Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading

Pichon, A.; Neuzillet, Y.; Botto, Henry; Jp, Raynaud; Radulescu, C.; Molinié, Vincent; Hervé, Jean Marie; Lebrét, Thierry

doi:10.1038/pcan.2015.44

Cited by 30 publications

(28 citation statements)

References 55 publications

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“…Pichon et al [33] had shown in a larger study population that a low serum testosterone level was an independent predictor of a predominant Gleason pattern 4 at radical prostatectomy and of upgrading from low- to high-grade PCa between needle biopsies and prostatectomy specimens. Accordingly, the San Francisco et al study [31] showed that men on AS with low serum free testosterone levels had more than four times the risk of disease reclassification, suggesting the need for further studies to assess testosterone as a tool to better select patients for AS.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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

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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Predictors from the literature include low prostate volume/weight, 3 higher PSA level,5, 22, 23 higher PSA density, 24 older age, 5 clinical stage T2, 25 time interval between diagnosis to RP,7, 23 percentage positive biopsy cores,7, 22 Cancer of the Prostate Risk Assessment (CAPRA) score, 22 higher body mass index,22, 24 and low serum testosterone 8 …”

Section: Discussionmentioning

confidence: 99%

“…Many studies have examined variables that may help to predict pathological upgrading of GS from biopsy to RP, including high prostate-specific antigen (PSA) level, 5 advanced patient age, 5 the level of pathologist expertise, 6 time from biopsy to surgery, 7 serum testosterone level, 8 treatment with brachytherapy, 9 percentage tumor involvement, 10 prostate size or volume, 1 and number of core biopsies 11 …”

Section: Introductionmentioning

confidence: 99%

Gleason group concordance between biopsy and radical prostatectomy specimens: A cohort study from Prostate Cancer Outcome Registry – Victoria

Evans

Bandarage

Kronborg

et al. 2016

Prostate International

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BackgroundA new prostate cancer (PCa) prognostic grading system [Gleason groups (GGs)] has been proposed based on the contemporary Gleason scores (GSs), which has five simplified prognostic categories. The objective of this study was to evaluate the agreement between the GGs of prostate biopsy and radical prostatectomy specimens and to identify predictive factors for upgrading GGs.MethodsA total of 5339 cases of RP notified to the Prostate Cancer Outcomes Registry, Victoria, Australia over 6 years (2009–2014) from 46 hospitals, were included. The upgrading was evaluated using the new PCa prognostic grading system, the International Society of Urologic Pathology grade groups, which has five prognostic categories. GG 1 is GS ≤ 6, GG 2 is GS 3 + 4 = 7, GG 3 is GS 4 + 3 = 7, GG 4 is GS 8, and GG 5 is GS 9 and 10. Predictors of upgrading were assessed using univariate and multivariate models.ResultsThe GG of prostate biopsies and RP specimens were concordant in 54.5% of cases, while 31.1% were upgraded and 14.3% were downgraded. Longer time interval between biopsy and RP [44–99 days: odds ratio (OR) = 1.3, 95% confidence interval (CI) = 1.1–1.6; > 99 days: OR = 3.0, 95% CI = 2.4–3.8), and RP performed in a metropolitan hospital (biopsy in a regional hospital: OR = 2.2, 95% CI = 1.6–3.2, biopsy in a metropolitan hospital: OR = 1.7, 95% CI = 1.2–2.2) were significant predictors of GG upgrading. Patients who were diagnosed by transperineal biopsy compared to transrectal ultrasound (OR = 0.6, 95% CI = 0.5–0.8) and higher percentage of positive biopsy cassettes (25–62.5%: OR = 0.7, 95% CI = 0.6–0.8, > 62.5: OR = 0.6, 95% CI = 0.5–0.8) were significantly associated with less likelihood of upgrade.ConclusionThe lack of concordance among hospitals may be attributable to the specialist expertise of the pathologist. Expert review of specimens may help to overcome this discordance. Clinicians should consider clinical parameters and potential limitations of the GG at biopsy when making treatment decisions with regard to PCa.

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“…19 Similarly, Pichon et al showed, among subjects undergoing RP for PCa, that lower testosterone levels were associated with higher-grade PCa and with increased risk of GS upgrading from prostate biopsy to specimens from surgery. 20 Park et al 9 demonstrated a correlation between hypogonadism and unfavorable outcomes in prostatic biopsies, such as increased incidence of GS ≥ 8. Several studies, despite adopting different thresholds for the definition of hypogonadism, have confirmed an association between low testosterone levels and adverse characteristics and outcomes for PCa, including higher Gleason score, 21,22 higher pathological stage 10,22 and increased risk for disease progression.…”

Section: Discussionmentioning

confidence: 99%

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer

Albuquerque

Guglielmetti

Barbosa³

et al. 2017

Rev. Assoc. Med. Bras.

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Objective: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. Method: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. Results: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). Conclusion: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

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Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading

Cited by 30 publications

References 55 publications

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

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

Gleason group concordance between biopsy and radical prostatectomy specimens: A cohort study from Prostate Cancer Outcome Registry – Victoria

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer

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