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Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance

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ABSTRACT

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed.

In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy.

Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSA<10ng/ml, two or fewer cancer cores, Gleason score (GS)=6 and PSA density<0.2 ng/mL/cc. Reclassification was defined as upstaging (stage>pT2) and upgrading (GS=7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery.

Low serum testosterone levels (<300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease.

In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor when a close AS program is considered as treatment option

No MeSH data available.


ROC Curve analysis for testosterone as a predictor of predominant Gleason score 4
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Figure 4: ROC Curve analysis for testosterone as a predictor of predominant Gleason score 4

Mentions: Total testosterone levels showed a significant association with all the main outcomes of interest (Table 2). In particular, when treated as a continuous variable, lower total testosterone levels (median [IQR]) were associated with reclassification in terms of upstaging (299.5 [250 ; 390] vs. 488.5 [401 ; 600]; p < 0.001), upgrading (400.5 [292.25 ; 534] vs. 497.5 [401 ; 600]; p < 0.001), unfavorable disease (290 [250 ; 300] vs. 456 [390 ; 567]; p < 0.001) and predominant Gleason score 4 (300 [254 ; 502] vs. 477 [398 ; 597]; p < 0.001) . These associations were confirmed when subjects were analysed according to the presence or absence of a hypogonadism condition (total testosterone < 300 ng/dL). In addition, we found a significantly higher rate of hypogonadism in PCa patients with positive surgical margins (27.8% vs. 14.2%; p = 0.035). Of note, cancer involvement in positive cores (CIPC) was also significantly associated with all the outcomes (Table 2a and 2b). Receiver Operating Characteristic (ROC) curve analysis supported the prognostic role of total testosterone in the reclassification of men on AS (Figures 1-4). The corresponding area under the curve (AUC) ranged from 0.66 (95% C.I. 0.60 to 0.72) for upgrading, to 0.81 (95% C.I. 0.75 to 0.88) for upstaging. Sensitivities and specificities of total testosterone for each of the outcomes and according to both the “best combination” cut-off point and the cut-off point denoting a condition of hypogonadism are reported in Table 3a and 3b. To assess the role of total testosterone as an independent predictor of reclassification, a set of multivariable logistic regression models including age, PSA, PSA density, digital rectal examination (DRE) status and cancer involvement in positive cores (CIPC) was constructed (Table 4). Total testosterone included in these base models was a significant independent predictor, both as a continuous and dichotomous variable, of upstaging, upgrading and unfavorable disease. However, a significant gain in predictive accuracy was only detected for the outcome of upstaging (15.2% when considering total testosterone as a continuous variable and 12.4% when treating total testosterone as a dichotomous variable) and predominant Gleason score 4 (9.4% or 8.3%, respectively). No advantages over the base model were observed for the outcome of upgrading, unfavourable disease and for the prediction of positive surgical margins.


Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance
ROC Curve analysis for testosterone as a predictor of predominant Gleason score 4
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392340&req=5

Figure 4: ROC Curve analysis for testosterone as a predictor of predominant Gleason score 4
Mentions: Total testosterone levels showed a significant association with all the main outcomes of interest (Table 2). In particular, when treated as a continuous variable, lower total testosterone levels (median [IQR]) were associated with reclassification in terms of upstaging (299.5 [250 ; 390] vs. 488.5 [401 ; 600]; p < 0.001), upgrading (400.5 [292.25 ; 534] vs. 497.5 [401 ; 600]; p < 0.001), unfavorable disease (290 [250 ; 300] vs. 456 [390 ; 567]; p < 0.001) and predominant Gleason score 4 (300 [254 ; 502] vs. 477 [398 ; 597]; p < 0.001) . These associations were confirmed when subjects were analysed according to the presence or absence of a hypogonadism condition (total testosterone < 300 ng/dL). In addition, we found a significantly higher rate of hypogonadism in PCa patients with positive surgical margins (27.8% vs. 14.2%; p = 0.035). Of note, cancer involvement in positive cores (CIPC) was also significantly associated with all the outcomes (Table 2a and 2b). Receiver Operating Characteristic (ROC) curve analysis supported the prognostic role of total testosterone in the reclassification of men on AS (Figures 1-4). The corresponding area under the curve (AUC) ranged from 0.66 (95% C.I. 0.60 to 0.72) for upgrading, to 0.81 (95% C.I. 0.75 to 0.88) for upstaging. Sensitivities and specificities of total testosterone for each of the outcomes and according to both the “best combination” cut-off point and the cut-off point denoting a condition of hypogonadism are reported in Table 3a and 3b. To assess the role of total testosterone as an independent predictor of reclassification, a set of multivariable logistic regression models including age, PSA, PSA density, digital rectal examination (DRE) status and cancer involvement in positive cores (CIPC) was constructed (Table 4). Total testosterone included in these base models was a significant independent predictor, both as a continuous and dichotomous variable, of upstaging, upgrading and unfavorable disease. However, a significant gain in predictive accuracy was only detected for the outcome of upstaging (15.2% when considering total testosterone as a continuous variable and 12.4% when treating total testosterone as a dichotomous variable) and predominant Gleason score 4 (9.4% or 8.3%, respectively). No advantages over the base model were observed for the outcome of upgrading, unfavourable disease and for the prediction of positive surgical margins.

View Article: PubMed Central - PubMed

ABSTRACT

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed.

In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy.

Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSA&lt;10ng/ml, two or fewer cancer cores, Gleason score (GS)=6 and PSA density&lt;0.2 ng/mL/cc. Reclassification was defined as upstaging (stage&gt;pT2) and upgrading (GS=7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage&gt;pT2 and predominant Gleason score 4. Total testosterone was measured before surgery.

Low serum testosterone levels (&lt;300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease.

In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor when a close AS program is considered as treatment option

No MeSH data available.