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Ian M Thompson

Publications and source records attributed to Ian M Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2005

Lifetime implications and cost-effectiveness of using finasteride to prevent prostate cancer.

PURPOSE: We estimate the lifetime implications of daily treatment with finasteride following the results of the Prostate Cancer Prevention Trial (PCPT). In this trial, prostate cancer prevalence was reduced by 25%; however, an increase in the number of high-grade tumors among the treatment group necessitates the long-term projection of the likely benefits and costs. METHODS: We use a Markov decision analysis model with data from the trial, the SEER program, and published literature. The model measures the cost per life-year and cost per quality-adjusted life-year (QALY) gained for a cohort of men age 55 years who initiate preventive treatment with finasteride. RESULTS: Finasteride is associated with a gain of 6 life-years per 1000 men treated at an incremental cost of 1660000 dollars per life-year gained. The quality-adjusted analysis results in 46 QALYs gained per 1000 men treated at an incremental cost of 200000 dollars per QALY gained, due primarily to the favorable effects of finasteride on benign prostatic hyperplasia. Under the assumption that the increase in high-grade tumors observed among finasteride treated men is a pathologic artifact, the incremental costs are 290000 dollars per life-year gained and 130000 dollars per QALY gained. CONCLUSIONS: The cost burden associated with finasteride is substantial, while its survival benefit is small and only realized many years after initiating treatment. To achieve an incremental cost below 100000 dollars per QALY gained, the price of finasteride must be reduced by 50% from its current average wholesale price and finasteride must be shown to prevent high-grade as well as low-grade disease.

Aged↗
PubMed2005

Screening for prostate cancer: opportunities and challenges.

Prostate cancer screening with PSA and with digital rectal examination isa reality in the United States. Regardless of recent observations regarding the complexities of PSA interpretation, millions of U.S. men expect an annual PSA test and physicians have come to rely on the test, in combination with digital rectal examination, to assess for prostate cancer risk. What has become evident is that PSA can no longer be interpreted dichotomously as a simple yes or no. The test reflects a range of risk and PSA value must be merged with other risk factors of an individual man including ethnicity, family history, as well as the individual's risk aversion to complications from prostate cancer. The future of prostate cancer screening will be built upon incorporation of new biomarkers to the prediction of risk of disease. As these markers move forward in testing, it will no longer be acceptable to move these into clinical usage without formal validation studies and, because of the high frequency of prostate cancer in the general male population, these validation studies will almost certainly have to include measures of prognosis. It is the holy grail of cancer biomarker development to acquire a test that is positive in the man with clinically-aggressive prostate cancer but is negative in both the patient without disease and in the man with disease that will be of no clinical consequence over his lifetime.

Adenocarcinoma↗
PubMed2005

National cooperative group trials.

Now is the time to answer critical questions in the management of prostate cancer through enrollment in high-priority national phase 3 clinical trials. Studies of systemic therapy before and after local therapy are vitally important to determine whether early systemic interventions might delay cancer progression. Chemotherapy must be studied in earlier disease progression. Novel targeted therapies, such as vaccine therapy, angiogenesis inhibitors, and newer microtubule targeting agents, should be studied in all stages of progression. Despite these needs and the availability of systemic therapies, accrual to trials has been lagging. This article reviews the national cooperative group clinical trials, whether currently open or planned, and suggests practical strategies to improve accrual.

Adult↗
PubMed2005

Mechanisms of disease: Prostate cancer--a model for cancer chemoprevention in clinical practice.

Prostate cancer is a significant cause of cancer death, making it an attractive target for chemoprevention. Epidemiologic studies and the Prostate Cancer Prevention Trial indicate that chemoprevention is possible. Strategies for prevention include hormonal manipulation and limiting accumulation of genetic damage with anti-inflammatory agents and/or dietary antioxidants. Development of an effective chemoprevention strategy for prostate cancer is evolving and will likely serve as a model for chemoprevention of other adult malignancies.

Androgens↗
PubMed2005

The modulation of prostate cancer risk with alpha-tocopherol: a pilot randomized, controlled clinical trial.

