Hepatocellular Carcinoma

Key clinical point: After a median of 27 months’ follow-up, the rates of conversion therapy and both overall and progression-free survival were significantly higher in HCC patients treated with pembrolizumab-lenvatinib-TACE compared to those treated with lenvatinib-TACE.

Major finding: The rate of conversion therapy at the last follow-up was 25.7% in the pembrolizumab-lenvatinib-TACE group vs 11.1% in the lenvatinib-TACE group; median overall survival was 18.1 months in the pembrolizumab-lenvatinib-TACE group vs 14.1 months in the lenvatinib-TACE group, and median progression-free survival interval was 9.2 months in the pembrolizumab-lenvatinib-TACE group vs 5.5 months in the lenvatinib-TACE group.

Study details: The data come from a retrospective study of 142 consecutive adult patients with programmed cell death ligand-1 (PD-L1)-positive unresectable hepatocellular carcinoma who were treated with either pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) or lenvatinib-TACE sequential therapy.

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

Source: Chen S et al. J Cancer Res Clin Oncol. 2021 Aug 28. doi: 10.1007/s00432-021-03767-4.

Key clinical point: After a median of 27 months’ follow-up, the rates of conversion therapy and both overall and progression-free survival were significantly higher in HCC patients treated with pembrolizumab-lenvatinib-TACE compared to those treated with lenvatinib-TACE.

Major finding: The rate of conversion therapy at the last follow-up was 25.7% in the pembrolizumab-lenvatinib-TACE group vs 11.1% in the lenvatinib-TACE group; median overall survival was 18.1 months in the pembrolizumab-lenvatinib-TACE group vs 14.1 months in the lenvatinib-TACE group, and median progression-free survival interval was 9.2 months in the pembrolizumab-lenvatinib-TACE group vs 5.5 months in the lenvatinib-TACE group.

Study details: The data come from a retrospective study of 142 consecutive adult patients with programmed cell death ligand-1 (PD-L1)-positive unresectable hepatocellular carcinoma who were treated with either pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) or lenvatinib-TACE sequential therapy.

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

Source: Chen S et al. J Cancer Res Clin Oncol. 2021 Aug 28. doi: 10.1007/s00432-021-03767-4.

Key clinical point: After a median of 27 months’ follow-up, the rates of conversion therapy and both overall and progression-free survival were significantly higher in HCC patients treated with pembrolizumab-lenvatinib-TACE compared to those treated with lenvatinib-TACE.

Major finding: The rate of conversion therapy at the last follow-up was 25.7% in the pembrolizumab-lenvatinib-TACE group vs 11.1% in the lenvatinib-TACE group; median overall survival was 18.1 months in the pembrolizumab-lenvatinib-TACE group vs 14.1 months in the lenvatinib-TACE group, and median progression-free survival interval was 9.2 months in the pembrolizumab-lenvatinib-TACE group vs 5.5 months in the lenvatinib-TACE group.

Study details: The data come from a retrospective study of 142 consecutive adult patients with programmed cell death ligand-1 (PD-L1)-positive unresectable hepatocellular carcinoma who were treated with either pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) or lenvatinib-TACE sequential therapy.

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

Source: Chen S et al. J Cancer Res Clin Oncol. 2021 Aug 28. doi: 10.1007/s00432-021-03767-4.

Hepatocellular cancer (HCC) is the most common type of hepatic cancers, accounting for 65% of all hepatic cancers.¹ Among all cancers, HCC is one of the fastest growing causes of death in the United States, and the rate of new HCC cases are on the rise over several decades.² There are many risk factors leading to HCC, including alcohol use, obesity, and smoking. Infection with hepatitis C virus (HCV) poses a significant risk.¹

The pathogenesis of HCV-induced carcinogenesis is mediated by a unique host-induced immunologic response. Viral replication induces production of inflammatory factors, such as tumor necrosis factor (TNF-α), interferon (IFN), and oxidative stress on hepatocytes, resulting in cell injury, death, and regeneration. Repetitive cycles of cellular death and regeneration induce fibrosis, which may lead to cirrhosis.³ Hence, early treatment of HCV infection and achieving sustained virologic response (SVR) may lead to decreased incidence and mortality associated with HCC.

Treatment of HCV infection has become more effective with the development of direct-acting antivirals (DAAs) leading to SVR in > 90% of patients compared with 40 to 50% with IFN-based treatment.^4,5 DAAs have been proved safe and highly effective in eradicating HCV infection even in patients with advanced liver disease with decompensated cirrhosis.⁶ Although achieving SVR indicates a complete cure from chronic HCV infection, several studies have shown subsequent risk of developing HCC persists even after successful HCV treatment.^7-9 Some studies show that using DAAs to achieve SVR in patients with HCV infection leads to a decreased relative risk of HCC development compared with patients who do not receive treatment.^10-12 But data on HCC risk following DAA-induced SVR vs IFN-induced SVR are somewhat conflicting.

Much of the information regarding the association between SVR and HCC has been gleaned from large data banks without accounting for individual patient characteristics that can be obtained through full chart review. Due to small sample sizes in many chart review studies, the impact that SVR from DAA therapy has on the progression and severity of HCC is not entirely clear. The aim of our study is to evaluate the effect of HCV treatment and SVR status on overall survival (OS) in patients with HCC. Second, we aim to compare survival benefits, if any exist, among the 2 major HCV treatment modalities (IFN vs DAA).

Methods

We performed a retrospective review of patients at Memphis Veterans Affairs Medical Center (VAMC) in Tennessee to determine whether treatment for HCV infection in general, and achieving SVR in particular, makes a difference in progression, recurrence, or OS among patients with HCV infection who develop HCC. We identified 111 patients with a diagnosis of both HCV and new or recurrent HCC lesions from November 2008 to March 2019 (Table 1). We divided these patients based on their HCV treatment status, SVR status, and treatment types (IFN vs DAA).

The inclusion criteria were patients aged > 18 years treated at the Memphis VAMC who have HCV infection and developed HCC. Exclusion criteria were patients who developed HCC from other causes such as alcoholic steatohepatitis, hepatitis B virus infection, hemochromatosis, patients without HCV infection, and patients who were not established at the Memphis VAMC. This protocol was approved by the Memphis VAMC Institutional Review Board.

