With the increase in PSA screening, most men found to have prostate cancer currently present with clinically localized disease [5
]. Numerous studies, mostly done before the widespread use of PSA testing, have shown that preoperative PSA level, Gleason score, LNI, SM status and pathological stage are independent predictors of cancer recurrence after treatment with RP [10
]. However, there has been an ongoing search for additional variables, such as tumour volume, to help predict which patients are at high risk of recurrence and might therefore benefit from adjuvant treatment [2
]. Nevertheless, the importance of tumour volume as an independent predictive variable remains controversial, especially given the recent stage migration that has occurred. In the present study of 856 patients, we found that tumour volume associated weakly with outcomes on univariate analysis, and that there was no evidence for tumour volume as a predictor of biological outcomes independent of prostate cancer stage, grade and PSA level. This conclusion also held true for patients who are considered at low risk of biochemical recurrence.
Studies in the PSA era analysing the effect of tumour volume on biochemical recurrence have yielded mixed results. In 2006, Nelson et al.
] concluded that tumour volume was an independent predictor of PSA recurrence in 431 men treated by RP from 2000 to 2001. In that study, mean tumour volume associated with pathological stage and was significantly different between patients with and without recurrence (6.8 and 2.6 mL, respectively). On multivariate analysis, tumour volume as a continuous variable predicted biochemical recurrence. The results were not presented using tumour volume as a categorical variable or stratified by grade. In the present study with a larger cohort and longer follow-up, there was a greater risk of biochemical recurrence on univariate analysis for tumour volumes of > 4 mL. However, after adjusting for stage or grade, tumour volume was not significantly associated with progression as either a continuous or categorized variable.
Similarly, studies by Solomon et al.
] and Kikuchi et al.
] assessing the significance of tumour volume in clinically localized prostate cancer found that it added no independent prognostic information on multivariate analysis. Both studies had comparable mean and median tumour volumes to the present cohort, although the follow-up time was somewhat less. As in the present study, both groups showed that tumour volume (low or high) was not a predictor of PSA recurrence in a subset of low-risk patients.
Recent findings by Merrill et al.
] in a large population undergoing RP for localized prostate cancer again confirmed this observation, finding that regardless of tumour volume, low-risk patients had a low rate of cancer progression. Notably, they found that tumour volume was a significant independent predictor of recurrence in patients with Gleason scores of ≥□7, although the sample size for this subgroup was small. Cheng et al.
] reported that the maximum tumour diameter predicted biochemical recurrence and correlated with tumour volume in 364 patients, although the follow-up in that study was short (1.5 months to 2 years). By contrast, Van Oort et al.
] reported no significant relationship between tumour volume and maximum tumour diameter with biochemical recurrence in high-risk localized prostate cancer, which is also consistent with our data.
A tumour volume of < 0.5 mL is often cited as a criterion, along with low Gleason score and stage, for defining insignificant prostate cancers [17
]. In the present analysis we found no suggestion that tumours of < 0.5 mL but otherwise low-risk features (organ-confined, negative SMs, Gleason = 3 + 3) had any higher risk of recurrence than smaller tumours. Conversely, small tumours with higher grade or stage can show aggressive behaviour despite being small [13
]. Based on our findings, tumour volume has limited value in predicting the clinical behaviour of localized prostate cancer, whether in the overall cohort or among those with otherwise low-risk features.
We recognize certain limitations of this study, most importantly that it was retrospective, and that tumour volume measurements were not available for all patients in the database. More than one pathologist reviewed the prostate specimens, which might have affected the reporting of tumour volume by visual estimation. In addition, the follow-up was limited in some men who have not recurred, particularly those diagnosed in the earlier years of the cohort. Lastly, all men in the current study had a RP and therefore were pre-selected based on certain risk features. Tumour volume could be a significant predictor in those men with more advanced disease, as reported previously, who were not well represented in this cohort [18
In conclusion, in a contemporary cohort of men treated with RP for clinically localized disease, the risk of biochemical recurrence did not increase consistently with increasing tumour volume. There is no evidence that tumour volume predicts biological outcomes, independent of stage, Gleason grade and PSA level. Tumour volume should not be considered an independent marker of disease risk or prognosis in men with localized disease.