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Laurence Klotz

Publications and source records attributed to Laurence Klotz.

At least 19 recordsLinked to original sources
PubMed2026

Optimizing prostate biopsy decision making - (MUSIC-screen): A 1:1 randomized controlled trial comparing micro-ultrasound versus multiparametric magnetic resonance imaging for prostate cancer diagnosis.

BACKGROUND: Micro-ultrasound (microUS) represents a potential alternative to multiparametric magnetic resonance (mpMRI) in guiding prostate biopsy, with level 1 evidence demonstrating non-inferiority to detect Grade Group &#x2265;2 (GG&#xa0;&#x2265;&#xa0;2) prostate cancer in biopsy-na&#xef;ve men. However, a critical gap remains in the screening pathway, in which imaging is needed to identify men at risk and determine whether biopsy is warranted. METHODS: MUSIC-Screen is a phase 3, open-label, noninferiority 1:1 randomized controlled trial evaluating microUS as an alternative imaging compared to mpMRI for determining the need for prostate biopsy in biopsy- and imaging- na&#xef;ve men at risk for GG&#xa0;&#x2265;&#xa0;2. A total of 1284 men will be randomized to undergo either microUS or mpMRI. Men with PRI-MUS 3-5 or PI-RADS 3-5 lesion will undergo targeted and systematic biopsy. Men with negative imaging and PSA density&#xa0;&#x2265;&#xa0;0.15 will undergo systematic biopsy, while those with PSA density&#xa0;<&#xa0;0.15 will defer biopsy. RESULTS: The primary outcome is GG&#xa0;&#x2265;&#xa0;2 detection in each study arm. The primary hypothesis is that microUS is non-inferior to mpMRI for screening and detection of GG&#xa0;&#x2265;&#xa0;2. Secondary objectives include comparison of GG&#xa0;&#x2265;&#xa0;2 detection rates in targeted cores among patients with PRI-MUS or PI-RADS scores of 3-5, proportion of men who defer biopsy but are diagnosed with GG&#xa0;&#x2265;&#xa0;2 within 8&#xa0;years, assessment of the negative predictive value of each imaging modality, and health economic analyses. CONCLUSION: MUSIC-Screen will determine whether microUS can be used as an imaging modality to inform biopsy decision making that is non-inferior to mpMRI for GG&#xa0;&#x2265;&#xa0;2 prostate cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06626022.

Humans↗
PubMed2006

A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.

OBJECTIVES: This study compared the complications and the cancer control of elective nephron-sparing surgery (NSS) and radical nephrectomy (RN) in patients with a small (<or=5 cm), solitary, low-stage N0 M0 tumour suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney. METHODS: 541 patients were randomised in a prospective, multicentre, phase 3 trial to undergo NSS (n=268) or RN (n=273) together with a limited lymph node dissection. RESULTS: This publication reports only on the complications reported for both surgical methods. The rate of perioperative blood loss<0.5l was slightly higher after RN (96.0% vs. 87.2%) and the rate of severe haemorrhage was slightly higher after NSS (3.1% vs. 1.2%). Ten patients (4.4%), all of whom were treated with NSS, developed urinary fistulas. Pleural damage (11.5% for NSS vs. 9.3% for RN) and spleen damage (0.4% for NSS and 0.4% for RN) were observed with similar rates in both groups. Postoperative computed tomography scanning abnormalities were seen in 5.8% of NSS and 2.0% of RN patients. Reoperation for complications was necessary in 4.4% of NSS and 2.4% of RN patients. CONCLUSIONS: NSS for small, easily resectable, incidentally discovered RCC in the presence of a normal contralateral kidney can be performed safely with slightly higher complication rates than after RN. The oncologic results are eagerly awaited to confirm that NSS is an acceptable approach for small asymptomatic RCC.

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PubMed2006

Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer: clinical parameters.

BACKGROUND: This prospective Phase II study was undertaken to evaluate intermittent androgen suppression as a form of therapy in men with localized prostate cancer who failed after they received external beam irradiation. METHODS: Patients who demonstrated a rising serum prostate-specific antigen (PSA) level after they received radiotherapy and who were without evidence of distant metastasis were accepted into the study. Treatment in each cycle consisted of cyproterone acetate given as lead-in therapy for 4 weeks, followed by a combination of leuprolide acetate and cyproterone acetate, which ended after a total of 36 weeks. RESULTS: Of 109 patients registered, 103 patients were eligible for interruption of treatment, yielding a PSA response rate of 95%. The study continued for 6 years with a mean follow-up of 3.7 years (median follow-up, 4.2 years). The time off treatment averaged 53% of the total cycle time but, in absolute terms, decreased with each succeeding cycle, ranging from 63.7 weeks in Cycle 1 to 25.6 weeks in Cycle 5. Prostate volume was reduced by 40% in Cycle 1 and by 34% in Cycle 2, and there were no decreases in Cycle 3 or Cycle 4. At the end of the trial, 38.5% of patients still were receiving treatment, 23.9% of patients had failed, and 15.6% of patients had died. Only 2% of deaths were cancer-specific. CONCLUSIONS: Biochemical recurrence after irradiation for localized prostate cancer was amenable to cyclic androgen withdrawal therapy and showed a high response rate. Despite progressively shorter treatment cycles, the off-treatment interval remained appreciable, ranging from 65% in Cycle 1 to 46% in Cycle 5.