Statistical Analysis

OS was measured from the date of HCC diagnosis to the date of death or last follow-up. Progression-free survival (PFS) was defined from the date of HCC treatment initiation to the date of first HCC recurrence. We compared survival data for the SVR and non-SVR subgroups, the HCV treatment vs non-HCV treatment subgroups, and the IFN therapy vs DAA therapy subgroups, using the Kaplan-Meier method. The differences between subgroups were assessed using a log-rank test. Multivariate analysis using Cox proportional hazards regression model was used to identify factors that had significant impact on OS. Those factors included age; race; alcohol, tobacco, and illicit drug use; SVR status; HCV treatment status; IFN-based regimen vs DAA; MELD, and Child-Pugh scores. The results were expressed as hazard ratios (HRs) and 95% CI. Calculations were made using Statistical Analysis SAS and IBM SPSS software.

Results

The study included 111 patients. The mean age was 65.7 years; all were male and half of were Black patients. The gender imbalance was due to the predominantly male patient population at Memphis VAMC. Among 111 patients with HCV infection and HCC, 68 patients were treated for HCV infection and had significantly improved OS and PFS compared with the nontreatment group. The median 5-year OS was 44.6 months (95% CI, 966-3202) in the treated HCV infection group compared with 15.1 months in the untreated HCV infection group with a Wilcoxon P = .0005 (Figure 1). Similarly, patients treated for HCV infection had a significantly better 5-year PFS of 15.3 months (95% CI, 294-726) compared with the nontreatment group 9.5 months (95% CI, 205-405) with a Wilcoxon P = .04 (Figure 2).

Among 68 patients treated for HCV infection, 51 achieved SVR, and 34 achieved SVR after the diagnosis of HCC. Patients who achieved SVR had an improved 5-year OS when compared with patients who did not achieve SVR (median 65.8 months [95% CI, 1222-NA] vs 15.7 months [95% CI, 242-853], Wilcoxon P < .001) (Figure 3). Similarly, patients with SVR had improved 5-year PFS when compared with the non-SVR group (median 20.5 months [95% CI, 431-914] vs 8.9 months [95% CI, 191-340], Wilcoxon P = .007 (Figure 4). Achievement of SVR after HCC diagnosis suggests a significantly improved OS (HR 0.37) compared with achievement prior to HCC diagnosis (HR, 0.65; 95% CI, 0.23-1.82, P = .41)

Discussion

The survival benefit of HCV eradication and achieving SVR status has been well established in patients with HCC.¹³ In a retrospective cohort study of 250 patients with HCV infection who had received curative treatment for HCC, multivariate analysis demonstrated that achieving SVR is an independent predictor of OS.¹⁴ The 3-year and 5-year OS rates were 97% and 94% for the SVR group, and 91% and 60% for the non‐SVR group, respectively (P < .001). Similarly, according to Sou and colleagues, of 122 patients with HCV-related HCC, patients with SVR had longer OS than patients with no SVR (P = .04).¹⁵ One of the hypotheses that could explain the survival benefit in patients who achieved SVR is the effect of achieving SVR in reducing persistent liver inflammation and associated liver mortality, and therefore lowering risks of complication in patients with HCC.¹⁶ In our study, multivariate analysis shows that achieving SVR is associated with significant improved OS (HR, 0.33). In contrast, patients with HCC who have not achieved SVR are associated with worse survival (HR, 3.24). This finding supports early treatment of HCV to obtain SVR in HCV-related patients with HCC, even after development of HCC.

Among 68 patients treated for HCV infection, 45 patients were treated after HCC diagnosis, and 34 patients achieved SVR after HCC diagnosis. The average time between HCV infection treatment after HCC diagnosis was 6 months. Our data suggested that achievement of SVR after HCC diagnosis suggests an improved OS (HR, 0.37) compared with achievement prior to HCC diagnosis (HR, 0.65; 95% CI,0.23-1.82; P = .41). This lack of statistical significance is likely due to small sample size of patients achieving SVR prior to HCC diagnosis. Our results are consistent with the findings regarding the efficacy and timing of DAA treatment in patients with active HCC. According to Singal and colleagues, achieving SVR after DAA therapy may result in improved liver function and facilitate additional HCC-directed therapy, which potentially improves survival.^17-19

Nagaoki and colleagues found that there was no significant difference in OS in patients with HCC between the DAA and IFN groups. According to the study, the 3-year and 5-year OS rates were 96% and 96% for DAA patients and 93% and 73% for IFN patients, respectively (P = .16).¹⁴ This finding is consistent with the results of our study. HCV treatment type (IFN vs DAA) was not found to be associated with either OS or PFS time, regardless of time period.

Limitations

Our findings were limited in that our study population is too small to conduct further subset analysis that would allow statistical significance of those subsets, such as the suggested benefit of SVR in patients who presented with HCC after antiviral therapy. Another limitation is the all-male population, likely a result of the older veteran population at the Memphis VAMC. The mean age at diagnosis was 65 years, which is slightly higher than the general population. Compared to the SEER database, HCC is most frequently diagnosed among people aged 55 to 64 years.²³ The age difference was likely due to our aging veteran population.

Further studies are needed to determine the significance of SVR on HCC recurrence and treatment. Immunotherapy is now first-line treatment for patients with local advanced HCC. All the immunotherapy studies excluded patients with active HCV infection. Hence, we need more data on HCV treatment timing among patients scheduled to start treatment with immunotherapy.

Conclusions

In a population of older veterans, treatment of HCV infection leads to OS benefit among patients with HCC. In addition, patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs IFN-based regimen, did not show significant survival benefit.

Hepatocellular cancer (HCC) is the most common type of hepatic cancers, accounting for 65% of all hepatic cancers.¹ Among all cancers, HCC is one of the fastest growing causes of death in the United States, and the rate of new HCC cases are on the rise over several decades.² There are many risk factors leading to HCC, including alcohol use, obesity, and smoking. Infection with hepatitis C virus (HCV) poses a significant risk.¹

The pathogenesis of HCV-induced carcinogenesis is mediated by a unique host-induced immunologic response. Viral replication induces production of inflammatory factors, such as tumor necrosis factor (TNF-α), interferon (IFN), and oxidative stress on hepatocytes, resulting in cell injury, death, and regeneration. Repetitive cycles of cellular death and regeneration induce fibrosis, which may lead to cirrhosis.³ Hence, early treatment of HCV infection and achieving sustained virologic response (SVR) may lead to decreased incidence and mortality associated with HCC.

