Mark Klein, MD

            Kishan et al conducted a meta-analysis to evaluate the relative effects of the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) on metastasis-free survival (MFS) in patients with localized prostate cancer in the following three settings: 1) RT alone versus RT plus adjuvant ADT, 2) extension of ADT duration in the neoadjuvant setting before RT, and 3) extension of adjuvant ADT duration. MFS was increased in the adjuvant ADT setting, and prolongation of ADT duration was associated with a higher MFS than shorter duration. However, extension of neoadjuvant ADT was not associated with a higher MFS compared to a shorter duration. The meta-analysis further supports a longer versus shorter ADT duration, but it does not support a longer neoadjuvant ADT duration.

            To determine the effects of salvage RT on outcomes in the setting of biochemical relapse, Tilki et al conducted a retrospective cohort analysis of a multi-institutional database of patients with biochemical recurrence after radical prostatectomy (RP). MFS at 15 years post-RP was 84.3% in the RT group and 76.9% in the non-RT group, while overall survival (OS), also at 15 years post-RP, was 85.3% in the RT group versus 74.4% in the non-RT group (both analyses were statistically significant). While supportive of salvage RT, there was no data on prostate-specific antigen (PSA) doubling times, nor was it possible to control for imaging modality. It is possible that newer prostate-specific membrane antigen (PSMA)-based positron emission tomography imaging may affect MFS in studies such as these.

            Prostatectomy (with or without lymph node dissection), external beam RT (EBRT) with  ADT, or EBRT with brachytherapy (BT) with or without ADT are options in unfavorable intermediate-risk prostate cancer. The optimal use of BT in localized prostate cancer is somewhat uncertain, especially across the risk spectrum. Andruska et al conducted an analysis of the National Cancer Database (NCDB) to evaluate whether EBRT plus BT with or without ADT results in an improvement in overall survival (OS) compared with BT with or without ADT. OS was higher for the EBRT plus BT groups; however, when the ADT + EBRT + BT group was compared with EBRT + BT without ADT group, the improvement in OS was not statistically significant. Overall, the analysis favored EBRT + BT over BT alone, further supporting current guidelines.

            Kishan et al conducted a meta-analysis to evaluate the relative effects of the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) on metastasis-free survival (MFS) in patients with localized prostate cancer in the following three settings: 1) RT alone versus RT plus adjuvant ADT, 2) extension of ADT duration in the neoadjuvant setting before RT, and 3) extension of adjuvant ADT duration. MFS was increased in the adjuvant ADT setting, and prolongation of ADT duration was associated with a higher MFS than shorter duration. However, extension of neoadjuvant ADT was not associated with a higher MFS compared to a shorter duration. The meta-analysis further supports a longer versus shorter ADT duration, but it does not support a longer neoadjuvant ADT duration.

            To determine the effects of salvage RT on outcomes in the setting of biochemical relapse, Tilki et al conducted a retrospective cohort analysis of a multi-institutional database of patients with biochemical recurrence after radical prostatectomy (RP). MFS at 15 years post-RP was 84.3% in the RT group and 76.9% in the non-RT group, while overall survival (OS), also at 15 years post-RP, was 85.3% in the RT group versus 74.4% in the non-RT group (both analyses were statistically significant). While supportive of salvage RT, there was no data on prostate-specific antigen (PSA) doubling times, nor was it possible to control for imaging modality. It is possible that newer prostate-specific membrane antigen (PSMA)-based positron emission tomography imaging may affect MFS in studies such as these.

            Prostatectomy (with or without lymph node dissection), external beam RT (EBRT) with  ADT, or EBRT with brachytherapy (BT) with or without ADT are options in unfavorable intermediate-risk prostate cancer. The optimal use of BT in localized prostate cancer is somewhat uncertain, especially across the risk spectrum. Andruska et al conducted an analysis of the National Cancer Database (NCDB) to evaluate whether EBRT plus BT with or without ADT results in an improvement in overall survival (OS) compared with BT with or without ADT. OS was higher for the EBRT plus BT groups; however, when the ADT + EBRT + BT group was compared with EBRT + BT without ADT group, the improvement in OS was not statistically significant. Overall, the analysis favored EBRT + BT over BT alone, further supporting current guidelines.

