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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.