Treatment of HCV infection has become more effective with the development of direct-acting antivirals (DAAs) leading to SVR in > 90% of patients compared with 40 to 50% with IFN-based treatment.^4,5 DAAs have been proved safe and highly effective in eradicating HCV infection even in patients with advanced liver disease with decompensated cirrhosis.⁶ Although achieving SVR indicates a complete cure from chronic HCV infection, several studies have shown subsequent risk of developing HCC persists even after successful HCV treatment.^7-9 Some studies show that using DAAs to achieve SVR in patients with HCV infection leads to a decreased relative risk of HCC development compared with patients who do not receive treatment.^10-12 But data on HCC risk following DAA-induced SVR vs IFN-induced SVR are somewhat conflicting.

Much of the information regarding the association between SVR and HCC has been gleaned from large data banks without accounting for individual patient characteristics that can be obtained through full chart review. Due to small sample sizes in many chart review studies, the impact that SVR from DAA therapy has on the progression and severity of HCC is not entirely clear. The aim of our study is to evaluate the effect of HCV treatment and SVR status on overall survival (OS) in patients with HCC. Second, we aim to compare survival benefits, if any exist, among the 2 major HCV treatment modalities (IFN vs DAA).

Methods

We performed a retrospective review of patients at Memphis Veterans Affairs Medical Center (VAMC) in Tennessee to determine whether treatment for HCV infection in general, and achieving SVR in particular, makes a difference in progression, recurrence, or OS among patients with HCV infection who develop HCC. We identified 111 patients with a diagnosis of both HCV and new or recurrent HCC lesions from November 2008 to March 2019 (Table 1). We divided these patients based on their HCV treatment status, SVR status, and treatment types (IFN vs DAA).

The inclusion criteria were patients aged > 18 years treated at the Memphis VAMC who have HCV infection and developed HCC. Exclusion criteria were patients who developed HCC from other causes such as alcoholic steatohepatitis, hepatitis B virus infection, hemochromatosis, patients without HCV infection, and patients who were not established at the Memphis VAMC. This protocol was approved by the Memphis VAMC Institutional Review Board.

Statistical Analysis

OS was measured from the date of HCC diagnosis to the date of death or last follow-up. Progression-free survival (PFS) was defined from the date of HCC treatment initiation to the date of first HCC recurrence. We compared survival data for the SVR and non-SVR subgroups, the HCV treatment vs non-HCV treatment subgroups, and the IFN therapy vs DAA therapy subgroups, using the Kaplan-Meier method. The differences between subgroups were assessed using a log-rank test. Multivariate analysis using Cox proportional hazards regression model was used to identify factors that had significant impact on OS. Those factors included age; race; alcohol, tobacco, and illicit drug use; SVR status; HCV treatment status; IFN-based regimen vs DAA; MELD, and Child-Pugh scores. The results were expressed as hazard ratios (HRs) and 95% CI. Calculations were made using Statistical Analysis SAS and IBM SPSS software.

Results

The study included 111 patients. The mean age was 65.7 years; all were male and half of were Black patients. The gender imbalance was due to the predominantly male patient population at Memphis VAMC. Among 111 patients with HCV infection and HCC, 68 patients were treated for HCV infection and had significantly improved OS and PFS compared with the nontreatment group. The median 5-year OS was 44.6 months (95% CI, 966-3202) in the treated HCV infection group compared with 15.1 months in the untreated HCV infection group with a Wilcoxon P = .0005 (Figure 1). Similarly, patients treated for HCV infection had a significantly better 5-year PFS of 15.3 months (95% CI, 294-726) compared with the nontreatment group 9.5 months (95% CI, 205-405) with a Wilcoxon P = .04 (Figure 2).

Among 68 patients treated for HCV infection, 51 achieved SVR, and 34 achieved SVR after the diagnosis of HCC. Patients who achieved SVR had an improved 5-year OS when compared with patients who did not achieve SVR (median 65.8 months [95% CI, 1222-NA] vs 15.7 months [95% CI, 242-853], Wilcoxon P < .001) (Figure 3). Similarly, patients with SVR had improved 5-year PFS when compared with the non-SVR group (median 20.5 months [95% CI, 431-914] vs 8.9 months [95% CI, 191-340], Wilcoxon P = .007 (Figure 4). Achievement of SVR after HCC diagnosis suggests a significantly improved OS (HR 0.37) compared with achievement prior to HCC diagnosis (HR, 0.65; 95% CI, 0.23-1.82, P = .41)

Discussion

The survival benefit of HCV eradication and achieving SVR status has been well established in patients with HCC.¹³ In a retrospective cohort study of 250 patients with HCV infection who had received curative treatment for HCC, multivariate analysis demonstrated that achieving SVR is an independent predictor of OS.¹⁴ The 3-year and 5-year OS rates were 97% and 94% for the SVR group, and 91% and 60% for the non‐SVR group, respectively (P < .001). Similarly, according to Sou and colleagues, of 122 patients with HCV-related HCC, patients with SVR had longer OS than patients with no SVR (P = .04).¹⁵ One of the hypotheses that could explain the survival benefit in patients who achieved SVR is the effect of achieving SVR in reducing persistent liver inflammation and associated liver mortality, and therefore lowering risks of complication in patients with HCC.¹⁶ In our study, multivariate analysis shows that achieving SVR is associated with significant improved OS (HR, 0.33). In contrast, patients with HCC who have not achieved SVR are associated with worse survival (HR, 3.24). This finding supports early treatment of HCV to obtain SVR in HCV-related patients with HCC, even after development of HCC.