            Kishan et al conducted a meta-analysis to evaluate the relative effects of the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) on metastasis-free survival (MFS) in patients with localized prostate cancer in the following three settings: 1) RT alone versus RT plus adjuvant ADT, 2) extension of ADT duration in the neoadjuvant setting before RT, and 3) extension of adjuvant ADT duration. MFS was increased in the adjuvant ADT setting, and prolongation of ADT duration was associated with a higher MFS than shorter duration. However, extension of neoadjuvant ADT was not associated with a higher MFS compared to a shorter duration. The meta-analysis further supports a longer versus shorter ADT duration, but it does not support a longer neoadjuvant ADT duration.

            To determine the effects of salvage RT on outcomes in the setting of biochemical relapse, Tilki et al conducted a retrospective cohort analysis of a multi-institutional database of patients with biochemical recurrence after radical prostatectomy (RP). MFS at 15 years post-RP was 84.3% in the RT group and 76.9% in the non-RT group, while overall survival (OS), also at 15 years post-RP, was 85.3% in the RT group versus 74.4% in the non-RT group (both analyses were statistically significant). While supportive of salvage RT, there was no data on prostate-specific antigen (PSA) doubling times, nor was it possible to control for imaging modality. It is possible that newer prostate-specific membrane antigen (PSMA)-based positron emission tomography imaging may affect MFS in studies such as these.

            Prostatectomy (with or without lymph node dissection), external beam RT (EBRT) with  ADT, or EBRT with brachytherapy (BT) with or without ADT are options in unfavorable intermediate-risk prostate cancer. The optimal use of BT in localized prostate cancer is somewhat uncertain, especially across the risk spectrum. Andruska et al conducted an analysis of the National Cancer Database (NCDB) to evaluate whether EBRT plus BT with or without ADT results in an improvement in overall survival (OS) compared with BT with or without ADT. OS was higher for the EBRT plus BT groups; however, when the ADT + EBRT + BT group was compared with EBRT + BT without ADT group, the improvement in OS was not statistically significant. Overall, the analysis favored EBRT + BT over BT alone, further supporting current guidelines.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

Extensive efforts have been put forth to evaluate which patients may safely delay, or completely avoid, treatment for prostate cancer. However, identifying who can safely avoid treatment is challenging. Arcot et al. utilized the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for men to determine whether those with prostate cancer grade group 1 with delayed treatment had increased need for secondary treatments, such as androgen deprivation or radiation therapy, compared with those with upfront surgery. There was a small decrease in the probability of being free from secondary treatment 24 months after diagnosis (96% vs. 93%), suggesting that such an approach is quite reasonable.

These two studies exemplify one of the ongoing points of discussion in treatment of early stage prostate cancer: whether upfront treatments are of net benefit for patients. The study by Wallis et al. further evaluated this point by conducting a prospective cohort study to evaluate the extent of regret of choice of treatment strategy amongst patients with prostate cancer. Out of this cohort of 2,072 men, 16% who underwent surgery, 11% who received radiation, and 7% who chose active surveillance reported regret regarding the treatment choice. However, when controlled for functional outcomes, the differences amongst treatment modalities were not statistically significant. However, perceived treatment efficacy and adverse effects were associated with regret when compared with patient expectations prior to treatment. This suggest that research and focus on shared decision-making in the clinic may be highly beneficial.

Extensive efforts have been put forth to evaluate which patients may safely delay, or completely avoid, treatment for prostate cancer. However, identifying who can safely avoid treatment is challenging. Arcot et al. utilized the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for men to determine whether those with prostate cancer grade group 1 with delayed treatment had increased need for secondary treatments, such as androgen deprivation or radiation therapy, compared with those with upfront surgery. There was a small decrease in the probability of being free from secondary treatment 24 months after diagnosis (96% vs. 93%), suggesting that such an approach is quite reasonable.

