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John Trachtenberg

Publications and source records attributed to John Trachtenberg.

At least 37 records · Page 2Linked to original sources
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.

Aged↗
PubMed2004

Correlation of the primary Gleason pattern on prostate needle biopsy with clinico-pathological factors in Gleason 7 tumors.

OBJECTIVES: To correlate the primary Gleason pattern among patients with biopsy-derived Gleason 7 tumors with the radical prostatectomy specimen Gleason grading and other clinical and pathologic outcomes. METHODS AND MATERIALS: Among 474 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1997-2001, 205 (43%) had Gleason 7/10 tumors on pre-operative needle biopsy. Among theses patients, 148 (72.2%) were assigned a primary Gleason 3 pattern (3+4 = 7) and 57 (27.8%) were assigned a primary Gleason 4 pattern (4+3 = 7). The two groups were compared with respect to age, serum PSA levels, Gleason grade in the radical prostatectomy specimen, pathological stage and surgical margin status. RESULTS: Among patients with 3+4 tumors on needle biopsy, 64% remained primary Gleason grade 3 while 35% were up-graded to a primary pattern 4 following analysis of the radical prostatectomy specimen. Patients with 4+3 tumors on needle biopsy remained primary Gleason grade 4 in 51% of patients, while 49% of patients had their tumors down-graded to a primary 3 pattern (p = 0.09). There were no differences between patients with needle biopsy 3+4 and 4+3 patterns with respect to total Gleason score in the radical prostatectomy specimen (p = 0.42), pTNM stage (p = 0.36), extra-prostatic extension (p = 0.88), surgical margin involvement (p = 0.16), and seminal vesicle invasion (p = 0.19). In contrast, the primary Gleason pattern in the radical prostatectomy specimen correlated significantly with pTNM stage (p = 0.02) and seminal vesicle invasion (p= 0.003), but not with extra-prostatic extension (p = 0.32) and surgical margin involvement (p = 0.17). CONCLUSIONS: Among patients with Gleason 7 adenocarcinoma of the prostate, the biopsy-derived primary Gleason pattern does not appear to correlate with important clinical and pathologic outcomes. The utility of distinguishing a primary Gleason pattern on needle biopsy among patients with Gleason 7 tumors remains unclear given the limited and conflicting literature addressing this issue.

Adenocarcinoma↗
PubMed2003

Do older men benefit from curative therapy of localized prostate cancer?

PURPOSE: Prior decision-analytic models are based on outdated or suboptimal efficacy, patient preference, and comorbidity data. We estimated life expectancy (LE) and quality-adjusted life expectancy (QALE) associated with available treatments for localized prostate cancer in men aged >/= 65 years, adjusting for Gleason score, patient preferences, and comorbidity. METHODS: We evaluated three treatments, using a decision-analytic Markov model: radical prostatectomy (RP), external beam radiotherapy (EBRT), and watchful waiting (WW). Rates of treatment complications and pretreatment incontinence and impotence were derived from published studies. We estimated treatment efficacy using three data sources: cancer registry cohort data, pooled case series, and modern radiotherapy studies. Utilities were obtained from 141 prostate cancer patients and from published studies. RESULTS: For men with well-differentiated tumors and few comorbidities, potentially curative therapy (RP or EBRT) prolonged LE up to age 75 years but did not improve QALE at any age. For moderately differentiated cancers, potentially curative therapy resulted in LE and QALE gains up to age 75 years. For poorly differentiated disease, potentially curative therapy resulted in LE and QALE gains up to age 80 years. Benefits of potentially curative therapy were restricted to men with no worse than mild comorbidity. When cohort and pooled case series data were used, RP was preferred over EBRT in all groups but was comparable to modern radiotherapy. CONCLUSION: Potentially curative therapy results in significantly improved LE and QALE for older men with few comorbidities and moderately or poorly differentiated localized prostate cancer. Age should not be a barrier to treatment in this group.

Aged↗
PubMed2003

Single nucleotide polymorphism of the human kallikrein-2 gene highly correlates with serum human kallikrein-2 levels and in combination enhances prostate cancer detection.

PURPOSE: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk. PATIENTS AND METHODS: We studied 1,287 consecutive men who underwent prostate biopsies because of an abnormal prostate-specific antigen level. Serum and DNA were obtained before biopsy. Cases were patients with cancer, and controls were patients with no cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the T and C alleles, respectively. RESULTS: Of the 1,287 men, 616 had cancer, and 671 had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC, CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the genotypes, respectively (P =.0001). The adjusted odds ratios for prostate cancer for patients with the TT and CT genotypes compared with patients with the CC genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P =.004) and 1.51 (95% CI, 1.2 to 2.0; P =.002), respectively. The adjusted odds ratio for prostate cancer for patients in the fourth quartile of hK2 compared with the first quartile was 4.33 (95% CI, 2.9 to 6.4; P =.0001). When combined, the adjusted odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P =.0001) for patients with high hK2 levels and at least one T allele. CONCLUSION: The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.