Among 68 patients treated for HCV infection, 45 patients were treated after HCC diagnosis, and 34 patients achieved SVR after HCC diagnosis. The average time between HCV infection treatment after HCC diagnosis was 6 months. Our data suggested that achievement of SVR after HCC diagnosis suggests an improved OS (HR, 0.37) compared with achievement prior to HCC diagnosis (HR, 0.65; 95% CI,0.23-1.82; P = .41). This lack of statistical significance is likely due to small sample size of patients achieving SVR prior to HCC diagnosis. Our results are consistent with the findings regarding the efficacy and timing of DAA treatment in patients with active HCC. According to Singal and colleagues, achieving SVR after DAA therapy may result in improved liver function and facilitate additional HCC-directed therapy, which potentially improves survival.^17-19

Nagaoki and colleagues found that there was no significant difference in OS in patients with HCC between the DAA and IFN groups. According to the study, the 3-year and 5-year OS rates were 96% and 96% for DAA patients and 93% and 73% for IFN patients, respectively (P = .16).¹⁴ This finding is consistent with the results of our study. HCV treatment type (IFN vs DAA) was not found to be associated with either OS or PFS time, regardless of time period.

Limitations

Our findings were limited in that our study population is too small to conduct further subset analysis that would allow statistical significance of those subsets, such as the suggested benefit of SVR in patients who presented with HCC after antiviral therapy. Another limitation is the all-male population, likely a result of the older veteran population at the Memphis VAMC. The mean age at diagnosis was 65 years, which is slightly higher than the general population. Compared to the SEER database, HCC is most frequently diagnosed among people aged 55 to 64 years.²³ The age difference was likely due to our aging veteran population.

Further studies are needed to determine the significance of SVR on HCC recurrence and treatment. Immunotherapy is now first-line treatment for patients with local advanced HCC. All the immunotherapy studies excluded patients with active HCV infection. Hence, we need more data on HCV treatment timing among patients scheduled to start treatment with immunotherapy.

Conclusions

In a population of older veterans, treatment of HCV infection leads to OS benefit among patients with HCC. In addition, patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs IFN-based regimen, did not show significant survival benefit.

Hepatocellular cancer (HCC) is the most common type of hepatic cancers, accounting for 65% of all hepatic cancers.¹ Among all cancers, HCC is one of the fastest growing causes of death in the United States, and the rate of new HCC cases are on the rise over several decades.² There are many risk factors leading to HCC, including alcohol use, obesity, and smoking. Infection with hepatitis C virus (HCV) poses a significant risk.¹

The pathogenesis of HCV-induced carcinogenesis is mediated by a unique host-induced immunologic response. Viral replication induces production of inflammatory factors, such as tumor necrosis factor (TNF-α), interferon (IFN), and oxidative stress on hepatocytes, resulting in cell injury, death, and regeneration. Repetitive cycles of cellular death and regeneration induce fibrosis, which may lead to cirrhosis.³ Hence, early treatment of HCV infection and achieving sustained virologic response (SVR) may lead to decreased incidence and mortality associated with HCC.

Treatment of HCV infection has become more effective with the development of direct-acting antivirals (DAAs) leading to SVR in > 90% of patients compared with 40 to 50% with IFN-based treatment.^4,5 DAAs have been proved safe and highly effective in eradicating HCV infection even in patients with advanced liver disease with decompensated cirrhosis.⁶ Although achieving SVR indicates a complete cure from chronic HCV infection, several studies have shown subsequent risk of developing HCC persists even after successful HCV treatment.^7-9 Some studies show that using DAAs to achieve SVR in patients with HCV infection leads to a decreased relative risk of HCC development compared with patients who do not receive treatment.^10-12 But data on HCC risk following DAA-induced SVR vs IFN-induced SVR are somewhat conflicting.

Much of the information regarding the association between SVR and HCC has been gleaned from large data banks without accounting for individual patient characteristics that can be obtained through full chart review. Due to small sample sizes in many chart review studies, the impact that SVR from DAA therapy has on the progression and severity of HCC is not entirely clear. The aim of our study is to evaluate the effect of HCV treatment and SVR status on overall survival (OS) in patients with HCC. Second, we aim to compare survival benefits, if any exist, among the 2 major HCV treatment modalities (IFN vs DAA).

Methods

We performed a retrospective review of patients at Memphis Veterans Affairs Medical Center (VAMC) in Tennessee to determine whether treatment for HCV infection in general, and achieving SVR in particular, makes a difference in progression, recurrence, or OS among patients with HCV infection who develop HCC. We identified 111 patients with a diagnosis of both HCV and new or recurrent HCC lesions from November 2008 to March 2019 (Table 1). We divided these patients based on their HCV treatment status, SVR status, and treatment types (IFN vs DAA).

The inclusion criteria were patients aged > 18 years treated at the Memphis VAMC who have HCV infection and developed HCC. Exclusion criteria were patients who developed HCC from other causes such as alcoholic steatohepatitis, hepatitis B virus infection, hemochromatosis, patients without HCV infection, and patients who were not established at the Memphis VAMC. This protocol was approved by the Memphis VAMC Institutional Review Board.

Statistical Analysis

OS was measured from the date of HCC diagnosis to the date of death or last follow-up. Progression-free survival (PFS) was defined from the date of HCC treatment initiation to the date of first HCC recurrence. We compared survival data for the SVR and non-SVR subgroups, the HCV treatment vs non-HCV treatment subgroups, and the IFN therapy vs DAA therapy subgroups, using the Kaplan-Meier method. The differences between subgroups were assessed using a log-rank test. Multivariate analysis using Cox proportional hazards regression model was used to identify factors that had significant impact on OS. Those factors included age; race; alcohol, tobacco, and illicit drug use; SVR status; HCV treatment status; IFN-based regimen vs DAA; MELD, and Child-Pugh scores. The results were expressed as hazard ratios (HRs) and 95% CI. Calculations were made using Statistical Analysis SAS and IBM SPSS software.

Results

The study included 111 patients. The mean age was 65.7 years; all were male and half of were Black patients. The gender imbalance was due to the predominantly male patient population at Memphis VAMC. Among 111 patients with HCV infection and HCC, 68 patients were treated for HCV infection and had significantly improved OS and PFS compared with the nontreatment group. The median 5-year OS was 44.6 months (95% CI, 966-3202) in the treated HCV infection group compared with 15.1 months in the untreated HCV infection group with a Wilcoxon P = .0005 (Figure 1). Similarly, patients treated for HCV infection had a significantly better 5-year PFS of 15.3 months (95% CI, 294-726) compared with the nontreatment group 9.5 months (95% CI, 205-405) with a Wilcoxon P = .04 (Figure 2).