These two studies exemplify one of the ongoing points of discussion in treatment of early stage prostate cancer: whether upfront treatments are of net benefit for patients. The study by Wallis et al. further evaluated this point by conducting a prospective cohort study to evaluate the extent of regret of choice of treatment strategy amongst patients with prostate cancer. Out of this cohort of 2,072 men, 16% who underwent surgery, 11% who received radiation, and 7% who chose active surveillance reported regret regarding the treatment choice. However, when controlled for functional outcomes, the differences amongst treatment modalities were not statistically significant. However, perceived treatment efficacy and adverse effects were associated with regret when compared with patient expectations prior to treatment. This suggest that research and focus on shared decision-making in the clinic may be highly beneficial.

Extensive efforts have been put forth to evaluate which patients may safely delay, or completely avoid, treatment for prostate cancer. However, identifying who can safely avoid treatment is challenging. Arcot et al. utilized the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for men to determine whether those with prostate cancer grade group 1 with delayed treatment had increased need for secondary treatments, such as androgen deprivation or radiation therapy, compared with those with upfront surgery. There was a small decrease in the probability of being free from secondary treatment 24 months after diagnosis (96% vs. 93%), suggesting that such an approach is quite reasonable.

These two studies exemplify one of the ongoing points of discussion in treatment of early stage prostate cancer: whether upfront treatments are of net benefit for patients. The study by Wallis et al. further evaluated this point by conducting a prospective cohort study to evaluate the extent of regret of choice of treatment strategy amongst patients with prostate cancer. Out of this cohort of 2,072 men, 16% who underwent surgery, 11% who received radiation, and 7% who chose active surveillance reported regret regarding the treatment choice. However, when controlled for functional outcomes, the differences amongst treatment modalities were not statistically significant. However, perceived treatment efficacy and adverse effects were associated with regret when compared with patient expectations prior to treatment. This suggest that research and focus on shared decision-making in the clinic may be highly beneficial.

            Racial and ethnic disparities in prostate cancer diagnosis and treatment are well recognized. Prostate magnetic resonance imaging (MRI) as part of a diagnostic approach for people with elevated PSA may decrease unnecessary biopsies or better direct biopsies based on results, and its use is increasing significantly. Abashidze et al examined Medicare claims between 2011 and 2017 to determine if racial disparities were present with respect to the use of prostate MRI. Compared with White men, Black, Asian, and Hispanic men were less likely to have a prostate MRI within 180 days after an elevated PSA (results stratified at 2.5, 4, or 10 ng/mL). The differences were most pronounced for patients with a PSA at 4 ng/mL or higher. The results suggest that providers should be aware of potential system and individual factors that influence racial and ethnic disparities in the use of prostate MRI.

            Studies designed to evaluate germline and somatic genomic abnormalities in prostate cancer have come to the forefront in the last decade. Lynch syndrome is an inherited cancer syndrome of abnormalities in at least one of the commonly recognized mismatch repair genes: MLH1, MSH2, MSH6, or PMS2. While testing for mismatch repair deficiency is recommended in the advanced setting where systemic therapy is being considered, such testing outside of known family history is unclear in the setting of screening for prostate cancer. Bancroft et al compared PSA levels (and prostate cancer incidence) as part of baseline screening between carriers of one of mismatch repair genes (MLH1, MSH2, MSH6) and non-carrier controls. Carriers of MLH1 and MSH6 variants had a higher incidence of prostate cancer compared with controls. While not yet recommended for standard practice, further studies will be needed to verify these compelling results.

            Racial and ethnic disparities in prostate cancer diagnosis and treatment are well recognized. Prostate magnetic resonance imaging (MRI) as part of a diagnostic approach for people with elevated PSA may decrease unnecessary biopsies or better direct biopsies based on results, and its use is increasing significantly. Abashidze et al examined Medicare claims between 2011 and 2017 to determine if racial disparities were present with respect to the use of prostate MRI. Compared with White men, Black, Asian, and Hispanic men were less likely to have a prostate MRI within 180 days after an elevated PSA (results stratified at 2.5, 4, or 10 ng/mL). The differences were most pronounced for patients with a PSA at 4 ng/mL or higher. The results suggest that providers should be aware of potential system and individual factors that influence racial and ethnic disparities in the use of prostate MRI.

