At the May 18 PCSANM support meeting, Dr. Lindberg referred to 3 news articles about research studies.
Here are links to them and /or summaries. Full articles usually require enrollment in various websites for medical professionals, at a cost.
As always, share with your doctor and ask for their recommendation.
1.
AUA Offers Evidence-Based Guide For Sequencing CRPC Therapies castration-resistant prostate cancer (CRPC)
http://www.ncbi.nlm.nih.gov/pubmed/23123372
Patients with castration-resistant prostate cancer (CRPC) should receive
treatment supported by the best evidence for specific disease characteristics,
according to a clinical guideline developed by the American Urological
Association (AUA).
The guideline, the AUA’s first for the treatment of CRPC, outlines a course of action based on six “index patients,” ranging from men with asymptomatic, nonmetastatic CRPC to those with symptomatic, metastatic disease, poor performance status, and previous exposure to docetaxel chemotherapy. The guideline was presented today during the AUA’s 2013 Annual Meeting in San Diego, California.
“The timing was right for a guideline, because there is a lot going on in the field of prostate cancer, including the recent approval of four new therapies for castration-resistant prostate cancer and the hope that more new agents are coming,” said guideline committee chair Michael Cookson, MD, of Vanderbilt University in Nashville, Tennessee.
“When you have a lot of management or treatment options that
are extending the life and improving the quality of life of these patients, it’s
confusing for practitioners in terms of when to use them, knowing when the
agents are appropriate,” Cookson continued. “In developing this guideline, we hoped to cast a net, look into what’s available, and then put the information into a user-friendly clinical algorithm for practicing
physicians.”
Historically, men with metastatic CRPC (mCRPC) have had a median survival of less than 2 years. However, the approval of four new agents in
a span of less than 3 years has helped improve survival, even though mCRPC remains an incurable disease, Cookson said in his introduction to the guideline at the AUA meeting.
“While greater availability of effective agents benefits patients, multiple options and sequencing may complicate decision making,” he said.
Following an extensive literature review that extended
to February 2013, members of the guideline-writing committee assembled a
clinical algorithm that recommended certain therapies at different stages of the disease. The authors organized the information and recommendations according to the applicability of therapies to six types of patients.
The index patients and their guideline therapies are based on presence or absence of metastatic disease, degree and severity of symptoms, performance status, and prior docetaxel therapy. The clinical document also addresses protection and preservation of bone health in all six types of patients.
Index patient 1 has asymptomatic, nonmetastatic CRPC, for which the AUA recommends observation with continued androgen deprivation therapy. Physicians may offer first-generation antiandrogens or androgen synthesis inhibitors to selected patients who are unwilling to accept observation. Physicians should not offer systemic chemotherapy or immunotherapy, except within the context of a clinical trial.
Index patient 2 has asymptomatic or minimally symptomatic mCRPC
and no history of exposure to docetaxel. For this patient, treating physicians
should offer abiraterone + prednisone, docetaxel, or sipuleucel-T, assuming the patient has good ECOG performance status. Because the agents have not been compared directly in head-to-head clinical trials, sequencing should be guided by toxicity profile, beginning with the least toxic agent, according to the AUA.
Patients who do not want or cannot be treated with a standard therapy can be offered first-generation antiandrogen therapy, assuming they have
good performance status.
Index patient 3 has symptomatic mCRPC, good performance status, and no prior exposure to docetaxel. According to the guideline, clinicians should first offer docetaxel to these patients, if they have good performance status. Alternatively, clinicians may offer abiraterone + prednisone. If such a patient does not want or cannot be treated with standard therapies, clinicians may offer ketoconazole + steroid, mitoxantrone, or radionuclide therapy. According to the AUA, physicians should not offer estramustine or
sipuleucel-T to patients who meet index 3 criteria.
Index 4 patients have symptomatic mCRPC and no prior treatment with docetaxel but have poor performance status. The AUA advises clinicians that they may offer abiraterone + prednisone to these patients or, if the patients refuse or are unable to receive that course of treatment, ketoconazole + steroid or radionuclide therapy.
In select index 4 patients whose performance status
is directly related to the cancer, clinicians may offer docetaxel or
mitoxantrone but should not offer sipuleucel-T.
Index patient 5 has symptomatic mCRPC, good performance status, and a history of treatment with docetaxel. For these patients, clinicians should offer abiraterone + prednisone, cabazitaxel, or enzalutamide. In select patients who received abiraterone before docetaxel, clinicians should offer cabazitaxel or enzalutamide.