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PubMed2006

Active surveillance versus radical treatment for favorable-risk localized prostate cancer.

Widespread prostate-specific antigen (PSA) screening in North America has resulted in a profound stage migration and a marked increase in incidence. One in six men is now diagnosed, many with small-volume, low-grade cancer. This incidence is dramatically higher than the 3% lifetime risk of prostate cancer death that characterized the pre-screening era. This article summarizes the case for active surveillance for "favorable-risk" prostate cancer with selective delayed intervention for rapid biochemical progression, assessed by increasing PSA levels, or grade progression. The results of a large phase II trial using this approach are reviewed. To date, this study has shown that virtually all men with favorable-risk prostate cancer managed in this fashion will die of unrelated causes. Based on the Swedish randomized trial of radical prostatectomy versus watchful waiting, the Connecticut observation series, and the Toronto active surveillance experience, a number needed to treat analysis of the benefit of radical treatment of all newly diagnosed favorable-risk prostate cancer patients, compared with a strategy of active surveillance with selective delayed intervention, is presented. This suggests that approximately 73 patients will require radical treatment for each prostate cancer death averted. This translates into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in favorable-risk disease. The approach of active surveillance with selective delayed intervention based on PSA doubling time and repeat biopsy represents a practical compromise between radical therapy for all patients (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).

Disease Progression↗
PubMed2006

Modeling prostate specific antigen kinetics in patients on active surveillance.

PURPOSE: Prostate specific antigen doubling time was used to stratify patients into groups at low and high risk for progression. The prostate specific antigen kinetics in these 2 groups were modeled. MATERIALS AND METHODS: In this prospective, single-arm cohort study patients with favorable clinical parameters (stage T1b-T2b N0M0, Gleason score 7 or less, prostate specific antigen 15 ng/ml or less) were conservatively treated with watchful waiting. Evolution of serial prostate specific antigen measurements over time was estimated from a general linear mixed model of the natural log of prostate specific antigen. The corresponding average and individual prostate specific antigen doubling times were also calculated. RESULTS: Since November 1995 a total of 231 patients had at least 6 months of followup and at least 3 prostate specific antigen measurements. Based on prostate specific antigen doubling time and repeat biopsy, 93 patients fulfilled the criteria for high risk of disease progression and 138 were defined as low risk. Given the baseline status of these individuals, 2 reference average lines (high risk and low risk) were derived to model the evolution of prostate specific antigen levels and permit more rational decision making regarding the need for definitive intervention. The average prostate specific antigen doubling time was 2.97 years (95% CI 2.2-4.4) in patients allocated to the high risk group and 6.54 years (95% CI 4.8-12.3) in those at low risk. CONCLUSIONS: By applying the dynamic prognostic rule in combination with serial biopsy, a rational decision for definitive intervention based on the risk of disease progression could be optimally recommended about 2.3 years after initiated surveillance.

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PubMed2006

Combined androgen blockade: an update.

The use of combined androgen blockade therapy in prostate cancer management remains controversial. This article reviews the effect of the different non-steroid androgens in blocking androgen-independent activation of the androgen receptor in the androgen-depleted environment, and the potential benefit of bicalutamide in comparison to the first generation of anti-androgens (flutamide and nilutamide). An estimate of the benefit of combined therapy with bicalutamide suggests there is a high probability that bicalutamide 50 mg as combined therapy provides a survival advantage over castration alone. This treatment must be balanced against the potential for an increase in side-effects and a consequent adverse effect on the patient's quality of life.

Androgen Antagonists↗
PubMed2005

Active surveillance for prostate cancer: for whom?

