In this study, we investigated the overall contribution of TV according to the risk group systems from D’Amico criteria and NCCN guidelines and observed that TV significantly increased in the higher risk groups of both systems. The patients of the low risk group exhibited a TV of 2–3 cm3, with a tumor diameter between 1.4 and 1.6 cm when the tumor is assumed to be spherical, and a TV between 1.3 and 1.4 cm when the tumor is assumed to be a regular hexahedron. Large tumors were significantly related to an increased postoperative BCR in our multi-variate Cox proportional hazard analyses with both categorical and continuous variables. The preoperative PSA, clinical stage, prostate volume, percentage of positive biopsy cores, and maximal tumor length among positive biopsy cores were significantly related to high TV in our multi-variate regression tests.
TV has been presented as a significant prognostic factor of PCa in several papers 2, 4, 5–12. Stamey et al. reported that cancer volume and high Gleason score were significantly related with worse BCR-free survival after analyzing the results of 379 patients who were treated with radical prostatectomy2. They argued that the exact way to predict cancer volume may be helpful in predicting the outcomes of PCa surgery. Subsequently, Nelson et al investigated the effect of TV on pathologic outcomes and biochemical recurrence after surgery5. They concluded that TV directly correlated with pathological stage and PSA recurrence after radical prostatectomy; therefore, TV was revealed as an independent predictor for worse prognosis in patients with localized PCa. Another study by Chun et al. showed that cancer volume and high Gleason score were the independent predictors for postoperative BCR in their relatively large cohort of 780 participants treated with radical prostatectomy4. However, there were other studies showing contradictory results regarding the use of TV as a predictive prognostic factor13–16. Kikuchi et al. also analyzed a larger cohort of 1,302 participants who were also treated with radical prostatectomy. They observed only a weak relationship with postoperative prognosis, but no statistically significant results were obtained from multi-variate analyses13. Another study by May et al. reported that absolute TV was unable to predict postoperative BCR, unlike relative TV (TV/total prostate volume), which showed significant results in predicting prognosis14. Subsequently, Merrill et al analyzed a large cohort of 1,833 participants who were also treated with radical prostatectomy and found that TV was significantly associated with a higher rate of BCR in the high pathologic Gleason score subgroup (≥ 3 + 4), but not in the Gleason 6 subgroup (3 + 3)15. Furthermore, another study by Uhlman et al. analyzed data from a large cohort of 3,528 participants who were treated with radical prostatectomy to evaluate the prognostic influence of TV16. They analyzed TV both by categorical and continuous variables and concluded that TV did not show any significant association with BCR-free survival, even though significant difference existed in their BCR-free survival rates after univariate Kaplan-Meier analyses. However, we believe that their study may have some limitations. First, they included patients who were treated from 1988 to 2008 without any pathologic re-review on the Gleason grading. As there was a major update on Gleason grading in 2006 by the International Society of Urologic Pathology (ISUP), there is a possibility of confounding influence from the heterogenous definition for Gleason scoring depending on the time period. Second, our cohort has a more aggressive disease, in terms of pathologic Gleason grade and PSA level, than those in previous studies. As like the aforementioned study by Merrill et al, which showed that TV was associated with postoperative prognosis only in patients with high Gleason scores (≥ 4 + 3), the more aggressive disease profiles of our study may have caused the contrasting results compared with Uhlman et al. Third, we observed a relatively high rate of positive surgical margins from Uhlman et al’s study, which may also be connected to confounding effect in their study.
Lately, focal therapy is gaining more attention with clinical benefits in terms of better erectile and urinary functions after treatment20. However, there are still limitations for focal therapy, because tumor location cannot be exactly predicted using conventional imaging modalities and biopsy protocols21. The understanding of the epidemiology of TV is quite important when planning and finding optimal candidates for focal therapy. We observed from our results that the mean TV was about 2.0 cc for very low risk, 3.1 cc for low risk, and 3.2 cc for favorable intermediate risk group. Patients in the unfavorable intermediate risk group showed significantly larger TV than those in the favorable intermediate risk group (3.2 ± 3.7 cc versus 5.2 ± 4.8 cc, P < 0.001). From our volumetric results of TV, we believe that the optimal candidates for focal therapy could be patients between very low risk and favorable intermediate risk groups. However, the patients in the very low risk group should be recommended for active surveillance.
Our study is certainly not without limitations. First, it is limited by its retrospective analyses, even though the data on TV was prospectively accumulated. Second, there is a possibility of selection bias since we only included patients treated with radical prostatectomy. Third, the present study only analyzed the total TV but not the detailed pathologic information about number of tumors and location, which is also important for prognosis of PCa patients. Even so, we believe that we provided the most recent data regarding the actual epidemiology of TV in patients treated with radical prostatectomy, which makes our study clinically meaningful.