Prostate Cancer

Key clinical point: Single nucleotide polymorphisms (SNP) can serve as prognostic factors for prostate cancer

Major finding: In patients with prostate cancer, SNP rs2910164 of miR146a was more common in patients with a Gleason score of 7 or higher than those with a Gleason score of less than 7 (P=0.043); in addition, SNP rs1834306 of miR100 was overexpressed in those with pT3 staging compared to pT2 (P = 0.004).

Study details: The data come from a review of 100 patients with clinically localized prostate cancer who underwent radical prostatectomy and 68 controls without prostate cancer.

Disclosures: The study was supported in part by a grant from the Sao Paulo Research Foundation. The researchers had no financial conflicts to disclose.

Source: Camargo JA et al. Int J Biol Markers. 2021 May 25. doi: 10.1177/172460082199746.

Key clinical point: Single nucleotide polymorphisms (SNP) can serve as prognostic factors for prostate cancer

Major finding: In patients with prostate cancer, SNP rs2910164 of miR146a was more common in patients with a Gleason score of 7 or higher than those with a Gleason score of less than 7 (P=0.043); in addition, SNP rs1834306 of miR100 was overexpressed in those with pT3 staging compared to pT2 (P = 0.004).

Study details: The data come from a review of 100 patients with clinically localized prostate cancer who underwent radical prostatectomy and 68 controls without prostate cancer.

Disclosures: The study was supported in part by a grant from the Sao Paulo Research Foundation. The researchers had no financial conflicts to disclose.

Source: Camargo JA et al. Int J Biol Markers. 2021 May 25. doi: 10.1177/172460082199746.

Key clinical point: Single nucleotide polymorphisms (SNP) can serve as prognostic factors for prostate cancer

Major finding: In patients with prostate cancer, SNP rs2910164 of miR146a was more common in patients with a Gleason score of 7 or higher than those with a Gleason score of less than 7 (P=0.043); in addition, SNP rs1834306 of miR100 was overexpressed in those with pT3 staging compared to pT2 (P = 0.004).

Study details: The data come from a review of 100 patients with clinically localized prostate cancer who underwent radical prostatectomy and 68 controls without prostate cancer.

Disclosures: The study was supported in part by a grant from the Sao Paulo Research Foundation. The researchers had no financial conflicts to disclose.

Source: Camargo JA et al. Int J Biol Markers. 2021 May 25. doi: 10.1177/172460082199746.

Key clinical point: Increased bone involvement was negatively correlated with overall survival after radioligand therapy for prostate cancer.

Major finding: The median overall survival for prostate cancer patients with less than 6 bone lesions, 6-20 lesions, more than 20 lesions, and diffuse lesions was 18 months, 13 months, 11 months, and 8 months, respectively.

Study details: The data come from 319 men with progressive metastatic castration-resistant prostate cancer who underwent radioligand therapy with lutetium prostate-specific membrane antigen (Lu-PSMA-617).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ahmadzadehfar H et al. Eur J Nucl Med Mol Imaging. 2021 May 25. doi: 10.1007/s00259-021-05383-3.

Key clinical point: Increased bone involvement was negatively correlated with overall survival after radioligand therapy for prostate cancer.

Major finding: The median overall survival for prostate cancer patients with less than 6 bone lesions, 6-20 lesions, more than 20 lesions, and diffuse lesions was 18 months, 13 months, 11 months, and 8 months, respectively.

Study details: The data come from 319 men with progressive metastatic castration-resistant prostate cancer who underwent radioligand therapy with lutetium prostate-specific membrane antigen (Lu-PSMA-617).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ahmadzadehfar H et al. Eur J Nucl Med Mol Imaging. 2021 May 25. doi: 10.1007/s00259-021-05383-3.

Key clinical point: Increased bone involvement was negatively correlated with overall survival after radioligand therapy for prostate cancer.

Major finding: The median overall survival for prostate cancer patients with less than 6 bone lesions, 6-20 lesions, more than 20 lesions, and diffuse lesions was 18 months, 13 months, 11 months, and 8 months, respectively.

Study details: The data come from 319 men with progressive metastatic castration-resistant prostate cancer who underwent radioligand therapy with lutetium prostate-specific membrane antigen (Lu-PSMA-617).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ahmadzadehfar H et al. Eur J Nucl Med Mol Imaging. 2021 May 25. doi: 10.1007/s00259-021-05383-3.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m², high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).
 

