD among 57 radical prostatectomy specimen fragments to be 0.98 g/mL (4). Another study examined 20 radical prostatectomy specimens and found the PD to be 1.02 g/mL (5). Guidelines are therefore based on whole-gland prostate tissue, not transitional zone tissue—which may have a different density and is clinically relevant due to this being the primary tissue removed during BPH procedures.

Holmium laser enucleation of the prostate (HoLEP) is a size-independent option for BPH treatment (6). HoLEP removes the obstructing transition zone adenomatous tissue first with enucleation, i.e., carving out the tissue, followed by morcellation, whereby the adenoma is debulked in fragments and evacuated through the endoscope. HoLEP specimens provide a unique opportunity to investigate the volume-to-weight relationship in a largely non-cancerous prostate (7,8).

HoLEP success may be assumed to correlate with enucleation efficiency, i.e., how much adenomatous tissue is removed compared to preoperative PV. However, the amount of prostate tissue removed during HoLEP has not been shown to predict same-day trial of void success (9). A high enucleation ratio (enucleation weight divided by transition zone volume) can hinder early recovery of stress urinary incontinence (SUI) after HoLEP (10). This contrasts with transurethral resection of the prostate, in which the volume resected has been shown to positively correlate with improved postoperative voiding function (11). Such discrepancies in outcomes may occur if PV and PW are not in fact interchangeable across all prostate sizes.

Prostate size may influence PD, as larger prostates may have different proportions of stromal and glandular tissue (3,12). To our knowledge, the volume-to-weight relationship in the transition zone of non-cancerous prostates or very large prostates has not been studied. The objective of this study was to directly measure transitional zone PD and identify clinical and pathological factors that may influence density. We present this article in accordance with the MDAR reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0454/rc).

Methods

An experimental, in vitro study of HoLEP specimens was conducted intraoperatively at Northwestern University between June and August 2024. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Northwestern University (No. STU00214996) on May 18, 2021. Informed consent was obtained from all HoLEP patients. A total of 50 patients were included. Specimens were collected intraoperatively from consecutively sampled HoLEP patients. There were no exclusion criteria. Demographic and clinical variables included age, preoperative prostate size on imaging, history of prior BPH surgery, urinary tract infection (UTI) history, finasteride use, and prostate cancer history. Preoperative PV was defined in mL utilizing the ellipsoid formula. Density was defined as mass/volume (g/mL). Volume was defined in mL. Weight was measured directly in grams (g).

All HoLEP procedures were performed by a single surgeon (A.E.K.). Following enucleation, the prostate tissue was morcellated and collected. A graduated cylinder prefilled with 200 mL of sterile saline was placed on a calibrated digital scale, and its weight was recorded (Figure 1). PV (in mL) was measured by fluid displacement: the morcellated tissue was fully submerged in the cylinder, and PV was recorded as the volume of saline displaced above the 200 mL baseline. The displaced volume was read from the cylinder’s graduation marks and confirmed with a scaled ruler. PW (in g) was recorded simultaneously as the increase in scale weight after the tissue was added, i.e., the weight of the cylinder with tissue minus the weight of the prefilled cylinder alone. PD was calculated as PW divided by PV (g/mL). Intraoperative metrics, including enucleation and morcellation time, were also recorded. All specimens were submitted to the pathology department following standard protocol. Pathologists recorded the pathology weight and dry weight. Dry density was calculated as the ratio of dry weight to PV.

Figure 1 Intraoperative measurement technique of morcellated transition zone prostate weight, volume, and density. Created with the assistance of OpenAI, ChatGPT.

Statistical analysis

Continuous variables were summarized as medians with interquartile ranges (IQR) and 95% confidence intervals (CI). Comparisons of PD between subgroups (finasteride use, prior BPH surgery, UTI history, prostate cancer history, and prostate size ≥100 g) were performed using the Wilcoxon rank-sum test. Spearman correlations were used. A P value of <0.05 was considered statistically significant.

