I do not follow them. One aspect of PrCa is that OS is hardly, if at all, affected by current treatments.
[OT: RVNC. 25-50% return in 2 years.]
MESO-Rx
Anabolic Steroids
Prostate ...
- Thread starter Michael Scally MD
- Start date
I do not follow them. One aspect of PrCa is that OS is hardly, if at all, affected by current treatments.
[OT: RVNC. 25-50% return in 2 years.]
Putting them on my watch list, & like the action, but not a lot of vol.. Here's one for you ACRX, the first subliminal FDA approved opioid. DOD contract, and going live in January. End of Q1, 1. BO or 2. Sales numbers which at 11-Dec was not discussed. It's extremely cheap right now, but 1st of the year will be reversing once the street gets back.
Metabolic Consequences of Gonadotropin-Releasing Hormone Agonists Vs Orchiectomy
Objectives To compare the metabolic changes between men with advanced prostate cancer commenced on a gonadotropin-releasing hormone (GnRH) agonist and those treated with orchiectomy.
Patients and Methods Fifty-eight hormone-naive men with advanced prostate cancer were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg/24 week depot injections. The participants were followed for 48 weeks, with study visits at baseline, 12, 24 and 48 weeks.
The primary endpoint was changes in fasting plasma glucose. Secondary endpoints included changes in body composition (i.e. weight, fat mass, visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], lean body mass [LBM] and android/gynoid fat [AG] ratio) assessed with dual X-ray absorptiometry, serum lipid profiles, and insulin resistance evaluated during an oral glucose tolerance test. Linear mixed models were used to analyse the between-group differences.
Results No treatment differences in the changes in fasting plasma glucose (0.2 mmol/L, 95% confidence interval [CI] ?0.1, 0.4; P = 0.32) were observed. The orchiectomy group experienced greater increases in total fat mass (+2.06 kg, 95% CI 0.55, 3.56), SAT (+133 cm3, 95% CI 22, 243) and weight (+3.30 kg, 95% CI 0.74, 5.87) at 48 weeks than did the triptorelin group (all P < 0.05), with the increases in fat mass being moderately correlated with increases in insulin resistance (P < 0.001). No differences in changed VAT, LBM or AG ratio were observed between the groups.
The pooled analyses, combining data from both groups, showed androgen deprivation therapy (ADT) to significantly increase fat mass, SAT, VAT, serum cholesterols (total, high-density lipoprotein and low-density lipoprotein) and all measures of insulin resistance over time, while LBM decreased as compared with baseline values (all P < 0.05). These changes were apparent after only 12-24 weeks of ADT.
Conclusions Androgen deprivation therapy leads to adverse changes in body composition and increased insulin resistance and serum cholesterols, with changes already observed after only 12-24 weeks of treatment. This study further demonstrates that orchiectomy causes greater increases in fat accumulation compared with GnRH agonists and that these increases are associated with an increase in insulin resistance.
Østergren PB, Kistorp C, Fode M, Bennedbæk FN, Faber J, Sønksen J. Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study. BJU international 2018. https://doi.org/10.1111/bju.14609
Objectives To compare the metabolic changes between men with advanced prostate cancer commenced on a gonadotropin-releasing hormone (GnRH) agonist and those treated with orchiectomy.
Patients and Methods Fifty-eight hormone-naive men with advanced prostate cancer were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg/24 week depot injections. The participants were followed for 48 weeks, with study visits at baseline, 12, 24 and 48 weeks.
The primary endpoint was changes in fasting plasma glucose. Secondary endpoints included changes in body composition (i.e. weight, fat mass, visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], lean body mass [LBM] and android/gynoid fat [AG] ratio) assessed with dual X-ray absorptiometry, serum lipid profiles, and insulin resistance evaluated during an oral glucose tolerance test. Linear mixed models were used to analyse the between-group differences.
Results No treatment differences in the changes in fasting plasma glucose (0.2 mmol/L, 95% confidence interval [CI] ?0.1, 0.4; P = 0.32) were observed. The orchiectomy group experienced greater increases in total fat mass (+2.06 kg, 95% CI 0.55, 3.56), SAT (+133 cm3, 95% CI 22, 243) and weight (+3.30 kg, 95% CI 0.74, 5.87) at 48 weeks than did the triptorelin group (all P < 0.05), with the increases in fat mass being moderately correlated with increases in insulin resistance (P < 0.001). No differences in changed VAT, LBM or AG ratio were observed between the groups.
The pooled analyses, combining data from both groups, showed androgen deprivation therapy (ADT) to significantly increase fat mass, SAT, VAT, serum cholesterols (total, high-density lipoprotein and low-density lipoprotein) and all measures of insulin resistance over time, while LBM decreased as compared with baseline values (all P < 0.05). These changes were apparent after only 12-24 weeks of ADT.
Conclusions Androgen deprivation therapy leads to adverse changes in body composition and increased insulin resistance and serum cholesterols, with changes already observed after only 12-24 weeks of treatment. This study further demonstrates that orchiectomy causes greater increases in fat accumulation compared with GnRH agonists and that these increases are associated with an increase in insulin resistance.
Østergren PB, Kistorp C, Fode M, Bennedbæk FN, Faber J, Sønksen J. Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study. BJU international 2018. https://doi.org/10.1111/bju.14609
Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing Androgen Deprivation Therapy [Re: ASIH]
Context - Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT demonstrate that levator ani is exquisitely androgen sensitive.
Objective - To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved, and ADT is associated with a selective loss in leg muscle volumes.
Design - Prospective longitudinal case-control study.
Setting - Tertiary referral hospital.