            Studies designed to evaluate germline and somatic genomic abnormalities in prostate cancer have come to the forefront in the last decade. Lynch syndrome is an inherited cancer syndrome of abnormalities in at least one of the commonly recognized mismatch repair genes: MLH1, MSH2, MSH6, or PMS2. While testing for mismatch repair deficiency is recommended in the advanced setting where systemic therapy is being considered, such testing outside of known family history is unclear in the setting of screening for prostate cancer. Bancroft et al compared PSA levels (and prostate cancer incidence) as part of baseline screening between carriers of one of mismatch repair genes (MLH1, MSH2, MSH6) and non-carrier controls. Carriers of MLH1 and MSH6 variants had a higher incidence of prostate cancer compared with controls. While not yet recommended for standard practice, further studies will be needed to verify these compelling results.

            Racial and ethnic disparities in prostate cancer diagnosis and treatment are well recognized. Prostate magnetic resonance imaging (MRI) as part of a diagnostic approach for people with elevated PSA may decrease unnecessary biopsies or better direct biopsies based on results, and its use is increasing significantly. Abashidze et al examined Medicare claims between 2011 and 2017 to determine if racial disparities were present with respect to the use of prostate MRI. Compared with White men, Black, Asian, and Hispanic men were less likely to have a prostate MRI within 180 days after an elevated PSA (results stratified at 2.5, 4, or 10 ng/mL). The differences were most pronounced for patients with a PSA at 4 ng/mL or higher. The results suggest that providers should be aware of potential system and individual factors that influence racial and ethnic disparities in the use of prostate MRI.

            Studies designed to evaluate germline and somatic genomic abnormalities in prostate cancer have come to the forefront in the last decade. Lynch syndrome is an inherited cancer syndrome of abnormalities in at least one of the commonly recognized mismatch repair genes: MLH1, MSH2, MSH6, or PMS2. While testing for mismatch repair deficiency is recommended in the advanced setting where systemic therapy is being considered, such testing outside of known family history is unclear in the setting of screening for prostate cancer. Bancroft et al compared PSA levels (and prostate cancer incidence) as part of baseline screening between carriers of one of mismatch repair genes (MLH1, MSH2, MSH6) and non-carrier controls. Carriers of MLH1 and MSH6 variants had a higher incidence of prostate cancer compared with controls. While not yet recommended for standard practice, further studies will be needed to verify these compelling results.

In the study by Aggarwal et al., the investigators evaluated whether molecular subtypes as identified from biopsies of metastatic tumors in patients with metastatic castrate resistant prostate cancer (mCRPC) could result in improved prediction of response to therapies. In this retrospective study of 4 distinct cohorts, 45% of tumors were classified as luminal and 55% were classified as basal. Luminal tumors exhibited increased expression of androgen receptor pathway genes, and patients with luminal tumors had better survival after treatment with ASI compared with those with basal tumors. Genomic analyses of mCRPC metastases are challenging due to processing issues that can arise if bone decalcification needs to be done; therefore, this study provides an important next step to aid in the design appropriate clinical trials to investigate whether such genomic subtyping results in improved patient outcomes.

            In the study by Saad et al, the investigators evaluated whether the addition of the androgen receptor inhibitor apalutamide added to abiraterone would result in a higher radiographic progression free survival (rPFS) compared with abiraterone alone in patients with mCRPC. The combination resulted in an improvement in rPFS (24 versus 16.6 months); however, there was no improvement in overall survival. These results are similar to the Alliance A0321201 study, where enzalutamide was added to abiraterone, and no overall survival was observed. Further study is needed to determine if this combination strategy can work.

            Supportive care aside from ASIs or chemotherapy directed against prostate cancer is also of critical importance to patients with metastatic prostate cancer. Previous studies have demonstrated that BMAs, such as denosumab or zoledronic acid, result in the prevention of skeletal-related events (SREs) in patients with mCRPC. However, this same benefit has not been demonstrated in metastatic castrate sensitive prostate cancer (mCSPC); therefore, BMAs are not recommended in this population unless they are at high risk for osteoporotic fracture. Mitchell et al. evaluated a retrospective cohort identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine the number of patients with likely mCSPC treated with a BMA (defined as prescribed a BMA within 180 or 90 days after initial diagnosis of metastatic disease). A significant number of patients with likely mCSPC were prescribed BMAs within 180 days of diagnosis (23.6% of the cohort) and within 90 days (18.4% of the cohort). It is likely that most of these patients inappropriately received BMAs and were potentially subject to unnecessary costs and toxicity. Further study of strategies to reduce inappropriate BMA use could lead to less toxicity and lower costs.