PURPOSE: Studies suggest that vitamin E may decrease the risk of prostate cancer. The Prevention Research Veteran Affairs E-vitamin Nutrition Trial is a randomized, double-blind, placebo controlled study designed to assess the effects of vitamin E supplementation on biomarkers associated with prostate cancer risk in peripheral blood and prostate tissue. MATERIALS AND METHODS: A total of 44 patients with increased prostate specific antigen (PSA) and/or abnormal digital rectal examination on initial evaluation were randomized to receive 400 IU vitamin E (22) vs placebo (22). Serum vitamin E, PSA, dehydroepiandrosterone, testosterone and insulin-like growth factor-1 (IGF-1) were measured in the 2 groups at baseline and then at 3-month intervals. Results are reported in 28 patients (placebo in 14 and vitamin E in 14) who completed the treatment as specified by the protocol. RESULTS: Serum Vitamin E was significantly higher in patients on vitamin E supplementation. alpha-Tocopherol supplementation did not affect the levels of PSA, serum androgens (testosterone and dehydroepiandrosterone) or (IGF-1). CONCLUSIONS: Serum alpha-tocopherol is increased by oral supplementation of vitamin E. We found that alpha-tocopherol supplementation has no effect on serum androgens, IGF-1 or PSA. The lack of an effect of vitamin supplementation on PSA avoids any bias in the diagnosis of prostate cancer in vitamin E treated patients. Our results suggest that a decrease in prostate cancer risk with alpha-tocopherol is likely to occur through a mechanism that is nonhormonal and independent of IGF-1.

Antioxidants↗
PubMed2005

Prognostic features in men who died of prostate cancer.

PURPOSE: Since the advent of widespread prostate specific antigen (PSA) based screening in the United States, the risk of over diagnosis as well as delayed diagnosis due to existing PSA thresholds has become a concern. Treatment decision planning is generally linked to prognostic variables, most notably PSA, clinical stage and Gleason grade. We examined these and other prognostic variables in a cohort of men who ultimately died of prostate cancer. MATERIALS AND METHODS: Of 413 men with prostate cancer in a cohort in San Antonio, Texas between 1993 and 2003 who died of disease we identified 211 who died as a direct result of prostate cancer. In these cases we assessed presenting symptoms, PSA history, tumor stage and Gleason score at diagnosis. RESULTS: Of the 211 men 141 (67%) underwent screening for prostate cancer prior to diagnosis. Of 190 men with PSA data at diagnosis available 7 (3.7%) had PSA less than 4.0 ng/ml and 27 (14%) had PSA 4.0 to 10.0 ng/ml. Clinical stage distribution was cT1 in 21.1% of cases, cT2 in 50.7% and cT3 in 26.8%. Of 167 men for whom biopsy Gleason grade was available 16.8%, 16.2%, 24% and 43.1% had Gleason sum 5 or less, 6, 7 and 8 or higher, respectively. CONCLUSIONS: While most men who ultimately die of prostate cancer have poor prognostic features, a substantial number have features associated with a potentially good prognosis, including low PSA and low Gleason grade. Many men who died of prostate cancer had undergone prior screening. These data demonstrate the need for improved markers of prognosis and continued assessment of the efficacy of screening with PSA.

Adult↗
PubMed2005

Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial.