In situations wherein abiraterone, cabazitaxel, or enzalutamide are unavailable, ketoconazole + steroid may be offered. Index 5 patients might also be offered retreatment with docetaxel if they discontinued because of reversible side effects and were benefiting from the agent at the time of
discontinuation.
Index patient 6 has symptomatic mCRPC, poor performance
status, and prior docetaxel treatment. These patients should be offered
palliative care, or, alternatively for selected patients, abiraterone +
prednisone, enzalutamide, ketoconazole + steroid, or radionuclide
therapy.
“Of course there is flexibility in the guideline, but clinicians
should recognize that the level of evidence dictates the statements and
recommendations we can make,” said Cookson. “The AUA has set the bar high in terms of supporting evidence, and we followed the criteria to ensure that clinicians get the most evidence-based information possible.”
The AUA recommends that clinicians address bone health for all patients, regardless of index status. Clinicians should offer preventive therapy for fractures and skeletal-related events (SREs). For patients with bony metastases, treating physicians may offer denosumab or zoledronic acid for prevention of SREs.
“Although our primary objective was treatment of the disease and
true survival benefit, bone health is important to all patients with
castration-resistant prostate cancer,” said Cookson. “We recognized this and
addressed it in the guideline.” - See more at:
http://www.onclive.com/conference-coverage/aua-2013/AUA-Offers-Evidence-Based-Guide-For-Sequencing-CRPC-Therapies#sthash.W8bIKCMt.dpuf
2.
Operational characteristics of (11)c-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment.
Purpose
We examined the performance of 11C-choline positron emission tomography/computerized tomography for its ability to delineate prostate cancer distribution and extent after initial therapy.
Materials and Methods
A consecutive series retrospective review was performed of all patients with prostate cancer who were evaluated using 11C-choline positron emission tomography/computerized tomography from September 2007 to November 2010 at the Mayo Clinic. Statistical analysis was performed to
determine the sensitivity, specificity, positive predictive value, negative
predictive value and prostate specific antigen threshold for the detection of
recurrent lesions.
Results
In the study period 176 patients with biochemical recurrence after primary treatment failure underwent 11C-choline positron emission tomography/computerized tomography. Using patient based analysis 11C-choline positron emission tomography yielded a sensitivity, specificity, positive predictive value and negative predictive value of 93%,
76%, 91% and 81%, respectively. Of the 176 positron emission
tomography/computerized tomography scans performed 56 (32%) were deemed clinically useful as defined by the ability to identify lesions not delineated using conventional imaging, thereby prompting changes in clinical management.
The optimal prostate specific antigen for lesion detection was 2.0 ng/ml. On
multivariate analysis prostate specific antigen at positron emission tomography
(HR 1.37, p = 0.04) and clinical stage at initial diagnosis of prostate cancer
(HR 5.19, p = 0.0035) were significant predictors of positive 11C-choline positron emission tomography/computerized tomography.
Conclusions
11C-choline positron emission tomography/computerized tomography performs well in men with biochemical recurrence after primary treatment failure. The optimal prostate specific antigen value for lesion detection is approximately 2.0 ng/ml. We found that 11C-choline positron emission tomography/computerized tomography substantially enhances the rate of prostate cancer lesion detection by approximately 32% beyond what can be garnered using conventional imaging techniques and at a lower prostate specific antigen value.
Key Words: prostatic neoplasms, recurrence, positron-emission tomography and computed tomography, choline
Abbreviations and Acronyms: ADT, androgen deprivation therapy, BCR,
biochemical recurrence, CT, computerized tomography, MRI, magnetic resonance imaging, NPV, negative predictive value, PET, positron emission tomography, PPV, positive predictive value, PSA, prostate specific antigen, RP, radical prostatectomy
http://www.ncbi.nlm.nih.gov/pubmed/23123372
3.
Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: Results from the randomised, placebo-controlled Avodart after radical therapy for prostate cancer study (ARTS)
http://www.ncbi.nlm.nih.gov/pubmed/23176897
Abstract
BACKGROUND:
Rising prostate-specific antigen (PSA) levels after radical therapy are
indicative of recurrent or residual prostate cancer (PCa). This biochemical
recurrence typically predates clinically detectable metastatic disease by
several years. Management of patients with biochemical recurrence is
controversial.
OBJECTIVE:
To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.
DESIGN, SETTING, AND PARTICIPANTS:
Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.
INTERVENTION:
The 5α-reductase inhibitor, dutasteride.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.
RESULTS AND LIMITATIONS:
Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group)Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p<0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35-76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p<0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53-75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.