Participants - 34 men newly commencing ADT and 29 age-matched PCa controls.
Main Outcome Measures - Muscle volumes (litres) of levator ani, and of primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf)
Results - Compared to controls over 12 months, men receiving ADT had a mean reduction in total testosterone from 14.1 to 0.4nmol/L and demonstrated greater decreases in levator ani (MAD -0.005litres [-0.007, -0.002], p=0.002, -16% of initial median value), gluteus maximus (MAD -0.032litres [-0.063, -0.002], p=0.017, -5%), iliopsoas (MAD -0.005litres [-0.001, 0.000], p=0.013, -5%) and quadriceps (MAD -0.050litres [-0.088, -0.012], p = 0.031, -3%). No significant differences were observed in gluteus medius and calf muscles.
Conclusion - Androgen responsiveness of levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor improves clinical outcomes.
Cheung AS, Cunningham C, Ko D-KD, et al. Selective loss of levator ani and leg muscle volumes in men undergoing androgen deprivation therapy. The Journal of Clinical Endocrinology & Metabolism 2018. Selective loss of levator ani and leg muscle volumes in men undergoing androgen deprivation therapy
Context - Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT demonstrate that levator ani is exquisitely androgen sensitive.
Objective - To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved, and ADT is associated with a selective loss in leg muscle volumes.
Design - Prospective longitudinal case-control study.
Setting - Tertiary referral hospital.
Participants - 34 men newly commencing ADT and 29 age-matched PCa controls.
Main Outcome Measures - Muscle volumes (litres) of levator ani, and of primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf)
Results - Compared to controls over 12 months, men receiving ADT had a mean reduction in total testosterone from 14.1 to 0.4nmol/L and demonstrated greater decreases in levator ani (MAD -0.005litres [-0.007, -0.002], p=0.002, -16% of initial median value), gluteus maximus (MAD -0.032litres [-0.063, -0.002], p=0.017, -5%), iliopsoas (MAD -0.005litres [-0.001, 0.000], p=0.013, -5%) and quadriceps (MAD -0.050litres [-0.088, -0.012], p = 0.031, -3%). No significant differences were observed in gluteus medius and calf muscles.
Conclusion - Androgen responsiveness of levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor improves clinical outcomes.
Cheung AS, Cunningham C, Ko D-KD, et al. Selective loss of levator ani and leg muscle volumes in men undergoing androgen deprivation therapy. The Journal of Clinical Endocrinology & Metabolism 2018. Selective loss of levator ani and leg muscle volumes in men undergoing androgen deprivation therapy
Testosterone, Testosterone Therapy and Prostate Cancer
With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer.
This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed.
Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer.
In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.
Yassin A, AlRumaihi K, Alzubaidi R, Alkadhi S, Al Ansari A. Testosterone, testosterone therapy and prostate cancer. The aging male: the official journal of the International Society for the Study of the Aging Male 2019:1-9. https://www.tandfonline.com/doi/full/10.1080/13685538.2018.1524456
With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer.
This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed.
Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer.
In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.
Yassin A, AlRumaihi K, Alzubaidi R, Alkadhi S, Al Ansari A. Testosterone, testosterone therapy and prostate cancer. The aging male: the official journal of the International Society for the Study of the Aging Male 2019:1-9. https://www.tandfonline.com/doi/full/10.1080/13685538.2018.1524456
Androgen Deprivation Therapy for Prostate Cancer and Risk of Dementia
OBJECTIVES: To study if androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia.
METHODS: Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in Prostate Cancer data Base Sweden (PCBaSe) was compared with that of prostate cancer-free men, matched on birth year and county of residency.
We used Cox's regression to calculate hazard ratios for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens as well as for men managed with watchful waiting.
RESULTS: 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median time of four years, and in both groups 6% of the men were diagnosed with dementia. Use of Gonadotropin-releasing hormone agonists (GnRH agonists, Hazard Ratio (HR): 1.15 (95%CI: 1.07-1.23) and orchiectomy, HR 1.60 (95%CI: 1.32-1.93) were associated with an increased risk of dementia, as compared to prostate cancer-free men. However, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year one to four after start of ADT. No increase in for any type of dementia was observed for men treated with antiandrogens or for men on WW.
CONCLUSION: This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT. However, there was a small increase in risk of non-Alzheimer's dementia. This article is protected by copyright. All rights reserved.
Robinson D, Garmo H, Van Hemelrijck M, et al. Androgen deprivation therapy for prostate cancer and risk of dementia. BJU international 2019. https://onlinelibrary.wiley.com/doi/abs/10.1111/bju.14666
OBJECTIVES: To study if androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia.
METHODS: Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in Prostate Cancer data Base Sweden (PCBaSe) was compared with that of prostate cancer-free men, matched on birth year and county of residency.
We used Cox's regression to calculate hazard ratios for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens as well as for men managed with watchful waiting.
RESULTS: 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median time of four years, and in both groups 6% of the men were diagnosed with dementia. Use of Gonadotropin-releasing hormone agonists (GnRH agonists, Hazard Ratio (HR): 1.15 (95%CI: 1.07-1.23) and orchiectomy, HR 1.60 (95%CI: 1.32-1.93) were associated with an increased risk of dementia, as compared to prostate cancer-free men. However, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year one to four after start of ADT. No increase in for any type of dementia was observed for men treated with antiandrogens or for men on WW.
CONCLUSION: This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT. However, there was a small increase in risk of non-Alzheimer's dementia. This article is protected by copyright. All rights reserved.
