Hypofractionation, vessel-sparing RT techniques for prostate cancer yield good QOL

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”