In the study by Aggarwal et al., the investigators evaluated whether molecular subtypes as identified from biopsies of metastatic tumors in patients with metastatic castrate resistant prostate cancer (mCRPC) could result in improved prediction of response to therapies. In this retrospective study of 4 distinct cohorts, 45% of tumors were classified as luminal and 55% were classified as basal. Luminal tumors exhibited increased expression of androgen receptor pathway genes, and patients with luminal tumors had better survival after treatment with ASI compared with those with basal tumors. Genomic analyses of mCRPC metastases are challenging due to processing issues that can arise if bone decalcification needs to be done; therefore, this study provides an important next step to aid in the design appropriate clinical trials to investigate whether such genomic subtyping results in improved patient outcomes.

            In the study by Saad et al, the investigators evaluated whether the addition of the androgen receptor inhibitor apalutamide added to abiraterone would result in a higher radiographic progression free survival (rPFS) compared with abiraterone alone in patients with mCRPC. The combination resulted in an improvement in rPFS (24 versus 16.6 months); however, there was no improvement in overall survival. These results are similar to the Alliance A0321201 study, where enzalutamide was added to abiraterone, and no overall survival was observed. Further study is needed to determine if this combination strategy can work.

            Supportive care aside from ASIs or chemotherapy directed against prostate cancer is also of critical importance to patients with metastatic prostate cancer. Previous studies have demonstrated that BMAs, such as denosumab or zoledronic acid, result in the prevention of skeletal-related events (SREs) in patients with mCRPC. However, this same benefit has not been demonstrated in metastatic castrate sensitive prostate cancer (mCSPC); therefore, BMAs are not recommended in this population unless they are at high risk for osteoporotic fracture. Mitchell et al. evaluated a retrospective cohort identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine the number of patients with likely mCSPC treated with a BMA (defined as prescribed a BMA within 180 or 90 days after initial diagnosis of metastatic disease). A significant number of patients with likely mCSPC were prescribed BMAs within 180 days of diagnosis (23.6% of the cohort) and within 90 days (18.4% of the cohort). It is likely that most of these patients inappropriately received BMAs and were potentially subject to unnecessary costs and toxicity. Further study of strategies to reduce inappropriate BMA use could lead to less toxicity and lower costs.

In the study by Aggarwal et al., the investigators evaluated whether molecular subtypes as identified from biopsies of metastatic tumors in patients with metastatic castrate resistant prostate cancer (mCRPC) could result in improved prediction of response to therapies. In this retrospective study of 4 distinct cohorts, 45% of tumors were classified as luminal and 55% were classified as basal. Luminal tumors exhibited increased expression of androgen receptor pathway genes, and patients with luminal tumors had better survival after treatment with ASI compared with those with basal tumors. Genomic analyses of mCRPC metastases are challenging due to processing issues that can arise if bone decalcification needs to be done; therefore, this study provides an important next step to aid in the design appropriate clinical trials to investigate whether such genomic subtyping results in improved patient outcomes.

            In the study by Saad et al, the investigators evaluated whether the addition of the androgen receptor inhibitor apalutamide added to abiraterone would result in a higher radiographic progression free survival (rPFS) compared with abiraterone alone in patients with mCRPC. The combination resulted in an improvement in rPFS (24 versus 16.6 months); however, there was no improvement in overall survival. These results are similar to the Alliance A0321201 study, where enzalutamide was added to abiraterone, and no overall survival was observed. Further study is needed to determine if this combination strategy can work.