Among 68 patients treated for HCV infection, 51 achieved SVR, and 34 achieved SVR after the diagnosis of HCC. Patients who achieved SVR had an improved 5-year OS when compared with patients who did not achieve SVR (median 65.8 months [95% CI, 1222-NA] vs 15.7 months [95% CI, 242-853], Wilcoxon P < .001) (Figure 3). Similarly, patients with SVR had improved 5-year PFS when compared with the non-SVR group (median 20.5 months [95% CI, 431-914] vs 8.9 months [95% CI, 191-340], Wilcoxon P = .007 (Figure 4). Achievement of SVR after HCC diagnosis suggests a significantly improved OS (HR 0.37) compared with achievement prior to HCC diagnosis (HR, 0.65; 95% CI, 0.23-1.82, P = .41)

Discussion

The survival benefit of HCV eradication and achieving SVR status has been well established in patients with HCC.¹³ In a retrospective cohort study of 250 patients with HCV infection who had received curative treatment for HCC, multivariate analysis demonstrated that achieving SVR is an independent predictor of OS.¹⁴ The 3-year and 5-year OS rates were 97% and 94% for the SVR group, and 91% and 60% for the non‐SVR group, respectively (P < .001). Similarly, according to Sou and colleagues, of 122 patients with HCV-related HCC, patients with SVR had longer OS than patients with no SVR (P = .04).¹⁵ One of the hypotheses that could explain the survival benefit in patients who achieved SVR is the effect of achieving SVR in reducing persistent liver inflammation and associated liver mortality, and therefore lowering risks of complication in patients with HCC.¹⁶ In our study, multivariate analysis shows that achieving SVR is associated with significant improved OS (HR, 0.33). In contrast, patients with HCC who have not achieved SVR are associated with worse survival (HR, 3.24). This finding supports early treatment of HCV to obtain SVR in HCV-related patients with HCC, even after development of HCC.

Among 68 patients treated for HCV infection, 45 patients were treated after HCC diagnosis, and 34 patients achieved SVR after HCC diagnosis. The average time between HCV infection treatment after HCC diagnosis was 6 months. Our data suggested that achievement of SVR after HCC diagnosis suggests an improved OS (HR, 0.37) compared with achievement prior to HCC diagnosis (HR, 0.65; 95% CI,0.23-1.82; P = .41). This lack of statistical significance is likely due to small sample size of patients achieving SVR prior to HCC diagnosis. Our results are consistent with the findings regarding the efficacy and timing of DAA treatment in patients with active HCC. According to Singal and colleagues, achieving SVR after DAA therapy may result in improved liver function and facilitate additional HCC-directed therapy, which potentially improves survival.^17-19

Nagaoki and colleagues found that there was no significant difference in OS in patients with HCC between the DAA and IFN groups. According to the study, the 3-year and 5-year OS rates were 96% and 96% for DAA patients and 93% and 73% for IFN patients, respectively (P = .16).¹⁴ This finding is consistent with the results of our study. HCV treatment type (IFN vs DAA) was not found to be associated with either OS or PFS time, regardless of time period.

Limitations

Our findings were limited in that our study population is too small to conduct further subset analysis that would allow statistical significance of those subsets, such as the suggested benefit of SVR in patients who presented with HCC after antiviral therapy. Another limitation is the all-male population, likely a result of the older veteran population at the Memphis VAMC. The mean age at diagnosis was 65 years, which is slightly higher than the general population. Compared to the SEER database, HCC is most frequently diagnosed among people aged 55 to 64 years.²³ The age difference was likely due to our aging veteran population.

Further studies are needed to determine the significance of SVR on HCC recurrence and treatment. Immunotherapy is now first-line treatment for patients with local advanced HCC. All the immunotherapy studies excluded patients with active HCV infection. Hence, we need more data on HCV treatment timing among patients scheduled to start treatment with immunotherapy.

Conclusions

In a population of older veterans, treatment of HCV infection leads to OS benefit among patients with HCC. In addition, patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs IFN-based regimen, did not show significant survival benefit.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Key clinical point: The addition of bone resorption inhibitors (BRIs) to abiraterone acetate with prednisone prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) and bone metastases. The OS was similar regardless of the BRI type used.

Major finding: The median follow-up was 23.5 months. Concomitant use of BRIs was reported in 29.0% of patients. BRI use was associated with OS improvement (31.8 months vs 23.0 months; hazard ratio [HR], 0.65; P less than .001) and shorter time to the first skeletal-related event (32.4 months vs 42.7 months; HR, 1.27; P = .04). Both denosumab and zoledronic acid were associated with similar OS (P = .79).

Study details: A retrospective study of 745 consecutive patients with metastatic CRPC and bone metastases who received abiraterone acetate plus prednisone between 2013 and 2016.

Disclosures: No funding source was reported. The authors received grants, personal fees, travel expenses, and research funding from and/or owned stocks in pharmaceutical companies outside the submitted work.

Source: Francini E et al. JAMA Netw Open. 2021 Jul 22. doi: 10.1001/jamanetworkopen.2021.16536.

Key clinical point: The addition of bone resorption inhibitors (BRIs) to abiraterone acetate with prednisone prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) and bone metastases. The OS was similar regardless of the BRI type used.

Major finding: The median follow-up was 23.5 months. Concomitant use of BRIs was reported in 29.0% of patients. BRI use was associated with OS improvement (31.8 months vs 23.0 months; hazard ratio [HR], 0.65; P less than .001) and shorter time to the first skeletal-related event (32.4 months vs 42.7 months; HR, 1.27; P = .04). Both denosumab and zoledronic acid were associated with similar OS (P = .79).

Study details: A retrospective study of 745 consecutive patients with metastatic CRPC and bone metastases who received abiraterone acetate plus prednisone between 2013 and 2016.

Disclosures: No funding source was reported. The authors received grants, personal fees, travel expenses, and research funding from and/or owned stocks in pharmaceutical companies outside the submitted work.

Source: Francini E et al. JAMA Netw Open. 2021 Jul 22. doi: 10.1001/jamanetworkopen.2021.16536.