Robinson D, Garmo H, Van Hemelrijck M, et al. Androgen deprivation therapy for prostate cancer and risk of dementia. BJU international 2019. https://onlinelibrary.wiley.com/doi/abs/10.1111/bju.14666
Capogrosso P, Vertosick EA, Benfante NE, et al. Are We Improving Erectile Function Recovery After Radical Prostatectomy? Analysis of Patients Treated over the Last Decade. European Urology 2019;75:221-8. Redirecting
Background - The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery.
Objective - We examined whether these practice changes have led to observed improvements in EF rates over time.
Design, setting, and participants - We identified 2364 patients treated with either open or minimally-invasive RP at a single academic center in 2008–2015. To mitigate confounding by the surgical learning curve, only patients treated by surgeons who performed at least 100 procedures were considered.
Intervention - EF before and after RP was assessed by the International Index of Erectile Function 6 (IIEF-6), with recovery defined as IIEF-6 ≥24.
Outcome measurements and statistical analysis - We analyzed EF recovery rates of patients treated with bilateral nerve-sparing surgery and free from adjuvant/salvage treatment at the time of EF assessment. Local polynomial regression analyses explored changes in the outcomes over time. Linear and logistic regression analyses were used to estimate the influence of year of surgery on baseline variables and EF recovery.
Results and limitations - We observed a significant decrease over time of the EF recovery rates at both 12 and 24 mo post-RP (all p = 0.01). However, patient's age at surgery increased over time (mean increase of 0.5 per year; p < 0.01), with a resultant increase in risk of comorbidity (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.02–1.15; p = 0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year; p = 0.0003).
After accounting for baseline and pathological characteristics, urinary function, and type of surgery in a multivariable analysis, year of surgery was not associated with EF recovery (12 mo: OR = 0.97, 95% CI: 0.91–1.03, p = 0.4; 24 mo: OR = 0.97, 95% CI: 0.91–1.03, p = 0.3).
Conclusions - Findings from a high-volume center suggest that, despite the advancements in surgical and postoperative care, EF outcomes after RP have not improved over the last decade. Additional strategies are required to improve EF recovery after RP.
Patient summary - The probability of regaining potency after surgery for prostate cancer did not improve over the last decade; more efforts are needed to improve patient's care after radical prostatectomy.
Background - The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery.
Objective - We examined whether these practice changes have led to observed improvements in EF rates over time.
Design, setting, and participants - We identified 2364 patients treated with either open or minimally-invasive RP at a single academic center in 2008–2015. To mitigate confounding by the surgical learning curve, only patients treated by surgeons who performed at least 100 procedures were considered.
Intervention - EF before and after RP was assessed by the International Index of Erectile Function 6 (IIEF-6), with recovery defined as IIEF-6 ≥24.
Outcome measurements and statistical analysis - We analyzed EF recovery rates of patients treated with bilateral nerve-sparing surgery and free from adjuvant/salvage treatment at the time of EF assessment. Local polynomial regression analyses explored changes in the outcomes over time. Linear and logistic regression analyses were used to estimate the influence of year of surgery on baseline variables and EF recovery.
Results and limitations - We observed a significant decrease over time of the EF recovery rates at both 12 and 24 mo post-RP (all p = 0.01). However, patient's age at surgery increased over time (mean increase of 0.5 per year; p < 0.01), with a resultant increase in risk of comorbidity (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.02–1.15; p = 0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year; p = 0.0003).
After accounting for baseline and pathological characteristics, urinary function, and type of surgery in a multivariable analysis, year of surgery was not associated with EF recovery (12 mo: OR = 0.97, 95% CI: 0.91–1.03, p = 0.4; 24 mo: OR = 0.97, 95% CI: 0.91–1.03, p = 0.3).
Conclusions - Findings from a high-volume center suggest that, despite the advancements in surgical and postoperative care, EF outcomes after RP have not improved over the last decade. Additional strategies are required to improve EF recovery after RP.
Patient summary - The probability of regaining potency after surgery for prostate cancer did not improve over the last decade; more efforts are needed to improve patient's care after radical prostatectomy.
Zhang X, Zhong Y, Saad F, Haider K, Haider A, Xu X. Clinically occult prostate cancer cases may distort the effect of testosterone replacement therapy on risk of PCa. World Journal of Urology 2019. Clinically occult prostate cancer cases may distort the effect of testosterone replacement therapy on risk of PCa
Background - Although prostate cancer (PCa) screening is conducted before testosterone replacement therapy (TRT), clinically occult PCa cases may exist.
Methods - To evaluate whether the possible inclusion of occult PCa cases distorts the effect of TRT on risk of PCa, we followed 776 hypogonadal males (TRT = 400, non-TRT = 376) from a urology center in Germany from 2004 to 2016, with a mean follow-up period of 7 years. We assumed occult cases might take 1–2 years (latency period) to become clinically detectable after receiving TRT. We selected several latency periods (12/18/24 months) and compared the risk of PCa in the TRT and non-TRT group over the latency period, from the end of latency period till the end of follow-up, and over the whole follow-up time.
Results - Overall, 26 PCa cases occurred in the non-TRT group vs 9 cases in the TRT group. Within 18 months of follow-up, 9 cases occurred in the TRT group vs 0 cases in the non-TRT group; from the end of 18 months till the end of follow-up, 26 cases occurred in the non-TRT group vs 0 cases in the TRT group.
The adjusted table showed seemingly adverse effects of TRT on PCa development within 18 months (p = 0.0301) and beneficial effects from the end of 18 months till the end of follow-up (p = 0.0069). Similar patterns were observed for 12 or 24 months as the latency period.
Conclusions - TRT may make occult PCa cases detectable within early phase of treatment and present a beneficial effect in the long run. Future longitudinal studies are needed to confirm findings from our exploratory analyses.