CONCLUSIONS:
Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.
CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT00558363.
Here are links to them and /or summaries. Full articles usually require enrollment in various websites for medical professionals, at a cost.
As always, share with your doctor and ask for their recommendation.
1.
AUA Offers Evidence-Based Guide For Sequencing CRPC Therapies castration-resistant prostate cancer (CRPC)
http://www.ncbi.nlm.nih.gov/pubmed/23123372
Patients with castration-resistant prostate cancer (CRPC) should receive
treatment supported by the best evidence for specific disease characteristics,
according to a clinical guideline developed by the American Urological
Association (AUA).
The guideline, the AUA’s first for the treatment of CRPC, outlines a course of action based on six “index patients,” ranging from men with asymptomatic, nonmetastatic CRPC to those with symptomatic, metastatic disease, poor performance status, and previous exposure to docetaxel chemotherapy. The guideline was presented today during the AUA’s 2013 Annual Meeting in San Diego, California.
“The timing was right for a guideline, because there is a lot going on in the field of prostate cancer, including the recent approval of four new therapies for castration-resistant prostate cancer and the hope that more new agents are coming,” said guideline committee chair Michael Cookson, MD, of Vanderbilt University in Nashville, Tennessee.
“When you have a lot of management or treatment options that
are extending the life and improving the quality of life of these patients, it’s
confusing for practitioners in terms of when to use them, knowing when the
agents are appropriate,” Cookson continued. “In developing this guideline, we hoped to cast a net, look into what’s available, and then put the information into a user-friendly clinical algorithm for practicing
physicians.”
Historically, men with metastatic CRPC (mCRPC) have had a median survival of less than 2 years. However, the approval of four new agents in
a span of less than 3 years has helped improve survival, even though mCRPC remains an incurable disease, Cookson said in his introduction to the guideline at the AUA meeting.
“While greater availability of effective agents benefits patients, multiple options and sequencing may complicate decision making,” he said.
Following an extensive literature review that extended
to February 2013, members of the guideline-writing committee assembled a
clinical algorithm that recommended certain therapies at different stages of the disease. The authors organized the information and recommendations according to the applicability of therapies to six types of patients.
The index patients and their guideline therapies are based on presence or absence of metastatic disease, degree and severity of symptoms, performance status, and prior docetaxel therapy. The clinical document also addresses protection and preservation of bone health in all six types of patients.
Index patient 1 has asymptomatic, nonmetastatic CRPC, for which the AUA recommends observation with continued androgen deprivation therapy. Physicians may offer first-generation antiandrogens or androgen synthesis inhibitors to selected patients who are unwilling to accept observation. Physicians should not offer systemic chemotherapy or immunotherapy, except within the context of a clinical trial.
Index patient 2 has asymptomatic or minimally symptomatic mCRPC
and no history of exposure to docetaxel. For this patient, treating physicians
should offer abiraterone + prednisone, docetaxel, or sipuleucel-T, assuming the patient has good ECOG performance status. Because the agents have not been compared directly in head-to-head clinical trials, sequencing should be guided by toxicity profile, beginning with the least toxic agent, according to the AUA.
Patients who do not want or cannot be treated with a standard therapy can be offered first-generation antiandrogen therapy, assuming they have
good performance status.
Index patient 3 has symptomatic mCRPC, good performance status, and no prior exposure to docetaxel. According to the guideline, clinicians should first offer docetaxel to these patients, if they have good performance status. Alternatively, clinicians may offer abiraterone + prednisone. If such a patient does not want or cannot be treated with standard therapies, clinicians may offer ketoconazole + steroid, mitoxantrone, or radionuclide therapy. According to the AUA, physicians should not offer estramustine or
sipuleucel-T to patients who meet index 3 criteria.
Index 4 patients have symptomatic mCRPC and no prior treatment with docetaxel but have poor performance status. The AUA advises clinicians that they may offer abiraterone + prednisone to these patients or, if the patients refuse or are unable to receive that course of treatment, ketoconazole + steroid or radionuclide therapy.
In select index 4 patients whose performance status
is directly related to the cancer, clinicians may offer docetaxel or
mitoxantrone but should not offer sipuleucel-T.
Index patient 5 has symptomatic mCRPC, good performance status, and a history of treatment with docetaxel. For these patients, clinicians should offer abiraterone + prednisone, cabazitaxel, or enzalutamide. In select patients who received abiraterone before docetaxel, clinicians should offer cabazitaxel or enzalutamide.