Key clinical point: The addition of bone resorption inhibitors (BRIs) to abiraterone acetate with prednisone prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) and bone metastases. The OS was similar regardless of the BRI type used.

Major finding: The median follow-up was 23.5 months. Concomitant use of BRIs was reported in 29.0% of patients. BRI use was associated with OS improvement (31.8 months vs 23.0 months; hazard ratio [HR], 0.65; P less than .001) and shorter time to the first skeletal-related event (32.4 months vs 42.7 months; HR, 1.27; P = .04). Both denosumab and zoledronic acid were associated with similar OS (P = .79).

Study details: A retrospective study of 745 consecutive patients with metastatic CRPC and bone metastases who received abiraterone acetate plus prednisone between 2013 and 2016.

Disclosures: No funding source was reported. The authors received grants, personal fees, travel expenses, and research funding from and/or owned stocks in pharmaceutical companies outside the submitted work.

Source: Francini E et al. JAMA Netw Open. 2021 Jul 22. doi: 10.1001/jamanetworkopen.2021.16536.

Key clinical point: In patients with localized prostate cancer, the use of phosphodiesterase (PDE)-5 inhibitors improve survival.

Major finding: The patients who received PDE-5 inhibitors vs those who did not showed a significant improvement in biochemical recurrence-free (BCRF) survival (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.34-0.56) and overall survival (OS; HR, 0.65; 95% CI, 0.45-0.94) at 10 years. In PDE-5 inhibitors users vs nonusers, BCRF survival was 93.2% vs 85.3% and OS was 95.8% vs 94.5%.

Study details: A retrospective cohort study of 3,100 patients with prostate cancer who underwent radical prostatectomy between 2003 and 2015; 1,372 patients received PDE-5 inhibitors.

Disclosures: The study was supported by National Cancer Institute. The authors declared no conflict of interests.

Source: Danley KT et al. Urol Oncol. 2021 Jul 18. doi: 10.1016/j.urolonc.2021.05.031.

Key clinical point: In patients with localized prostate cancer, the use of phosphodiesterase (PDE)-5 inhibitors improve survival.

Major finding: The patients who received PDE-5 inhibitors vs those who did not showed a significant improvement in biochemical recurrence-free (BCRF) survival (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.34-0.56) and overall survival (OS; HR, 0.65; 95% CI, 0.45-0.94) at 10 years. In PDE-5 inhibitors users vs nonusers, BCRF survival was 93.2% vs 85.3% and OS was 95.8% vs 94.5%.

Study details: A retrospective cohort study of 3,100 patients with prostate cancer who underwent radical prostatectomy between 2003 and 2015; 1,372 patients received PDE-5 inhibitors.

Disclosures: The study was supported by National Cancer Institute. The authors declared no conflict of interests.

Source: Danley KT et al. Urol Oncol. 2021 Jul 18. doi: 10.1016/j.urolonc.2021.05.031.

Key clinical point: In patients with localized prostate cancer, the use of phosphodiesterase (PDE)-5 inhibitors improve survival.

Major finding: The patients who received PDE-5 inhibitors vs those who did not showed a significant improvement in biochemical recurrence-free (BCRF) survival (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.34-0.56) and overall survival (OS; HR, 0.65; 95% CI, 0.45-0.94) at 10 years. In PDE-5 inhibitors users vs nonusers, BCRF survival was 93.2% vs 85.3% and OS was 95.8% vs 94.5%.

Study details: A retrospective cohort study of 3,100 patients with prostate cancer who underwent radical prostatectomy between 2003 and 2015; 1,372 patients received PDE-5 inhibitors.

Disclosures: The study was supported by National Cancer Institute. The authors declared no conflict of interests.

Source: Danley KT et al. Urol Oncol. 2021 Jul 18. doi: 10.1016/j.urolonc.2021.05.031.

Key clinical point: Positive prostate-specific membrane antigen positron emission tomography (PSMA PET) findings prior to salvage radiotherapy (SRT) are associated with worse metastasis-free survival (MFS) in patients with recurrent prostate cancer.

Major finding: In 155 patients who underwent PSMA PET prior to SRT, 31.6% had positive PSMA PET. After propensity score matching, 5-year MFS was significantly lower in patients with “positive PSMA PET” vs those who did not undergo PSMA PET (48.5% vs 92.3%; P < .001). Positive PSMA PET imaging was associated with worse MFS compared with “no PSMA PET” (hazard ratio, 13.8; P < .001).

Study design: A retrospective study of 1,599 patients with recurrent prostate cancer who received salvage radiotherapy after biochemical recurrence.

Disclosures: The study received no funding. The authors declared no conflict of interests.

Source: Wenzel M et al. Urol Oncol. 2021 Jul 31. doi: 10.1016/j.urolonc.2021.06.008.

Key clinical point: Positive prostate-specific membrane antigen positron emission tomography (PSMA PET) findings prior to salvage radiotherapy (SRT) are associated with worse metastasis-free survival (MFS) in patients with recurrent prostate cancer.

Major finding: In 155 patients who underwent PSMA PET prior to SRT, 31.6% had positive PSMA PET. After propensity score matching, 5-year MFS was significantly lower in patients with “positive PSMA PET” vs those who did not undergo PSMA PET (48.5% vs 92.3%; P < .001). Positive PSMA PET imaging was associated with worse MFS compared with “no PSMA PET” (hazard ratio, 13.8; P < .001).

Study design: A retrospective study of 1,599 patients with recurrent prostate cancer who received salvage radiotherapy after biochemical recurrence.

Disclosures: The study received no funding. The authors declared no conflict of interests.

Source: Wenzel M et al. Urol Oncol. 2021 Jul 31. doi: 10.1016/j.urolonc.2021.06.008.

Key clinical point: Positive prostate-specific membrane antigen positron emission tomography (PSMA PET) findings prior to salvage radiotherapy (SRT) are associated with worse metastasis-free survival (MFS) in patients with recurrent prostate cancer.

Major finding: In 155 patients who underwent PSMA PET prior to SRT, 31.6% had positive PSMA PET. After propensity score matching, 5-year MFS was significantly lower in patients with “positive PSMA PET” vs those who did not undergo PSMA PET (48.5% vs 92.3%; P < .001). Positive PSMA PET imaging was associated with worse MFS compared with “no PSMA PET” (hazard ratio, 13.8; P < .001).