Background - Although prostate cancer (PCa) screening is conducted before testosterone replacement therapy (TRT), clinically occult PCa cases may exist.
Methods - To evaluate whether the possible inclusion of occult PCa cases distorts the effect of TRT on risk of PCa, we followed 776 hypogonadal males (TRT = 400, non-TRT = 376) from a urology center in Germany from 2004 to 2016, with a mean follow-up period of 7 years. We assumed occult cases might take 1–2 years (latency period) to become clinically detectable after receiving TRT. We selected several latency periods (12/18/24 months) and compared the risk of PCa in the TRT and non-TRT group over the latency period, from the end of latency period till the end of follow-up, and over the whole follow-up time.
Results - Overall, 26 PCa cases occurred in the non-TRT group vs 9 cases in the TRT group. Within 18 months of follow-up, 9 cases occurred in the TRT group vs 0 cases in the non-TRT group; from the end of 18 months till the end of follow-up, 26 cases occurred in the non-TRT group vs 0 cases in the TRT group.
The adjusted table showed seemingly adverse effects of TRT on PCa development within 18 months (p = 0.0301) and beneficial effects from the end of 18 months till the end of follow-up (p = 0.0069). Similar patterns were observed for 12 or 24 months as the latency period.
Conclusions - TRT may make occult PCa cases detectable within early phase of treatment and present a beneficial effect in the long run. Future longitudinal studies are needed to confirm findings from our exploratory analyses.
Zhang P, Schatz A, Adeyemi B, et al. Vitamin D and Testosterone Co-ordinately Modulate Intracellular Zinc Levels and Energy Metabolism in Prostate Cancer Cells. The Journal of Steroid Biochemistry and Molecular Biology 2019. https://www.sciencedirect.com/science/article/pii/S0960076018306174
Highlights
· 1,25(OH)2D3, testosterone (T) and 9-cis retinoic acid coordinately modulate energy metabolism in prostate cancer cells
· The metabolic fate of citrate, either used for energy storage or energy production is a critical driver for prostate cancer progression
· 1,25(OH)2D3, testosterone (T) and 9-cis retinoic acid together resets zinc homeostasis in cancer cells to control citrate metabolism that resembles normal prostatic epithelial cells
Vitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early and late invasive PCa was investigated.
BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), retinoid X receptor (RXR).
In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARα) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, Testosterone, and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle metabolism.
1,25(OH)2D3, Testosterone, and 9-cis RA also exert additional control of TCA cycle metabolism by down-regulating SLC25A19, which limits the availability of the co-factor thiamine pyrophosphate (TPP) that is required for enzymatic catalyzation of citrate oxidation. This extensive metabolic reprogramming mediated by 1,25(OH)2D3, Testosterone, and 9-cis RA is preserved in all in vitro cell lines investigated.
These data suggest that 1,25(OH)2D3 and Testosterone are important regulators of normal prostatic energy metabolism. Based on the close association between energy metabolism and cancer progression, supplementation of vitamin D3 and testosterone can restrict the energy production that is required to drive PCa progression by maintaining proper zinc homeostasis and inhibiting TCA cycle activity in PCa cells.
Highlights
· 1,25(OH)2D3, testosterone (T) and 9-cis retinoic acid coordinately modulate energy metabolism in prostate cancer cells
· The metabolic fate of citrate, either used for energy storage or energy production is a critical driver for prostate cancer progression
· 1,25(OH)2D3, testosterone (T) and 9-cis retinoic acid together resets zinc homeostasis in cancer cells to control citrate metabolism that resembles normal prostatic epithelial cells
Vitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early and late invasive PCa was investigated.
BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), retinoid X receptor (RXR).
In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARα) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, Testosterone, and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle metabolism.
1,25(OH)2D3, Testosterone, and 9-cis RA also exert additional control of TCA cycle metabolism by down-regulating SLC25A19, which limits the availability of the co-factor thiamine pyrophosphate (TPP) that is required for enzymatic catalyzation of citrate oxidation. This extensive metabolic reprogramming mediated by 1,25(OH)2D3, Testosterone, and 9-cis RA is preserved in all in vitro cell lines investigated.
These data suggest that 1,25(OH)2D3 and Testosterone are important regulators of normal prostatic energy metabolism. Based on the close association between energy metabolism and cancer progression, supplementation of vitamin D3 and testosterone can restrict the energy production that is required to drive PCa progression by maintaining proper zinc homeostasis and inhibiting TCA cycle activity in PCa cells.
Watt MJ, Clark AK, Selth LA, et al. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer. Science Translational Medicine 2019;11:eaau5758. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer
Prostate cancer is one of the most common tumors in men. Although characterized by slow growth rate, preventing prostate cancer progression to an aggressive stage is a major challenge. Watt et al. focused on cancer metabolism and showed increased fatty acid uptake in human malignant prostate cancer tissue. The increased uptake was mediated by up-regulation of the fatty acid translocase CD36. Silencing CD36 in human prostate cancer cells reduced fatty acid uptake and cell proliferation. In prostate cancer mouse and human preclinical models, Cd36 ablation or inhibition reduced prostate cancer severity. The data suggest that CD36 might be targeted for treating prostate cancer.
Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting Cd36 in the prostate of cancer-susceptible Pten−/− mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.