Results

A total of 50 consecutive patients were enrolled in the study, of whom 48 had complete volume and weight data and were included in the final analysis (Table 1). Of these, six had a history of prostate cancer prior to HoLEP, 12 had undergone a prior surgical intervention for BPH, and 19 patients had a history of UTI. A total of 26 patients had prostates ≥100 mL on preoperative imaging.

The median preoperative PV on imaging calculated via the ellipsoid formula was 112.0 mL (IQR: 80–150). A total of 32 patients (65.4%) had preoperative imaging via computed tomography (CT) or magnetic resonance imaging (MRI). The rest had a combination of transrectal ultrasound (TRUS) or cystoscopy, and the modality was not explicitly reported in the chart for three patients (e.g., a note from an outside hospital chart without an accompanying imaging modality). The median PW reported by pathology was 69.33 g (43.51–99.4). Pathology PW was significantly less than intraoperative PW (P=0.03). The median enucleation efficiency was 2.31 g/min (1.6–2.9).

Fresh intraoperative PW was strongly correlated with pathology-reported weight (Spearman’s ρ=0.97, n=48), with a median difference of 2.5% between the two measurements.

Finasteride use, prior BPH surgery, UTI history, and prostate cancer history were not associated with mean differences in PD (Table 2).

On scatterplot analysis, most prostate densities clustered around 1 g/mL (Figure 2). Twenty-four (49.0%) had density <0.95 g/mL, 17 (34.7%) had a density between 0.95 and 1.05 g/mL, and seven (14.3%) had density >1.05 g/mL. Median tissue density was 0.95 g/mL (IQR 0.90–1.01), which was statistically significantly lower than the theoretical 1.0 g/mL assumption (Wilcoxon signed-rank test, P=0.001).

Figure 2 Resected PW (g) plotted against PV (mL). The dashed line marks density = 1 g/mL, where weight equals volume. Points below the line (density <1) indicate that volume overestimated the resected weight. Density category defined as <0.95, 0.95 to 1.05 (≈1), and >1.05 g/mL. PV, prostate volume; PW, prostate weight.

Median resected PV [74.25 mL (IQR 49.4–106.3)] was significantly greater than median resected PW [71 g (IQR 41.0–108.0)], with a median paired difference (PV − PW) of 3.35 mL (95% CI 1.10–5.35, Wilcoxon signed-rank test, P=0.005). Consistent with this, measured resected PV exceeded measured PW by a median overestimation of 5.2% (IQR: −1.4% to 11.6%). PV exceeded resected weight in 33 (69%), indicating a density below 1 g/mL (Figure 3). The distribution was right-skewed, with a small number of specimens showing overestimation exceeding 50%.

Figure 3 Distribution of percent PV overestimation relative to resected PW. Values >0 indicate overestimation and values <0 indicate under-estimation. Positive values indicate that volume exceeded weight, corresponding to a density below 1 g/mL. Negative values indicate that weight exceeded volume, corresponding to a density above 1 g/mL. The dashed line marks exact agreement at zero percent, and the solid line marks the median. PV, prostate volume; PW, prostate weight.

Patients with prostates ≥100 mL demonstrated a higher PD compared to those with smaller prostates [0.98 (95% CI: 0.95–1.03) vs. 0.92 (95% CI: 0.81–0.97), P=0.004]. When stratified by size, smaller prostates (<100 mL) had a median percent overestimation of PW of 7.1% (IQR 1.4–17.1) versus −0.05% (IQR −2.6 to 5.1) in larger prostates, respectively (P=0.03).

Higher PD was significantly associated with longer morcellation time (ρ=0.50, P<0.001), increased laser energy utilization (ρ=0.57, P<0.001), and longer enucleation time (ρ=0.40, P=0.005).

Discussion

In this study, the directly measured transitional zone PD was 0.95 g/mL, which although statistically significantly different from 1 g/mL, clinically supports the practice of assuming PD approximates the density of water. When stratified by resected volume, the deviation from the 1:1 assumption was more pronounced among smaller specimens. Specimens <100 mL had a median PV-to-PW overestimation of 7.1%, whereas specimens ≥100 mL showed essentially no deviation from the density of water. The modest overall overestimation was likely driven by the more numerous smaller prostates, while larger specimens more closely approximated the expected 1 mL:1 g relationship. Finasteride use, prior BPH surgery, UTI history, and prostate cancer history were not associated with differences in PD.