Prostate-specific antigen (PSA) -based prostate cancer screening results in the diagnosis of prostate cancer in many men who are not destined to have clinical progression during their lifetime. Good-risk prostate cancer, defined as a Gleason score of 6 or less, PSA < 10, and T1c to T2a, now constitutes 50% of newly diagnosed prostate cancer. In most of these patients, the disease is indolent and slow growing. The challenge is to identify those patients who are unlikely to experience significant progression while offering radical therapy to those who are at risk. The approach to favorable-risk prostate cancer described in this article uses estimation of PSA doubling time (PSA DT) to stratify patients according to the risk of progression. Patients who select this approach are managed initially with active surveillance. Those who have a PSA DT of 3 years or less (based on a minimum of three determinations over 6 months) are offered radical intervention. The remainder are closely monitored with serial PSA and periodic prostate rebiopsies (at 2, 5, and 10 years). In this series of 299 patients, the median DT was 7 years. Forty-two percent had a PSA DT > 10 years, and 20% had a PSA DT > 100 years. The majority of patients on this study remain under surveillance. The approach of active surveillance with selective delayed intervention based on PSA DT represents a practical compromise between radical therapy for all (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).

Biomarkers, Tumor↗
PubMed2005

Active surveillance with selective delayed intervention using PSA doubling time for good risk prostate cancer.

Good risk prostate cancer, defined as patients with a Gleason score of 6 or less, PSA<10-15, and T1c-T2a, now constitutes 50% of newly diagnosed prostate cancer. For most of these patients, the disease is indolent and slow growing. There is substantial evidence that it does not pose a threat during the lifetime of most patients. The challenge is to identify those patients who are not likely to experience significant progression while offering radical therapy to those who are at risk. To date, molecular markers have failed to provide sufficiently reliable predictive information to influence decision making. The approach to favorable risk prostate cancer described in this article uses estimation of PSA doubling time (PSA DT) to stratify patients according to the risk of progression. Patients who select this approach are managed initially with active surveillance. those who have a PSA DT of 3 years or less (based on a minimum of 3 determinations over 6 months) are offered radical intervention. The remainder are closely monitored with serial PSA and periodic prostate re-biopsies (at 2, 5, and 10 years). In this series of 299 patients, the median doubling time was 7.0 years. 42% had a PSA DT>10 years, and 20% had a PSA DT>100 years. The majority of patients in this study remain on surveillance. The approach of active surveillance with selective delayed intervention based on PSA DT represents a practical compromise between radical therapy for all (which results in overtreatment for patients with indolent disease), and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).

Humans↗
PubMed2005

Active surveillance with selective delayed intervention is the way to manage 'good-risk' prostate cancer.

This review summarizes the case for active surveillance of 'good-risk' prostate cancer, with selective delayed intervention for rapid biochemical progression, assessed by rising prostate-specific antigen (PSA) levels or grade progression. The results of a large phase II trial using this approach are also reviewed. A prospective phase II study of active surveillance with selective delayed intervention was initiated in 1995. Patients were managed initially with surveillance; those who had a PSA doubling time (PSADT) of < or = 2 years, or grade progression on repeat biopsy, were offered radical intervention. The remaining patients were closely monitored. The cohort now consists of 299 patients with good-risk--or, in men over 70 years of age, intermediate-risk--prostate cancer. The median PSADT was 7 years, 42% had a PSADT > 10 years. The majority of patients remain on surveillance. At 8 years, overall actuarial survival was 85%, and disease-specific survival was 99%. To date, this study has shown that most men with 'good-risk' prostate cancer will die of unrelated causes. The approach of active surveillance with selective delayed intervention based on PSADT represents a practical compromise between radical therapy for all patients, which results in overtreatment for patients with indolent disease, and watchful waiting with palliative therapy only, which results in undertreatment for those with aggressive disease. The results at 8 years were favorable. Longer follow-up will be required if the study is to confirm the safety of this approach in men with a long life expectancy (> 15 years).

Follow-Up Studies↗
PubMed2005

Combined androgen blockade: the case for bicalutamide.

Combination therapy consists of castration plus an antiandrogen. Following medical or surgical castration, the androgen receptor can be activated by adrenal androgens, low levels of residual testosterone, and ligand-independent activators. The survival benefit of combination therapy compared with castration alone is one of the most studied questions in urology. Results from trials comparing combination therapy to castration alone are variable. A metaanalysis of 26 randomized trials indicated that the type of antiandrogen used is relevant. Combination therapy using nonsteroidal antiandrogens was associated with a statistically significant overall survival benefit. In contrast, combination therapy using steroidal antiandrogens was associated with reduced survival compared with castration alone. Bicalutamide 50 mg has a number of advantages compared with nilutamide and flutamide when used in combination with castration. These include an improved side-effect profile, once-daily dosing, more potent inhibition of androgen-independent activation of the androgen receptor through favorable interactions with nuclear coactivators and corepressors, and evidence for improved survival in one randomized trial. An analysis combining historic trial data suggests that bicalutamide 50 mg in addition to androgen deprivation may reduce the hazard ratio (HR) for prostate cancer mortality by 20% (HR, 0.80; 95% CI, 0.66-0.98).