Prostate cancer is one of the most common tumors in men. Although characterized by slow growth rate, preventing prostate cancer progression to an aggressive stage is a major challenge. Watt et al. focused on cancer metabolism and showed increased fatty acid uptake in human malignant prostate cancer tissue. The increased uptake was mediated by up-regulation of the fatty acid translocase CD36. Silencing CD36 in human prostate cancer cells reduced fatty acid uptake and cell proliferation. In prostate cancer mouse and human preclinical models, Cd36 ablation or inhibition reduced prostate cancer severity. The data suggest that CD36 might be targeted for treating prostate cancer.
Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting Cd36 in the prostate of cancer-susceptible Pten−/− mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.
Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen
PURPOSE: Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information.
MATERIALS AND METHODS: We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study.
A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above.
RESULTS: The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined.
CONCLUSIONS: Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.
Li-Sheng Chen S, Ching-Yuan Fann J, Sipeky C, et al. Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen. The Journal of urology 2019;201:486-95. American Urological Association
PURPOSE: Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information.
MATERIALS AND METHODS: We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study.
A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above.
RESULTS: The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined.
CONCLUSIONS: Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.
Li-Sheng Chen S, Ching-Yuan Fann J, Sipeky C, et al. Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen. The Journal of urology 2019;201:486-95. American Urological Association
Serum Testosterone Levels and Prostate Cancer Risk: A Single Post-Hoc Testosterone Measurement is Not Informative
THE controversy over the relationship between serum testosterone (T) levels and prostate cancer risk is not new. A literature review from 1994 to 2014 identified 45 articles that examined the issue, of which 18 showed a relationship between low serum T and prostate cancer, 17 exhibited a link between high serum T and prostate cancer, and 10 showed no relationship. There are few conditions for which there is such a large body of contradictory evidence.
...
Loughlin KR. Serum Testosterone Levels and Prostate Cancer Risk: A Single Post-Hoc Testosterone Measurement is Not Informative. The Journal of urology 2019;201:40-1. American Urological Association
THE controversy over the relationship between serum testosterone (T) levels and prostate cancer risk is not new. A literature review from 1994 to 2014 identified 45 articles that examined the issue, of which 18 showed a relationship between low serum T and prostate cancer, 17 exhibited a link between high serum T and prostate cancer, and 10 showed no relationship. There are few conditions for which there is such a large body of contradictory evidence.
...
Loughlin KR. Serum Testosterone Levels and Prostate Cancer Risk: A Single Post-Hoc Testosterone Measurement is Not Informative. The Journal of urology 2019;201:40-1. American Urological Association
[OA] Miah S, Tharakan T, Gallagher KA, et al. The effects of testosterone replacement therapy on the prostate: a clinical perspective. F1000Research 2019;8. The effects of testosterone replacement therapy on the prostate: a clinical perspective - F1000Research
Male hypogonadism is a clinical syndrome characterized by low testosterone and symptoms of androgen deficiency. Prostate cancer remains a significant health burden and cause of male mortality worldwide. The use of testosterone replacement therapy drugs is rising year-on-year for the treatment of androgen deficiency and has reached global proportions. As clinicians, we must be well versed and provide appropriate counseling for men prior to the commencement of testosterone replacement therapy.
This review summarizes the current clinical and basic science evidence in relation to this commonly encountered clinical scenario. There is gathering evidence that suggests, from an oncological perspective, that it is safe to commence testosterone replacement therapy for men who have a combination of biochemically confirmed androgen deficiency and who have either had definitive treatment of their prostate cancer or no previous history of this disease.
However, patients must be made aware and cautioned that there is a distinct lack of level 1 evidence. Calls for such studies have been made throughout the urological and andrological community to provide a definitive answer. For those with a diagnosis of prostate cancer that remains untreated, there is a sparsity of evidence and therefore clinicians are "pushing the limits" of safety when considering the commencement of testosterone replacement therapy.
Male hypogonadism is a clinical syndrome characterized by low testosterone and symptoms of androgen deficiency. Prostate cancer remains a significant health burden and cause of male mortality worldwide. The use of testosterone replacement therapy drugs is rising year-on-year for the treatment of androgen deficiency and has reached global proportions. As clinicians, we must be well versed and provide appropriate counseling for men prior to the commencement of testosterone replacement therapy.
This review summarizes the current clinical and basic science evidence in relation to this commonly encountered clinical scenario. There is gathering evidence that suggests, from an oncological perspective, that it is safe to commence testosterone replacement therapy for men who have a combination of biochemically confirmed androgen deficiency and who have either had definitive treatment of their prostate cancer or no previous history of this disease.
However, patients must be made aware and cautioned that there is a distinct lack of level 1 evidence. Calls for such studies have been made throughout the urological and andrological community to provide a definitive answer. For those with a diagnosis of prostate cancer that remains untreated, there is a sparsity of evidence and therefore clinicians are "pushing the limits" of safety when considering the commencement of testosterone replacement therapy.
Prostate Cancer (PCa) Incidence and Severity in 821 Hypogonadal Men with and without Testosterone Therapy (TTh) in a Controlled, Observational Registry Implying More Than 7,000 Patient-Years
Background: Guidelines by AUA and EAU state that there is no evidence for an increased PCa risk for testosterone (T) treatment in hypogonadal men.
Methods: In a registry study initiated in 2004 in a urology practice, 428 hypogonadal men (T≤350 ng/dL) received T undecanoate 1000 mg every 3 months following an initial 6-month interval for up to 13 years (T-group). 393 hypogonadal men (age range 51-74) opted against TTh (CTRL).
Suspicion of or active PCa was excluded by transrectal ultrasound, digital rectal examination and PSA before treatment/observation initiation. Examinations were repeated between one and four times per year. Biopsies were performed when indicated according to EAU Guidelines.
Results: In the T-group, 12 (2.8%), in CTRL, 42 men (10.9%) were diagnosed with PCa. The mean baseline age of PCa patients was 64.9 years in the T-group and 64 in CTRL.