PURPOSE: Studies have shown that finasteride decreases prostate specific antigen (PSA) by approximately 50% during the first 12 months of use. We estimated the long-term effects of finasteride on PSA in men with and without a prostate cancer diagnosis at the end of the study. MATERIALS AND METHODS: We analyzed serial PSA in participants in the Prostate Cancer Prevention Trial who had an end of study biopsy (928 with cancer and 8,620 with negative biopsy) or an interim diagnosis of prostate cancer (671). Linear mixed effects regression models were fit to longitudinal PSA values beginning 1 year after randomization. RESULTS: In subjects with no cancer in the end of study biopsy PSA in the finasteride arm showed a median annual decrease of 2% [corrected] after year 1, while PSA in the control arm showed an annual increase of 3% (p <0.001). In end of study cases PSA increased annually by 6% (placebo) and 7% (finasteride). In those with interim diagnoses PSA increased by 11% (placebo) and 15% (finasteride) each year prior to diagnosis. Cases with high grade disease (Gleason 7 and above) had greater PSA increases than cases with low grade disease (p <0.001). CONCLUSIONS: In men who have been receiving finasteride for more than 1 year time varying adjustment factors may be needed to determine whether PSA is in the normal range. In the Prostate Cancer Prevention Trial cohort the adjustment factor required to preserve median PSA increased from 2 at 24 months to 2.5 at 7 years after the initiation of finasteride.

Aged↗
PubMed2005

Fusion rate of first tarsometatarsal arthrodesis in the modified Lapidus procedure and flatfoot reconstruction.

BACKGROUND: The purpose of this study was to determine the overall first tarsometatarsal joint (TMTJ) union rate in patients after they had a modified Lapidus procedure or a TMTJ arthrodesis as part of a flatfoot reconstruction. METHODS: We retrospectively reviewed the charts of 182 patients (201 feet) who had a modified Lapidus procedure or a TMTJ arthrodesis as part of a flatfoot reconstruction between May, 1997, and May, 2001; all had at least a 6-month followup. The data collected included age, gender, tobacco use, diabetic status, complications, and radiographic evidence of union. There were 167 women and 15 men. The right foot was operated on in 106 patients and the left foot in 95. The average age was 53 (range 11 to 87) years. RESULTS: First TMTJ arthrodesis healed uneventfully in 193 (96%), and eight (4%) had nonunions. Of those eight patients with nonunions, five had previous bunion surgeries, two were smokers, and one had diabetes. There were 25 (12%) patients with previous bunion surgeries and five of these (20%) had nonunions. Four patients (2%) had symptomatic nonunions resulting in revision. Of the 21 patients undergoing flatfoot reconstruction, none had a nonunion. CONCLUSION: One criticism of the modified Lapidus procedure is the unacceptable nonunion rate (10 to 12%). Out of the 201 feet, we had a 4% nonunion rate and a 2% revision rate, which is well below the reported nonunion rates. We also have found that patients with previous bunion surgery and recurrent deformity were at a higher risk for a nonunion. CLINICAL RELEVANCE: We believe that the modified Lapidus procedure and first TMTJ arthrodesis can achieve acceptable union rates and be successful for correcting hallux valgus with a hypermobile first ray and can also be applied to certain patients undergoing flatfoot reconstruction.

Adult↗
PubMed2004

Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker.

BACKGROUND: The widespread use of prostate-specific antigen (PSA) screening has had a tremendous impact on all aspects of the management of prostate carcinoma. Although PSA-based screening has resulted in a stage migration to more organ-confined tumors at the time of diagnosis, and has been temporally associated with a decrease in prostate carcinoma mortality, PSA screening is imperfect. A recent analysis of results from the Prostate Cancer Prevention Trial (PCPT) has provided insight into the positive predictive value of PSA in the so-called "normal" range. METHODS: The history of the discovery, initial studies, and subsequent widespread application of PSA screening is reviewed. RESULTS: The application of PSA for screening preceded the development of current prostate biopsy techniques and an upper limit of normal was established without complete disease ascertainment. More recent modifications of PSA-based screening have been adopted clinically without sufficient validation. With current methods, overdiagnosis of clinically unimportant disease almost certainly occurs and high-grade, aggressive disease may not be detected sufficiently early to allow successful treatment. CONCLUSIONS: To the authors' knowledge, the optimal upper limit of normal for PSA for prostate carcinoma screening is unknown. New biomarkers of disease are needed; these must be linked with disease prognosis and must be validated in rigorously designed clinical trials.

Biomarkers, Tumor↗
PubMed2004

Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.

BACKGROUND: The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less. METHODS: Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years. RESULTS: Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high-grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter. CONCLUSIONS: Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.