            Supportive care aside from ASIs or chemotherapy directed against prostate cancer is also of critical importance to patients with metastatic prostate cancer. Previous studies have demonstrated that BMAs, such as denosumab or zoledronic acid, result in the prevention of skeletal-related events (SREs) in patients with mCRPC. However, this same benefit has not been demonstrated in metastatic castrate sensitive prostate cancer (mCSPC); therefore, BMAs are not recommended in this population unless they are at high risk for osteoporotic fracture. Mitchell et al. evaluated a retrospective cohort identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine the number of patients with likely mCSPC treated with a BMA (defined as prescribed a BMA within 180 or 90 days after initial diagnosis of metastatic disease). A significant number of patients with likely mCSPC were prescribed BMAs within 180 days of diagnosis (23.6% of the cohort) and within 90 days (18.4% of the cohort). It is likely that most of these patients inappropriately received BMAs and were potentially subject to unnecessary costs and toxicity. Further study of strategies to reduce inappropriate BMA use could lead to less toxicity and lower costs.

            Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.

            Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.

            Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.

            Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.

            The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.

            Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.

            Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.

            Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.

            Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.

            The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.

            Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.

            Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.

            Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.

            Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.

            The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.

In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.

In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies

Varying strategies have been evaluated to diagnose and predict risk of prostate cancer more optimally. The presence of local or systemic inflammation has been postulated to be associated with increased risk of the presence and aggressiveness of prostate cancer. Complete blood counts with differential white counts are routinely obtained, and the ratio of platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and monocytes to lymphocytes (MLR) have been proposed as markers of inflammation. In the study by Lee et al., the authors evaluated whether the PLR was associated with benign prostate disease, clinically insignificant prostate cancer (Gleason 6 or lower), or clinically significant prostate cancer (Gleason 7 or higher) in patients undergoing prostate biopsy. In a cohort of 1652 who underwent biopsy, the only significant finding was a lower PLR in patients with clinically significant prostate cancer and a PSA < 10 ng/mL compared with patients having benign disease or clinically insignificant disease.

Rundle et al evaluated whether NLR or MLR in the setting of cancer varied by race, as African American and Black men are at higher risk for prostate cancer than White men. In this case-control study that included 822 cases of prostate cancer and 573 controls, there were no significant differences in the trajectories of NLR or MLR over time between cases or controls in the entire cohort. The NLR and MLR were higher over time for White men without prostate cancer compared with White men with prostate cancer; however, no such difference was identified when comparing Black men with or without prostate cancer. Thus, while there may be some association between inflammation and prostate cancer diagnoses or risk of aggressiveness, the use of PLR, NLR, or MLR requires much more study to fully determine the usefulness of these ratios.

A slightly different approach to improve diagnostic strategies has been to utilize prostate MRI to identify areas of the prostate suggestive of cancer. Eklund et al evaluated the use of MRI in the setting of an organized prostate screening program. The use of MRI with targeted and standard biopsy was noninferior to standard biopsy alone in detecting clinically significant prostate cancer while fewer clinically insignificant prostate cancers were identified in the MRI with targeted and standard biopsy group compared with the standard biopsy group. This study further supports the increasing utilization of MRI as part of a biopsy approach in men at risk for prostate cancer.

Varying strategies have been evaluated to diagnose and predict risk of prostate cancer more optimally. The presence of local or systemic inflammation has been postulated to be associated with increased risk of the presence and aggressiveness of prostate cancer. Complete blood counts with differential white counts are routinely obtained, and the ratio of platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and monocytes to lymphocytes (MLR) have been proposed as markers of inflammation. In the study by Lee et al., the authors evaluated whether the PLR was associated with benign prostate disease, clinically insignificant prostate cancer (Gleason 6 or lower), or clinically significant prostate cancer (Gleason 7 or higher) in patients undergoing prostate biopsy. In a cohort of 1652 who underwent biopsy, the only significant finding was a lower PLR in patients with clinically significant prostate cancer and a PSA < 10 ng/mL compared with patients having benign disease or clinically insignificant disease.

Rundle et al evaluated whether NLR or MLR in the setting of cancer varied by race, as African American and Black men are at higher risk for prostate cancer than White men. In this case-control study that included 822 cases of prostate cancer and 573 controls, there were no significant differences in the trajectories of NLR or MLR over time between cases or controls in the entire cohort. The NLR and MLR were higher over time for White men without prostate cancer compared with White men with prostate cancer; however, no such difference was identified when comparing Black men with or without prostate cancer. Thus, while there may be some association between inflammation and prostate cancer diagnoses or risk of aggressiveness, the use of PLR, NLR, or MLR requires much more study to fully determine the usefulness of these ratios.