In the T-group, the average time span between day of first injection and positive biopsy was 14.2 months (range: 5-18). No patient was diagnosed with PCa beyond 18 months of TTh. In CTRL, PCa was diagnosed at any time during the observation time.
In the T-group, radical prostatectomy (RP) was performed in all men. All but 3 patients had Gleason score (GS) ≤6, and all but 1 had a primary GS of 3. Tumor grade was G2 in all 12 (100%), tumor stage T2a in 7 (58%), T2b in 3 (25%), and T2c in 2 (17%) patients. All but 2 patients are back on TTh after an average time of 25 months.
In CTRL, RP was performed in all but 6 patients who received radiation therapy (RT). GS was ≤6 in 2 patients, 7 men had a GS of 7, 21 a GS of 8, and 12 a GS of 9. 4 men had a primary Gleason score of 3, 29 had 4, and 9 had 5. Tumor grade was G2 in 9 (21%) and G3 in 33 (79%) patients, tumor stage T2a in 2 (5%), T2c in 1 (2%), T3b in 15 (36%) and T3c in 24 (57%) patients.
In CTRL, biochemical recurrence occurred in 11 (26%) patients. These patients received androgen deprivation therapy (ADT). 12 (34%) patients died of whom 7 were on ADT. In the T-group, no biochemical recurrences or deaths occurred during the observation time.
Conclusions: LESS PCa OCCURRED AND SEVERITY WAS LOWER IN TESTOSTERONE-TREATED HYPOGONADAL PATIENTS COMPARED TO UNTREATED HYPOGONADAL CONTROLS.
Haider A, Haider KS. Prostate cancer (PCa) incidence and severity in 821 hypogonadal men with and without testosterone therapy (TTh) in a controlled, observational registry implying more than 7,000 patient-years. Journal of Clinical Oncology 2019;37:304-. http://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.304
Background: Guidelines by AUA and EAU state that there is no evidence for an increased PCa risk for testosterone (T) treatment in hypogonadal men.
Methods: In a registry study initiated in 2004 in a urology practice, 428 hypogonadal men (T≤350 ng/dL) received T undecanoate 1000 mg every 3 months following an initial 6-month interval for up to 13 years (T-group). 393 hypogonadal men (age range 51-74) opted against TTh (CTRL).
Suspicion of or active PCa was excluded by transrectal ultrasound, digital rectal examination and PSA before treatment/observation initiation. Examinations were repeated between one and four times per year. Biopsies were performed when indicated according to EAU Guidelines.
Results: In the T-group, 12 (2.8%), in CTRL, 42 men (10.9%) were diagnosed with PCa. The mean baseline age of PCa patients was 64.9 years in the T-group and 64 in CTRL.
In the T-group, the average time span between day of first injection and positive biopsy was 14.2 months (range: 5-18). No patient was diagnosed with PCa beyond 18 months of TTh. In CTRL, PCa was diagnosed at any time during the observation time.
In the T-group, radical prostatectomy (RP) was performed in all men. All but 3 patients had Gleason score (GS) ≤6, and all but 1 had a primary GS of 3. Tumor grade was G2 in all 12 (100%), tumor stage T2a in 7 (58%), T2b in 3 (25%), and T2c in 2 (17%) patients. All but 2 patients are back on TTh after an average time of 25 months.
In CTRL, RP was performed in all but 6 patients who received radiation therapy (RT). GS was ≤6 in 2 patients, 7 men had a GS of 7, 21 a GS of 8, and 12 a GS of 9. 4 men had a primary Gleason score of 3, 29 had 4, and 9 had 5. Tumor grade was G2 in 9 (21%) and G3 in 33 (79%) patients, tumor stage T2a in 2 (5%), T2c in 1 (2%), T3b in 15 (36%) and T3c in 24 (57%) patients.
In CTRL, biochemical recurrence occurred in 11 (26%) patients. These patients received androgen deprivation therapy (ADT). 12 (34%) patients died of whom 7 were on ADT. In the T-group, no biochemical recurrences or deaths occurred during the observation time.
Conclusions: LESS PCa OCCURRED AND SEVERITY WAS LOWER IN TESTOSTERONE-TREATED HYPOGONADAL PATIENTS COMPARED TO UNTREATED HYPOGONADAL CONTROLS.
Haider A, Haider KS. Prostate cancer (PCa) incidence and severity in 821 hypogonadal men with and without testosterone therapy (TTh) in a controlled, observational registry implying more than 7,000 patient-years. Journal of Clinical Oncology 2019;37:304-. http://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.304
Impact of Testosterone Replacement Therapy After Radiation Therapy on Prostate Cancer Outcomes
Background: Currently there is little data to guide the use of testosterone replacement therapy in prostate cancer patients who have received radiation therapy (RT). We sought to evaluate the impact of post-RT testosterone replacement on prostate cancer outcomes in a large national cohort.
Methods: We conducted a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure. We identified node-negative and non-metastatic prostate cancer patients diagnosed between 2001-2015 treated with RT. We excluded patients for missing covariate and follow-up data.
Receipt of testosterone was coded as a time-dependent covariate. Other covariates included: age, Charlson Comorbidity index, diagnosis year, body mass index, race, PSA, clinical T/N/M stage, Gleason score, and receipt of hormone therapy. We evaluated prostate cancer-specific survival, overall survival, and biochemical recurrence free survival using multivariable Cox regression.
Results: Our cohort included 41,544 patients, of whom 544 (1.3%) received testosterone replacement after RT. There were no differences in Charlson comorbidity, clinical T stage, median pre-treatment PSA or Gleason score between treatment groups.