Aged↗
PubMed2004

What's new in the field of prostate cancer chemoprevention?

Chemoprevention trials for several malignancies are completed, planned, or underway. Prostate cancer is one of the most common forms of cancer and understandably has received considerable recent attention as a potential target for chemoprevention. This article examines chemoprevention trials for prostate cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of prostate cancer.

Antioxidants↗
PubMed2004

Implementation of the Prostate Cancer Prevention Trial (PCPT).

The Prostate Cancer Prevention Trial is a randomized double blind chemoprevention trial of 18,882 men. It is designed to test the difference in the histologically proven prostate cancer prevalence between a group of participants given finasteride and another given placebo for 7 years. We present an overview of the study design, details of the administrative structure of the study and a description of the successful implementation of the accrual phase.

Chemoprevention↗
PubMed2004

The potential role of cyclooxygenase-2 inhibitors and 5alpha-reductase inhibitors in the prevention of urologic conditions.

Prevention of urologic cancer is a new field for urology. It focuses attention on men and women who may not be under the regular care of physicians and are without symptoms of disease. Although risk factors (eg, smoking in bladder cancer, family history or African-American ethnicity in prostate cancer, cryptorchid testes in testis cancer, Von Hippel-Lindau disease in renal cell carcinoma) can identify individuals at a greater risk for genitourinary malignancies, most patients have no risk factors except gender and age. Thus, developing public health recommendations that will have a major impact on these diseases will be challenging. Prevention strategies will be held to a higher standard of safety than traditional cancer treatment unless populations at a high risk for disease can be identified. It will be necessary for urologists to monitor the field of disease prevention because of the high frequency of urologic malignancies and the growing elderly population in the United States. Urologists are frequently providers for and confidants of this patient population and must be able to counsel these men and women about the benefits and risks of such prevention strategies.

Adult↗
PubMed2004

Diagnosis and treatment of prostate cancer.

Many controversies surround the management of prostate cancer to include screening practices, diagnosis, and treatment options. The lack of randomized prospective studies comparing the various definitive treatment modalities currently available occasionally can make the decision process challenging for patients and their providers. In this setting of controversy, the cost of treating clinically localized prostate cancer is significant. In the face of these unanswered questions, this article summarizes some important principles regarding the diagnosis and treatment of prostate cancer. This review is limited to the diagnosis and management of clinically localized disease.

Adult↗
PubMed2004

Update on chemoprevention of prostate cancer.

PURPOSE OF REVIEW: Prostate cancer remains the most commonly diagnosed visceral cancer in men in the United States, with almost 200,000 newly diagnosed cases in 2003. Prevention of this disease would have a major impact on disease-associated cost, morbidity, and mortality for a large segment of the population. A major advance in prevention of prostate cancer came in 2003 with the publication of the Prostate Cancer Prevention Trial. This overview summarizes the results of that trial, the design of other large-scale trials, and advances in understanding of the molecular mechanisms underlying the effect of other promising agents. RECENT FINDINGS: The Prostate Cancer Prevention Trial demonstrated that use of finasteride is associated with a 25% reduction in the 7-year period prevalence of prostate cancer in men over age 55 years with normal digital rectal exam and initial prostate specific antigen <3.0 ng/ml. Use of finasteride was associated with a slightly higher risk of Gleason sum 7-10 tumors, some sexual side effects, and fewer urinary symptoms. A substantial body of new molecular evidence supports the existing body of clinical and epidemiological data leading to testing of vitamin E and selenium as preventative agents in men at risk for prostate cancer. Epidemiologic and molecular evidence also makes cyclooxygenase-2 inhibitors, lycopene, soy, and green tea promising agents. SUMMARY: Results of a population-based, randomized phase III trial demonstrates that finasteride can prevent prostate cancer. A large amount of data supports the use of other agents as potential preventatives, including selenium, vitamin E, vitamin D, other 5-alpha-reductase inhibitors, cyclooxygenase-2 inhibitors, lycopene, and green tea. Some of these agents are being tested in new large-scale phase III clinical trials.

Aged↗