Androgen Antagonists↗
PubMed2004

Dietary fat and prostate cancer.

PURPOSE: Data from histopathological and migratory studies suggest that 1 or more late stage environmental promoters are involved in the development of clinical carcinoma of the prostate. Laboratory investigations and variously designed epidemiological studies in man have suggested that dietary fat may be one of these candidate tumor promoters but other studies have questioned this association. The biologically plausible associations that have been hypothesized include total energy consumption, altered androgen metabolism, oxidative stress, specific fatty acid consumption and pesticide intake. We provide a critical appraisal of the existing evidence for an association between dietary fat consumption and prostate cancer, and review the biologically plausible relationships. MATERIALS AND METHODS: All 33 published case-control and cohort studies that examined the relationship between prostate cancer and dietary fat or specific fatty food types were critically appraised. Eight studies suggested a statistically significant association, and many studies noted significant associations for specific types of fatty foods (eg milk or meat) and prostate cancer. RESULTS: In light of the inherent biases in the methodology of studying dietary fat intake and carcinoma of the prostate, we conclude that the evidence is consistent. CONCLUSIONS: Corroborative studies in humans are required to better define this relationship. Prospective studies of dietary intervention should be encouraged.

Androgens↗
PubMed2004

Active surveillance with selective delayed intervention: using natural history to guide treatment in good risk prostate cancer.

PURPOSE: This article reviews the data supporting an approach of active surveillance with selective delayed intervention for good risk localized prostate cancer. The challenge is to identify those patients who are not likely to experience significant progression, while offering radical therapy to those who are at risk. MATERIALS AND METHODS: A prospective phase 2 study of active surveillance with selective delayed intervention was initiated in 1995. Patients were treated initially with surveillance, while those who had a prostate specific antigen (PSA) doubling time (DT) of 2 years or less, or grade progression on re-biopsy were offered radical intervention. The remainder were closely monitored. RESULTS: The cohort consisted of 299 patients with good risk prostate cancer or intermediate risk prostate cancer in men older than 70 years. Median PSA DT was 7.0 years and 35% of the men had a PSA DT of greater than 10 years. The majority of patients remain on surveillance. At 8 years overall actuarial survival was 85% and disease specific survival was 99%. CONCLUSIONS: Most men with favorable risk prostate cancer will die of unrelated causes. The approach of active surveillance with selective delayed intervention based on PSA DT represents a practical compromise between radical therapy in all, which results in overtreatment in patients with indolent disease, and watchful waiting with palliative therapy only, which results in under treatment in those with aggressive disease. Results at 8 years are favorable. Longer followup will be required to confirm the safety of this approach in men with long (greater than 15-year) life expectancy.

Disease Progression↗
PubMed2004

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

OBJECTIVE: To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. PATIENTS AND METHODS: A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. RESULTS: As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. CONCLUSIONS: The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

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PubMed2004

Variation in patterns of practice in diagnosing screen-detected prostate cancer.

OBJECTIVE: To determine the practice pattern of repeat prostate biopsies to detect prostate cancer, as there is growing evidence to support the recommendation that a repeat prostate biopsy should be taken after an initially negative prostate biopsy, the rate of cancer detection then being approximately 30%. PATIENTS AND METHODS: We examined the practice patterns of taking a repeat prostate biopsy after an initial negative biopsy and the predictors for cancer at repeat biopsy among 1536 patients who had an initial prostate biopsy because of an elevated prostate-specific antigen (PSA) level (>4.0 ng/mL) or abnormal digital rectal examination. RESULTS: Of the 1536 men, 712 (46.4%) had cancer detected on the first biopsy; of the remaining 824 with no cancer detected, 268 (32.5%) had a repeat biopsy within a year, and 68 of these (25.4%) had cancer detected. Of the cancers detected at repeat biopsy, 31% were high-grade. Men with abnormal histology (prostatic intraepithelial neoplasia or atypia) had an odds ratio of 3.2 (P < 0.001) for having a repeat biopsy. For men with normal initial prostate histology, those with an initial PSA of 10.0-20.0 and >20.0 ng/mL had an odds ratio of 3.6 and 4.5 (both P < 0.001), respectively, for a repeat prostate biopsy, compared with patients with a PSA of <10.0 ng/mL. However, the PSA level was not predictive of prostate cancer at repeat biopsy, but age and prostate volume were. CONCLUSIONS: A third of patients had a repeat biopsy after a negative biopsy. The most important factors influencing whether a patient was to have a repeat biopsy were initial biopsy histology and PSA level. However, the latter was not an important factor for predicting prostate cancer at repeat biopsy.

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