A slightly different approach to improve diagnostic strategies has been to utilize prostate MRI to identify areas of the prostate suggestive of cancer. Eklund et al evaluated the use of MRI in the setting of an organized prostate screening program. The use of MRI with targeted and standard biopsy was noninferior to standard biopsy alone in detecting clinically significant prostate cancer while fewer clinically insignificant prostate cancers were identified in the MRI with targeted and standard biopsy group compared with the standard biopsy group. This study further supports the increasing utilization of MRI as part of a biopsy approach in men at risk for prostate cancer.

Varying strategies have been evaluated to diagnose and predict risk of prostate cancer more optimally. The presence of local or systemic inflammation has been postulated to be associated with increased risk of the presence and aggressiveness of prostate cancer. Complete blood counts with differential white counts are routinely obtained, and the ratio of platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and monocytes to lymphocytes (MLR) have been proposed as markers of inflammation. In the study by Lee et al., the authors evaluated whether the PLR was associated with benign prostate disease, clinically insignificant prostate cancer (Gleason 6 or lower), or clinically significant prostate cancer (Gleason 7 or higher) in patients undergoing prostate biopsy. In a cohort of 1652 who underwent biopsy, the only significant finding was a lower PLR in patients with clinically significant prostate cancer and a PSA < 10 ng/mL compared with patients having benign disease or clinically insignificant disease.

Rundle et al evaluated whether NLR or MLR in the setting of cancer varied by race, as African American and Black men are at higher risk for prostate cancer than White men. In this case-control study that included 822 cases of prostate cancer and 573 controls, there were no significant differences in the trajectories of NLR or MLR over time between cases or controls in the entire cohort. The NLR and MLR were higher over time for White men without prostate cancer compared with White men with prostate cancer; however, no such difference was identified when comparing Black men with or without prostate cancer. Thus, while there may be some association between inflammation and prostate cancer diagnoses or risk of aggressiveness, the use of PLR, NLR, or MLR requires much more study to fully determine the usefulness of these ratios.

A slightly different approach to improve diagnostic strategies has been to utilize prostate MRI to identify areas of the prostate suggestive of cancer. Eklund et al evaluated the use of MRI in the setting of an organized prostate screening program. The use of MRI with targeted and standard biopsy was noninferior to standard biopsy alone in detecting clinically significant prostate cancer while fewer clinically insignificant prostate cancers were identified in the MRI with targeted and standard biopsy group compared with the standard biopsy group. This study further supports the increasing utilization of MRI as part of a biopsy approach in men at risk for prostate cancer.

Treatment of prostate cancer presents significant challenges with respect to balancing efficacy and side effects of treatments. Thus, quality of life endpoints are included in studies of patients with prostate cancer to better understand and counsel patients with this heterogenous disease. In the 3 studies discussed here, functional or quality of life outcomes were included in the analyses.

            In the first study, Hagens et al evaluated the effects of postoperative complications of robot-assisted radical prostatectomy on the health-related quality of life (HRQoL) as measured via surveys and assessment of functional outcomes. While no significant association between HRQoL at 6 months and complications postoperatively were identified, there was an association between functional outcomes and HRQoL at 6 months identified. Thus, future studies designed to identify more optimal patient selection or improved surgical techniques may benefit patients.

            Studies have suggested that androgen deprivation therapy (ADT) may be associated with decreased cognitive function. However, other studies suggested that ADT via luteinizing hormone releasing hormone (LHRH) agonists or antagonists may actually have a protective effect against decreased cognitive function due to low gonadotropin exposure. Andela et al conducted a systematic review based on this hypothesis. Of the 31 studies included in the review, 16 demonstrated that ADT was not associated with decreased cognitive function, while 11 studies did support this association and 4 studies were inconclusive. Therefore, no definitive conclusions can be made based on this review, and further randomized studies are needed.