Study design: A retrospective study of 1,599 patients with recurrent prostate cancer who received salvage radiotherapy after biochemical recurrence.

Disclosures: The study received no funding. The authors declared no conflict of interests.

Source: Wenzel M et al. Urol Oncol. 2021 Jul 31. doi: 10.1016/j.urolonc.2021.06.008.

Key clinical point: In patients with Gleason grade 3+4 prostate cancer treated with brachytherapy, high prostate-specific antigen (PSA) levels are associated with an elevated risk for prostate cancer-specific mortality (PCSM).

Major finding: The median follow-up was 7.8 years. The PSA levels of 10.1-20.0 ng/mL vs 4.0-10.0 ng/mL were associated with higher PCSM in patients who received brachytherapy alone (adjusted hazard ratio [aHR], 5.55; P < .001) and those who received brachytherapy with androgen deprivation treatment (ADT; aHR, 4.17; P = .02).

Study details: A retrospective study of 1,920 patients with Gleason grade 3+4 prostate cancer who received brachytherapy with or without ADT.

Disclosures: No funding source was reported. The authors did not report any conflict of interests.

Source: Yang DD et al. Urol Oncol. 2021 Jul 24. doi: 10.1016/j.urolonc.2021.06.022.

Key clinical point: In patients with Gleason grade 3+4 prostate cancer treated with brachytherapy, high prostate-specific antigen (PSA) levels are associated with an elevated risk for prostate cancer-specific mortality (PCSM).

Major finding: The median follow-up was 7.8 years. The PSA levels of 10.1-20.0 ng/mL vs 4.0-10.0 ng/mL were associated with higher PCSM in patients who received brachytherapy alone (adjusted hazard ratio [aHR], 5.55; P < .001) and those who received brachytherapy with androgen deprivation treatment (ADT; aHR, 4.17; P = .02).

Study details: A retrospective study of 1,920 patients with Gleason grade 3+4 prostate cancer who received brachytherapy with or without ADT.

Disclosures: No funding source was reported. The authors did not report any conflict of interests.

Source: Yang DD et al. Urol Oncol. 2021 Jul 24. doi: 10.1016/j.urolonc.2021.06.022.

Key clinical point: In patients with Gleason grade 3+4 prostate cancer treated with brachytherapy, high prostate-specific antigen (PSA) levels are associated with an elevated risk for prostate cancer-specific mortality (PCSM).

Major finding: The median follow-up was 7.8 years. The PSA levels of 10.1-20.0 ng/mL vs 4.0-10.0 ng/mL were associated with higher PCSM in patients who received brachytherapy alone (adjusted hazard ratio [aHR], 5.55; P < .001) and those who received brachytherapy with androgen deprivation treatment (ADT; aHR, 4.17; P = .02).

Study details: A retrospective study of 1,920 patients with Gleason grade 3+4 prostate cancer who received brachytherapy with or without ADT.

Disclosures: No funding source was reported. The authors did not report any conflict of interests.

Source: Yang DD et al. Urol Oncol. 2021 Jul 24. doi: 10.1016/j.urolonc.2021.06.022.

Key clinical point: Nomograms to predict survival and prostate-specific antigen (PSA) response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177 prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) radionuclide treatment have been developed and externally validated.

Major finding: The median follow-up was 21.5 months. The concordance index of the overall survival model was 0.71 and PSA-progression-free survival model was 0.70. The model for PSA decline of 50% or more had a sensitivity of 94%, negative predictive value of 89%, and specificity of 38%.

Study details: Nomograms for predicting outcomes after Lu-PSMA treatment were developed (n=196) and validated (n=74) using clinical trial and real-world data of patients with late-stage mCRPC.

Disclosures: The study was supported by Prostate Cancer Foundation. The authors declared consulting, personal fees, travel fees, grants, honoraria, nonfinancial support, and patents outside this work. Dr. J Czernin reported being a founder and board member of and holding equity in Sofie Biosciences and Trethera Therapeutics.

Source: Gafita A et al. Lancet Oncol. 2021 Jul 8. doi: 10.1016/S1470-2045(21)00274-6.

Key clinical point: Nomograms to predict survival and prostate-specific antigen (PSA) response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177 prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) radionuclide treatment have been developed and externally validated.

Major finding: The median follow-up was 21.5 months. The concordance index of the overall survival model was 0.71 and PSA-progression-free survival model was 0.70. The model for PSA decline of 50% or more had a sensitivity of 94%, negative predictive value of 89%, and specificity of 38%.

Study details: Nomograms for predicting outcomes after Lu-PSMA treatment were developed (n=196) and validated (n=74) using clinical trial and real-world data of patients with late-stage mCRPC.

Disclosures: The study was supported by Prostate Cancer Foundation. The authors declared consulting, personal fees, travel fees, grants, honoraria, nonfinancial support, and patents outside this work. Dr. J Czernin reported being a founder and board member of and holding equity in Sofie Biosciences and Trethera Therapeutics.

Source: Gafita A et al. Lancet Oncol. 2021 Jul 8. doi: 10.1016/S1470-2045(21)00274-6.

Key clinical point: Nomograms to predict survival and prostate-specific antigen (PSA) response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177 prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) radionuclide treatment have been developed and externally validated.

Major finding: The median follow-up was 21.5 months. The concordance index of the overall survival model was 0.71 and PSA-progression-free survival model was 0.70. The model for PSA decline of 50% or more had a sensitivity of 94%, negative predictive value of 89%, and specificity of 38%.

Study details: Nomograms for predicting outcomes after Lu-PSMA treatment were developed (n=196) and validated (n=74) using clinical trial and real-world data of patients with late-stage mCRPC.

Disclosures: The study was supported by Prostate Cancer Foundation. The authors declared consulting, personal fees, travel fees, grants, honoraria, nonfinancial support, and patents outside this work. Dr. J Czernin reported being a founder and board member of and holding equity in Sofie Biosciences and Trethera Therapeutics.

Source: Gafita A et al. Lancet Oncol. 2021 Jul 8. doi: 10.1016/S1470-2045(21)00274-6.

Key clinical point: Talazoparib shows antitumor response in heavily pretreated patients with metastatic, castration-resistant prostate cancer (CRPC) with alterations in DNA damage repair (DDR) genes.