Our results indicate that transitional zone tissue may be slightly less dense than water, although overall the 1:1 assumption of interchanging PV with PW is reasonable.

There is relatively sparse literature providing experimental evidence to support the presumed 1:1 relationship between PV and PW. The current evidence is largely based on smaller prostates in which cancerous tissue was present. For example, in the aforementioned histopathologic study of 20 radical prostatectomy specimens, the median prostate size was 39.5 mL (standard deviation 27.3 mL) and the study included only one prostate larger than 80 g (5). The 2005 study on 57 radical prostatectomy specimens included only fragments, rather than whole specimens (4). Although both support a 1:1 relationship between PV and PW, it is uncertain if this relationship holds in larger prostates with noncancerous tissue.

To our knowledge, the present study is the first to assess true PV and weight in HoLEP specimens from patients. This is important because, compared to prior cohorts which utilized radical prostatectomy specimens, the current cohort largely consisted of patients who did not have a history of prostate cancer.

Across the observed range of PV, smaller prostates demonstrated a greater tendency toward positive percent differences between measured volume and weight, indicating that volume more frequently exceeded weight in smaller glands. In contrast, larger prostates demonstrated values closer to zero, suggesting a closer approximation to the commonly assumed 1:1 volume-to-weight relationship.

When stratified by a clinically relevant threshold of 100 mL, smaller prostates (<100 mL) demonstrated significantly greater percent overestimation compared with larger prostates (≥100 mL) (7.1% vs. −0.05%, P=0.03). The right-skew reflects a small subset of specimens with disproportionately high overestimation. These corresponded to the smallest glands, in which a modest absolute difference between weight and volume produces a large proportional difference. These findings suggest that the modest overall deviation from the 1:1 assumption observed in the cohort was primarily driven by smaller glands, whereas larger prostates more closely approximated equal volume and weight measurements.

Our findings that larger prostates tend to be denser support the practice of size-specific adjustments to improve measurement accuracy. MRI PV measured using semiautomatic segmentation analysis has been shown to correlate better with prostatectomy volume in smaller prostates (<55 mL) (1). Different formulas have also been used for smaller prostates than for larger prostates (13). This may reflect histologic differences in glandular and stromal composition, as prior studies have demonstrated that tissue distribution and capsule thickness vary with prostate size and pathology (14). Holder et al. reported pathological changes in epithelial and stromal content across prostate zones, supporting the possibility that larger prostates may develop structural changes contributing to increased density (15).

Limitations of our study include its relatively small sample size, single-center design, and possible measurement errors. As these were HoLEP specimens, and enucleated tissue is morcellated in the bladder, admixture of clot material with morcellated tissue could increase measured specimen mass in some cases. Therefore, additional components such as blood clots in larger prostates (a common finding) could have contributed to higher density. It is also possible that measurement sensitivity of the scale could make changes in smaller-volume prostates harder to read compared to changes in larger-volume prostates. Variability in imaging technique and tissue handling could have affected measurement accuracy for volume and weight (16).

Conclusions

Transitional zone prostate tissue density appears to be largely consistent with water density, thus supporting the 1:1 conversion of PW in grams to PV in mL, even in prostates that predominantly do not harbor prostate cancer.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the MDAR reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0454/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0454/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0454/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0454/coif). A.P. reports consulting fees from Karl Storz and serves as an instructor for an event held by Karl Storz. A.E.K. reports consulting fees from Richard Wolf, Karl Storz, and Boston Scientific, and serves as a member of the Data Safety Monitoring Board of Uriprene. P.X. reports consulting fees from Wolf. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Northwestern University (No. STU00214996) on May 18, 2021. Informed consent was obtained from all HoLEP patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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