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).
 

A counterbalance to genetic risk

Dr. Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

She added that previous research has confirmed physical activity as a protective factor, but more study is needed to shed light on the relative benefit of the healthy lifestyle components.

In addition, further research is necessary to explain why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.

Dr. Plym speculated that the genetic variants contributing to a high PRS may also be the variants that have the strongest interaction with lifestyle factors. For men with a genetic predisposition to prostate cancer, she added, these findings underscore the potential value of surveillance.

“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable,” she said.

Charles Swanton, MBPhD, of the Francis Crick Institute and UCL Cancer Institute in London, raised the possibility that competing risk issues could be at play.

If a healthy lifestyle leads to longer life, he asked, does that make it more likely that patients will live long enough to die from their prostate cancer because they are not dying from cardiovascular disease, complications of diabetes, etc.? In that case, is the healthy lifestyle really affecting prostate cancer at all?

Dr. Plym responded that, among those in the highest genetic risk group with an unhealthy lifestyle, the increased risk for prostate cancer exceeded the risk for other illnesses.

This study was funded by the DiNovi Family Foundation, the National Cancer Institute, the William Casey Foundation, the Swedish Society for Medical Research, and the Prostate Cancer Foundation. Dr. Plym declared no conflicts of interest. Dr. Swanton disclosed relationships with numerous companies, including Pfizer, Novartis, and GlaxoSmithKline.

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m², high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).
 

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).
 

A counterbalance to genetic risk

Dr. Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

She added that previous research has confirmed physical activity as a protective factor, but more study is needed to shed light on the relative benefit of the healthy lifestyle components.

In addition, further research is necessary to explain why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.

Dr. Plym speculated that the genetic variants contributing to a high PRS may also be the variants that have the strongest interaction with lifestyle factors. For men with a genetic predisposition to prostate cancer, she added, these findings underscore the potential value of surveillance.

“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable,” she said.

Charles Swanton, MBPhD, of the Francis Crick Institute and UCL Cancer Institute in London, raised the possibility that competing risk issues could be at play.

If a healthy lifestyle leads to longer life, he asked, does that make it more likely that patients will live long enough to die from their prostate cancer because they are not dying from cardiovascular disease, complications of diabetes, etc.? In that case, is the healthy lifestyle really affecting prostate cancer at all?

Dr. Plym responded that, among those in the highest genetic risk group with an unhealthy lifestyle, the increased risk for prostate cancer exceeded the risk for other illnesses.

This study was funded by the DiNovi Family Foundation, the National Cancer Institute, the William Casey Foundation, the Swedish Society for Medical Research, and the Prostate Cancer Foundation. Dr. Plym declared no conflicts of interest. Dr. Swanton disclosed relationships with numerous companies, including Pfizer, Novartis, and GlaxoSmithKline.

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m², high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).
 

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).
 

A counterbalance to genetic risk

Dr. Plym observed that the rate of lethal disease in men with the best lifestyle scores matched the rate for the study population as a whole (3%), suggesting that healthy lifestyle may counterbalance high genetic risk.

She added that previous research has confirmed physical activity as a protective factor, but more study is needed to shed light on the relative benefit of the healthy lifestyle components.

In addition, further research is necessary to explain why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.

Dr. Plym speculated that the genetic variants contributing to a high PRS may also be the variants that have the strongest interaction with lifestyle factors. For men with a genetic predisposition to prostate cancer, she added, these findings underscore the potential value of surveillance.

“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable,” she said.

Charles Swanton, MBPhD, of the Francis Crick Institute and UCL Cancer Institute in London, raised the possibility that competing risk issues could be at play.

If a healthy lifestyle leads to longer life, he asked, does that make it more likely that patients will live long enough to die from their prostate cancer because they are not dying from cardiovascular disease, complications of diabetes, etc.? In that case, is the healthy lifestyle really affecting prostate cancer at all?

Dr. Plym responded that, among those in the highest genetic risk group with an unhealthy lifestyle, the increased risk for prostate cancer exceeded the risk for other illnesses.

This study was funded by the DiNovi Family Foundation, the National Cancer Institute, the William Casey Foundation, the Swedish Society for Medical Research, and the Prostate Cancer Foundation. Dr. Plym declared no conflicts of interest. Dr. Swanton disclosed relationships with numerous companies, including Pfizer, Novartis, and GlaxoSmithKline.