Major finding: The median follow-up was 16.4 months. The confirmed objective response rate (ORR) was 29.8%. The ORR was 46% in patients with BRCA2 alterations and 50% in those with BRCA1 alterations. Grade 3-4 adverse event rate was 48%; anemia, thrombocytopenia, and neutropenia were most common.

Study details: A multicenter, phase 2 TALAPRO-1 trial of 127 heavily pretreated patients with metastatic, CRPC with alterations in DDR genes who received talazoparib; 104 patients had measurable soft tissue disease.

Disclosures: This study was funded by Pfizer. The authors received grants/funding, consulting fees, travel/accommodation expenses, and/or honoraria from and/or reported employment and/or stock ownership in companies. Dr. JS de Bono also reported patent ownership.

Source: de Bono JS et al. Lancet Oncol. 2021 Aug 10. doi: 10.1016/ S1470-2045(21)00376-4.

Key clinical point: Talazoparib shows antitumor response in heavily pretreated patients with metastatic, castration-resistant prostate cancer (CRPC) with alterations in DNA damage repair (DDR) genes.

Major finding: The median follow-up was 16.4 months. The confirmed objective response rate (ORR) was 29.8%. The ORR was 46% in patients with BRCA2 alterations and 50% in those with BRCA1 alterations. Grade 3-4 adverse event rate was 48%; anemia, thrombocytopenia, and neutropenia were most common.

Study details: A multicenter, phase 2 TALAPRO-1 trial of 127 heavily pretreated patients with metastatic, CRPC with alterations in DDR genes who received talazoparib; 104 patients had measurable soft tissue disease.

Disclosures: This study was funded by Pfizer. The authors received grants/funding, consulting fees, travel/accommodation expenses, and/or honoraria from and/or reported employment and/or stock ownership in companies. Dr. JS de Bono also reported patent ownership.

Source: de Bono JS et al. Lancet Oncol. 2021 Aug 10. doi: 10.1016/ S1470-2045(21)00376-4.

Key clinical point: Talazoparib shows antitumor response in heavily pretreated patients with metastatic, castration-resistant prostate cancer (CRPC) with alterations in DNA damage repair (DDR) genes.

Major finding: The median follow-up was 16.4 months. The confirmed objective response rate (ORR) was 29.8%. The ORR was 46% in patients with BRCA2 alterations and 50% in those with BRCA1 alterations. Grade 3-4 adverse event rate was 48%; anemia, thrombocytopenia, and neutropenia were most common.

Study details: A multicenter, phase 2 TALAPRO-1 trial of 127 heavily pretreated patients with metastatic, CRPC with alterations in DDR genes who received talazoparib; 104 patients had measurable soft tissue disease.

Disclosures: This study was funded by Pfizer. The authors received grants/funding, consulting fees, travel/accommodation expenses, and/or honoraria from and/or reported employment and/or stock ownership in companies. Dr. JS de Bono also reported patent ownership.

Source: de Bono JS et al. Lancet Oncol. 2021 Aug 10. doi: 10.1016/ S1470-2045(21)00376-4.

Key clinical point: A network meta-analysis suggests that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, had similar efficacy and safety to parenteral degarelix.

Major finding: Compared with GnRH agonists, there was no significant difference in castration rate at 12 months with relugolix (risk ratio [RR], 1.09; 95% credible interval [CrI], 0.95-1.23) and degarelix (RR, 0.98; 95% CrI, 0.91-1.06). Efficacy ranking analyses showed that relugolix was the most effective medical castration drug to induce sustained castration at 12 months. Compared with GnRH agonists, adverse events rates were similar with relugolix (RR, 0.99; 95% CrI, 0.6-1.6) and degarelix (RR, 1.1; 95% CrI, 0.75-1.35).

Study design: A network meta-analysis of 4 studies compared relugolix and degarelix with GnRH antagonists in 2,059 patients with advanced prostate cancer.

Disclosures: The study did not receive any funding. The authors declared no competing interest.

Source: Motlagh RS et al. Eur Urol Oncol. 2021 Jul 20. doi: 10.1016/j.euo.2021.07.002.

Key clinical point: A network meta-analysis suggests that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, had similar efficacy and safety to parenteral degarelix.

Major finding: Compared with GnRH agonists, there was no significant difference in castration rate at 12 months with relugolix (risk ratio [RR], 1.09; 95% credible interval [CrI], 0.95-1.23) and degarelix (RR, 0.98; 95% CrI, 0.91-1.06). Efficacy ranking analyses showed that relugolix was the most effective medical castration drug to induce sustained castration at 12 months. Compared with GnRH agonists, adverse events rates were similar with relugolix (RR, 0.99; 95% CrI, 0.6-1.6) and degarelix (RR, 1.1; 95% CrI, 0.75-1.35).

Study design: A network meta-analysis of 4 studies compared relugolix and degarelix with GnRH antagonists in 2,059 patients with advanced prostate cancer.

Disclosures: The study did not receive any funding. The authors declared no competing interest.

Source: Motlagh RS et al. Eur Urol Oncol. 2021 Jul 20. doi: 10.1016/j.euo.2021.07.002.

Key clinical point: A network meta-analysis suggests that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, had similar efficacy and safety to parenteral degarelix.

Major finding: Compared with GnRH agonists, there was no significant difference in castration rate at 12 months with relugolix (risk ratio [RR], 1.09; 95% credible interval [CrI], 0.95-1.23) and degarelix (RR, 0.98; 95% CrI, 0.91-1.06). Efficacy ranking analyses showed that relugolix was the most effective medical castration drug to induce sustained castration at 12 months. Compared with GnRH agonists, adverse events rates were similar with relugolix (RR, 0.99; 95% CrI, 0.6-1.6) and degarelix (RR, 1.1; 95% CrI, 0.75-1.35).

Study design: A network meta-analysis of 4 studies compared relugolix and degarelix with GnRH antagonists in 2,059 patients with advanced prostate cancer.

Disclosures: The study did not receive any funding. The authors declared no competing interest.

Source: Motlagh RS et al. Eur Urol Oncol. 2021 Jul 20. doi: 10.1016/j.euo.2021.07.002.