Testosterone patients were more likely to be of younger age, non-black, have a lower median post-treatment PSA nadir (0.1 vs. 0.2; p < 0.001), have higher BMI, and have used hormone therapy (46.7% vs 40.3%; p = 0.003).
Median duration of ADT usage was equivalent between treatment groups (testosterone: 185 days vs. non-testosterone: 186 days, p = 0.77). The median time from RT to TRT was 3.52 years.
After controlling for differences in covariates between treatment groups, we found no difference in prostate cancer specific mortality (HR 1.02; 95% CI 0.62-1.67; p = 0.95), overall survival (HR 1.02; 95% CI 0.84-1.24; p = 0.86), non-cancer mortality (HR 1.02; 95% CI 0.82-1.27; p = 0.86) biochemical recurrence free survival (HR 1.07; 95% CI 0.90-1.28; p = 0.45).
Conclusions: Our results suggest that testosterone replacement is safe in prostate cancer patients who have received RT. Prospective data are required to confirm the safety of post-RT testosterone replacement.
Sarkar R, Parsons JK, Einck JP, et al. Impact of testosterone replacement therapy after radiation therapy on prostate cancer outcomes. Journal of Clinical Oncology 2019;37:99-. http://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.99
Background: Currently there is little data to guide the use of testosterone replacement therapy in prostate cancer patients who have received radiation therapy (RT). We sought to evaluate the impact of post-RT testosterone replacement on prostate cancer outcomes in a large national cohort.
Methods: We conducted a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure. We identified node-negative and non-metastatic prostate cancer patients diagnosed between 2001-2015 treated with RT. We excluded patients for missing covariate and follow-up data.
Receipt of testosterone was coded as a time-dependent covariate. Other covariates included: age, Charlson Comorbidity index, diagnosis year, body mass index, race, PSA, clinical T/N/M stage, Gleason score, and receipt of hormone therapy. We evaluated prostate cancer-specific survival, overall survival, and biochemical recurrence free survival using multivariable Cox regression.
Results: Our cohort included 41,544 patients, of whom 544 (1.3%) received testosterone replacement after RT. There were no differences in Charlson comorbidity, clinical T stage, median pre-treatment PSA or Gleason score between treatment groups.
Testosterone patients were more likely to be of younger age, non-black, have a lower median post-treatment PSA nadir (0.1 vs. 0.2; p < 0.001), have higher BMI, and have used hormone therapy (46.7% vs 40.3%; p = 0.003).
Median duration of ADT usage was equivalent between treatment groups (testosterone: 185 days vs. non-testosterone: 186 days, p = 0.77). The median time from RT to TRT was 3.52 years.
After controlling for differences in covariates between treatment groups, we found no difference in prostate cancer specific mortality (HR 1.02; 95% CI 0.62-1.67; p = 0.95), overall survival (HR 1.02; 95% CI 0.84-1.24; p = 0.86), non-cancer mortality (HR 1.02; 95% CI 0.82-1.27; p = 0.86) biochemical recurrence free survival (HR 1.07; 95% CI 0.90-1.28; p = 0.45).
Conclusions: Our results suggest that testosterone replacement is safe in prostate cancer patients who have received RT. Prospective data are required to confirm the safety of post-RT testosterone replacement.
Sarkar R, Parsons JK, Einck JP, et al. Impact of testosterone replacement therapy after radiation therapy on prostate cancer outcomes. Journal of Clinical Oncology 2019;37:99-. http://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.99
Impact of Testosterone Replacement Therapy After Radical Prostatectomy on Prostate Cancer Outcomes
Background: Currently there is little data to guide the use of post-radical prostatectomy (RP) testosterone replacement therapy in prostate cancer. We sought to evaluate the impact of post-RP testosterone replacement on prostate cancer outcomes in a large national cohort.
Methods: We conducted a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure. We identified node-negative and non-metastatic prostate cancer patients diagnosed between 2001-2015 treated with RP. We excluded patients for missing covariate and follow-up data.
We then coded receipt of testosterone replacement after RP as a time-dependent covariate. Other covariates included: age, Charlson Comorbidity index, diagnosis year, body mass index, race, PSA, clinical T/N/M stage, Gleason score, and receipt of hormone therapy.
Biochemical recurrence was defined as a post-RP PSA≥0.2. We evaluated prostate cancer-specific survival, overall survival, and biochemical recurrence free survival using multivariable Cox regression.
Results: Our cohort included 28,651 patients, of whom 469 (1.6%) received testosterone replacement after RP. Median follow up was 7.4 years.
There were no differences in clinical T stage, median post-RP PSA (testosterone: 0 non-testosterone: 0; p = 0.18), or hormone therapy use between treatment groups.
Testosterone patients were more likely to be of younger age, have higher comorbidity, non-black, have a lower median pre-treatment PSA (5.0 vs 5.8; p < 0.001), and have higher BMI. The median time from RP to TRT was 3.0 years.
After controlling for potential confounders, we found no difference in prostate cancer specific mortality (HR 0.73; 95% CI 0.32-1.62; p = 0.43), overall survival (HR 1.11; 95% CI 0.86-1.44; p = 0.43), non-cancer mortality (HR 1.17; 95% CI 0.89-1.55; p = 0.26) biochemical recurrence free survival (HR 1.07; 95% CI 0.84-1.36; p = 0.59) between testosterone users and non-users.
Conclusions: Our results suggest that testosterone replacement is safe in prostate cancer patients who have undergone RP, though prospective data is necessary to confirm this finding.