            Radiation to the prostate may affect the rectum with sometimes significant effects. Hydrogel spacers injected between the prostate and rectum have been evaluated in patients with conventional radiation previously with evidence of benefit, but the benefits for patients undergoing stereotactic body radiotherapy (SBRT) are unknown. Ogita et al conducted a phase II single-arm study designed to evaluate the effects of a hydrogel spacer on gastrointestinal toxicity within 3 months of SBRT. Physician-assessed toxicity was not reduced, but patient reported toxicity was improved compared with historical controls. While this study does not support routine use in the setting of prostate SBRT, it does suggest that future larger randomized studies are worth consideration.

Treatment of prostate cancer presents significant challenges with respect to balancing efficacy and side effects of treatments. Thus, quality of life endpoints are included in studies of patients with prostate cancer to better understand and counsel patients with this heterogenous disease. In the 3 studies discussed here, functional or quality of life outcomes were included in the analyses.

            In the first study, Hagens et al evaluated the effects of postoperative complications of robot-assisted radical prostatectomy on the health-related quality of life (HRQoL) as measured via surveys and assessment of functional outcomes. While no significant association between HRQoL at 6 months and complications postoperatively were identified, there was an association between functional outcomes and HRQoL at 6 months identified. Thus, future studies designed to identify more optimal patient selection or improved surgical techniques may benefit patients.

            Studies have suggested that androgen deprivation therapy (ADT) may be associated with decreased cognitive function. However, other studies suggested that ADT via luteinizing hormone releasing hormone (LHRH) agonists or antagonists may actually have a protective effect against decreased cognitive function due to low gonadotropin exposure. Andela et al conducted a systematic review based on this hypothesis. Of the 31 studies included in the review, 16 demonstrated that ADT was not associated with decreased cognitive function, while 11 studies did support this association and 4 studies were inconclusive. Therefore, no definitive conclusions can be made based on this review, and further randomized studies are needed.

            Radiation to the prostate may affect the rectum with sometimes significant effects. Hydrogel spacers injected between the prostate and rectum have been evaluated in patients with conventional radiation previously with evidence of benefit, but the benefits for patients undergoing stereotactic body radiotherapy (SBRT) are unknown. Ogita et al conducted a phase II single-arm study designed to evaluate the effects of a hydrogel spacer on gastrointestinal toxicity within 3 months of SBRT. Physician-assessed toxicity was not reduced, but patient reported toxicity was improved compared with historical controls. While this study does not support routine use in the setting of prostate SBRT, it does suggest that future larger randomized studies are worth consideration.

Treatment of prostate cancer presents significant challenges with respect to balancing efficacy and side effects of treatments. Thus, quality of life endpoints are included in studies of patients with prostate cancer to better understand and counsel patients with this heterogenous disease. In the 3 studies discussed here, functional or quality of life outcomes were included in the analyses.

            In the first study, Hagens et al evaluated the effects of postoperative complications of robot-assisted radical prostatectomy on the health-related quality of life (HRQoL) as measured via surveys and assessment of functional outcomes. While no significant association between HRQoL at 6 months and complications postoperatively were identified, there was an association between functional outcomes and HRQoL at 6 months identified. Thus, future studies designed to identify more optimal patient selection or improved surgical techniques may benefit patients.

            Studies have suggested that androgen deprivation therapy (ADT) may be associated with decreased cognitive function. However, other studies suggested that ADT via luteinizing hormone releasing hormone (LHRH) agonists or antagonists may actually have a protective effect against decreased cognitive function due to low gonadotropin exposure. Andela et al conducted a systematic review based on this hypothesis. Of the 31 studies included in the review, 16 demonstrated that ADT was not associated with decreased cognitive function, while 11 studies did support this association and 4 studies were inconclusive. Therefore, no definitive conclusions can be made based on this review, and further randomized studies are needed.

            Radiation to the prostate may affect the rectum with sometimes significant effects. Hydrogel spacers injected between the prostate and rectum have been evaluated in patients with conventional radiation previously with evidence of benefit, but the benefits for patients undergoing stereotactic body radiotherapy (SBRT) are unknown. Ogita et al conducted a phase II single-arm study designed to evaluate the effects of a hydrogel spacer on gastrointestinal toxicity within 3 months of SBRT. Physician-assessed toxicity was not reduced, but patient reported toxicity was improved compared with historical controls. While this study does not support routine use in the setting of prostate SBRT, it does suggest that future larger randomized studies are worth consideration.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.