In situations wherein abiraterone, cabazitaxel, or enzalutamide are unavailable, ketoconazole + steroid may be offered. Index 5 patients might also be offered retreatment with docetaxel if they discontinued because of reversible side effects and were benefiting from the agent at the time of
discontinuation.
Index patient 6 has symptomatic mCRPC, poor performance
status, and prior docetaxel treatment. These patients should be offered
palliative care, or, alternatively for selected patients, abiraterone +
prednisone, enzalutamide, ketoconazole + steroid, or radionuclide
therapy.
“Of course there is flexibility in the guideline, but clinicians
should recognize that the level of evidence dictates the statements and
recommendations we can make,” said Cookson. “The AUA has set the bar high in terms of supporting evidence, and we followed the criteria to ensure that clinicians get the most evidence-based information possible.”
The AUA recommends that clinicians address bone health for all patients, regardless of index status. Clinicians should offer preventive therapy for fractures and skeletal-related events (SREs). For patients with bony metastases, treating physicians may offer denosumab or zoledronic acid for prevention of SREs.
“Although our primary objective was treatment of the disease and
true survival benefit, bone health is important to all patients with
castration-resistant prostate cancer,” said Cookson. “We recognized this and
addressed it in the guideline.” - See more at:
http://www.onclive.com/conference-coverage/aua-2013/AUA-Offers-Evidence-Based-Guide-For-Sequencing-CRPC-Therapies#sthash.W8bIKCMt.dpuf
2.
Operational characteristics of (11)c-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment.
Purpose
We examined the performance of 11C-choline positron emission tomography/computerized tomography for its ability to delineate prostate cancer distribution and extent after initial therapy.
Materials and Methods
A consecutive series retrospective review was performed of all patients with prostate cancer who were evaluated using 11C-choline positron emission tomography/computerized tomography from September 2007 to November 2010 at the Mayo Clinic. Statistical analysis was performed to
determine the sensitivity, specificity, positive predictive value, negative
predictive value and prostate specific antigen threshold for the detection of
recurrent lesions.
Results
In the study period 176 patients with biochemical recurrence after primary treatment failure underwent 11C-choline positron emission tomography/computerized tomography. Using patient based analysis 11C-choline positron emission tomography yielded a sensitivity, specificity, positive predictive value and negative predictive value of 93%,
76%, 91% and 81%, respectively. Of the 176 positron emission
tomography/computerized tomography scans performed 56 (32%) were deemed clinically useful as defined by the ability to identify lesions not delineated using conventional imaging, thereby prompting changes in clinical management.
The optimal prostate specific antigen for lesion detection was 2.0 ng/ml. On
multivariate analysis prostate specific antigen at positron emission tomography
(HR 1.37, p = 0.04) and clinical stage at initial diagnosis of prostate cancer
(HR 5.19, p = 0.0035) were significant predictors of positive 11C-choline positron emission tomography/computerized tomography.
Conclusions
11C-choline positron emission tomography/computerized tomography performs well in men with biochemical recurrence after primary treatment failure. The optimal prostate specific antigen value for lesion detection is approximately 2.0 ng/ml. We found that 11C-choline positron emission tomography/computerized tomography substantially enhances the rate of prostate cancer lesion detection by approximately 32% beyond what can be garnered using conventional imaging techniques and at a lower prostate specific antigen value.
Key Words: prostatic neoplasms, recurrence, positron-emission tomography and computed tomography, choline
Abbreviations and Acronyms: ADT, androgen deprivation therapy, BCR,
biochemical recurrence, CT, computerized tomography, MRI, magnetic resonance imaging, NPV, negative predictive value, PET, positron emission tomography, PPV, positive predictive value, PSA, prostate specific antigen, RP, radical prostatectomy
http://www.ncbi.nlm.nih.gov/pubmed/23123372
3.
Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: Results from the randomised, placebo-controlled Avodart after radical therapy for prostate cancer study (ARTS)
http://www.ncbi.nlm.nih.gov/pubmed/23176897
Abstract
BACKGROUND:
Rising prostate-specific antigen (PSA) levels after radical therapy are
indicative of recurrent or residual prostate cancer (PCa). This biochemical
recurrence typically predates clinically detectable metastatic disease by
several years. Management of patients with biochemical recurrence is
controversial.
OBJECTIVE:
To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.
DESIGN, SETTING, AND PARTICIPANTS:
Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.
INTERVENTION:
The 5α-reductase inhibitor, dutasteride.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.
RESULTS AND LIMITATIONS:
Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group)Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p<0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35-76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p<0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53-75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.
CONCLUSIONS:
Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.
CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT00558363.