Sarkar R, Parsons JK, Einck JP, et al. Impact of testosterone replacement therapy after radical prostatectomy on prostate cancer outcomes. Journal of Clinical Oncology 2019;37:100-. http://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.100
Background: Currently there is little data to guide the use of post-radical prostatectomy (RP) testosterone replacement therapy in prostate cancer. We sought to evaluate the impact of post-RP testosterone replacement on prostate cancer outcomes in a large national cohort.
Methods: We conducted a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure. We identified node-negative and non-metastatic prostate cancer patients diagnosed between 2001-2015 treated with RP. We excluded patients for missing covariate and follow-up data.
We then coded receipt of testosterone replacement after RP as a time-dependent covariate. Other covariates included: age, Charlson Comorbidity index, diagnosis year, body mass index, race, PSA, clinical T/N/M stage, Gleason score, and receipt of hormone therapy.
Biochemical recurrence was defined as a post-RP PSA≥0.2. We evaluated prostate cancer-specific survival, overall survival, and biochemical recurrence free survival using multivariable Cox regression.
Results: Our cohort included 28,651 patients, of whom 469 (1.6%) received testosterone replacement after RP. Median follow up was 7.4 years.
There were no differences in clinical T stage, median post-RP PSA (testosterone: 0 non-testosterone: 0; p = 0.18), or hormone therapy use between treatment groups.
Testosterone patients were more likely to be of younger age, have higher comorbidity, non-black, have a lower median pre-treatment PSA (5.0 vs 5.8; p < 0.001), and have higher BMI. The median time from RP to TRT was 3.0 years.
After controlling for potential confounders, we found no difference in prostate cancer specific mortality (HR 0.73; 95% CI 0.32-1.62; p = 0.43), overall survival (HR 1.11; 95% CI 0.86-1.44; p = 0.43), non-cancer mortality (HR 1.17; 95% CI 0.89-1.55; p = 0.26) biochemical recurrence free survival (HR 1.07; 95% CI 0.84-1.36; p = 0.59) between testosterone users and non-users.
Conclusions: Our results suggest that testosterone replacement is safe in prostate cancer patients who have undergone RP, though prospective data is necessary to confirm this finding.
Sarkar R, Parsons JK, Einck JP, et al. Impact of testosterone replacement therapy after radical prostatectomy on prostate cancer outcomes. Journal of Clinical Oncology 2019;37:100-. http://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.100
Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report
We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART.
After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.
Sunada T, Hama Y, Ikeuchi R, et al. [Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report]. Hinyokika kiyo Acta urologica Japonica 2018;64:501-4. [Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report]. - PubMed - NCBI
We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART.
After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.
Sunada T, Hama Y, Ikeuchi R, et al. [Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report]. Hinyokika kiyo Acta urologica Japonica 2018;64:501-4. [Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report]. - PubMed - NCBI
Zhang X, Zhong Y, Saad F, et al. Testosterone therapy may reduce prostate cancer risk due to testosterone deficiency at a young age via stabilizing serum testosterone levels. The aging male: the official journal of the International Society for the Study of the Aging Male 2019:1-7. https://www.tandfonline.com/doi/abs/10.1080/13685538.2019.1578739?journalCode=itam20
OBJECTIVES: To investigate whether testosterone replacement therapy (TRT) reduces prostate cancer (PCa) risk via stabilizing serum testosterone (T) levels beyond simply elevating serum T levels and whether TRT reduces PCa risk due to low serum T levels at a young age.
METHODS: We analyzed data of 776 hypogonadal men from a urology center in Bremerhaven, Germany through 2004-2016 to investigate whether the TRT group has more stable T levels and whether TRT can reduce the risk of PCa due to low serum T levels at an early age. We derived an index, Maximum Decline of T Relative to Baseline (MDRB), to describe the magnitude of T declines and variations over time.
RESULTS: We found the TRT group has more stable serum T levels (e.g. smaller drop-offs) during the follow-up period as compared to the non-TRT group, and the mean of MDRB is significantly higher in the untreated group (1.553 nmol/L VS 0.013 nmol/L; p-value < .001). TRT significantly reduces the risk of PCa associated with T deficiency at a young age (p-value = .00087).
CONCLUSIONS: TRT may reduce PCa risk via maintaining serum T levels within individual's normal range; T surveillance may be needed for males who have low serum T levels at a young age to monitor abnormal variations of T levels and ensure timely treatment when necessary to reduce PCa risk.
OBJECTIVES: To investigate whether testosterone replacement therapy (TRT) reduces prostate cancer (PCa) risk via stabilizing serum testosterone (T) levels beyond simply elevating serum T levels and whether TRT reduces PCa risk due to low serum T levels at a young age.
METHODS: We analyzed data of 776 hypogonadal men from a urology center in Bremerhaven, Germany through 2004-2016 to investigate whether the TRT group has more stable T levels and whether TRT can reduce the risk of PCa due to low serum T levels at an early age. We derived an index, Maximum Decline of T Relative to Baseline (MDRB), to describe the magnitude of T declines and variations over time.
RESULTS: We found the TRT group has more stable serum T levels (e.g. smaller drop-offs) during the follow-up period as compared to the non-TRT group, and the mean of MDRB is significantly higher in the untreated group (1.553 nmol/L VS 0.013 nmol/L; p-value < .001). TRT significantly reduces the risk of PCa associated with T deficiency at a young age (p-value = .00087).
CONCLUSIONS: TRT may reduce PCa risk via maintaining serum T levels within individual's normal range; T surveillance may be needed for males who have low serum T levels at a young age to monitor abnormal variations of T levels and ensure timely treatment when necessary to reduce PCa risk.
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