Adenocarcinoma↗
PubMed2003

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma.

Mechanisms underlying prostate cancer (CaP) initiation and progression are poorly understood. A chromosomal instability mechanism leading to the generation of numerical and structural chromosomal changes has been implicated in the preneoplastic and neoplastic stages of CaP. Telomere dysfunction is one potential mechanism associated with the onset of such instability. To determine whether there was alteration in telomere length and chromosome number, 15 paraffin-embedded prostatectomy specimens were investigated using quantitative peptide nucleic acid (PNA) FISH analysis of representative foci of carcinoma, putative precancerous lesions (high-grade prostatic intraepithelial neoplasia, HPIN) and nondysplastic prostate epithelium. A significant decrease in telomere length was shown in both HPIN and CaP in comparison with normal epithelium. In addition, elevated rates of aneusomy suggested that increased levels of chromosomal aberrations were associated with decreased telomere length. Moreover, multiple foci of HPIN were shown to have a heterogeneous overall reduction of telomere length. This reduction was more evident in the histologic regions of the prostate containing CaP. Such observations lend support to the hypothesis that telomere erosion may be a consistent feature of CaP oncogenesis and may also be associated with the generation of chromosomal instability that characterizes this malignancy.

Adenocarcinoma↗
PubMed2003

A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer.

Preclinical studies demonstrate that intratumoral delivery of adenovirus expressing IL-2 eradicates pre-established tumors in mice and confers immune protection from rechallenge. To explore the activity of AdCAIL-2 in prostate cancer, a Phase I clinical trial was conducted in patients with localized disease and Gleason score >7 or prostate-specific antigen (PSA) >10 plus Gleason score 7. A total of 12 patients were injected 4 weeks prior to prostatectomy in a dose-escalation study at doses of 10(9), 5 x 10(9) and 10(10) PFU of virus. No dose-limiting toxicity was observed. Side effects included perineal discomfort, hematuria, flu-like symptoms in two patients and urinary hesitancy in one patient. Pathology demonstrated an inflammatory response consisting predominantly of CD3+CD8+ T lymphocytes with areas of tumor necrosis. Intracellular cytokine staining of tumor-infiltrating lymphocytes demonstrated increases in both gamma-interferon and IL-4 secreting T cells after vaccination. PSA levels fell in five of five evaluable patients treated at the lowest dose (mean decline of 33.3%, range 17-69%). At higher doses, PSA values initially increased after injection, then fell to baseline prior to surgery. This trial demonstrates the feasibility and safety of intraprostatic adenovector-mediated IL-2 gene delivery.

Adenoviridae↗
PubMed2003

Interstitial microwave thermal therapy for prostate cancer.

Thermal therapy is used to kill tumors by heating them to temperatures >50 degrees C for an extended period of time. Cell death results from thermal coagulation. The energy sources available for this approach include radiofrequency electrodes, microwave antennas, laser fiberoptics, and ultrasound transducers. Each of these modalities has the potential to be delivered in a minimally invasive manner, and many theoretical and experimental investigations of these devices have been performed. This review describes current knowledge of interstitial microwave thermal therapy for prostate cancer. Examples are given from an ongoing trial in patients who have recurrent or persistent disease following radiation therapy. Future directions for pretreatment planning and real-time monitoring and control are discussed. These techniques have the potential to optimize treatments on a patient-specific basis and will be instrumental in planned future trials of this therapy as first line for prostate cancer.

Animals↗
PubMed2003

Patient and community preferences for outcomes in prostate cancer: implications for clinical policy.

BACKGROUND: Preferences, or utilities, for health outcomes are central in prostate cancer decision-making. Utilities can be elicited directly from patients using standard techniques, or indirectly, using questionnaires that incorporate preference weights from community members. OBJECTIVES: To evaluate directly elicited and indirectly elicited (questionnaire-derived, community-weighted) utilities for prostate cancer outcomes and the effects of sexual, urinary, and bowel dysfunction on them. MATERIALS AND METHODS: Utilities for the current health of 141 prostate cancer patients, recruited from ambulatory clinics, were elicited directly with the Patient Oriented Prostate Utility Scale, rating scale (PORPUS-U(RS)) and standard gamble (PORPUS-U(SG)) subscales. Patients completed the Health Utilities Index (HUI) and Quality of Well Being Scale (QWB), utility instruments incorporating community preferences, and the UCLA Prostate Cancer Index. RESULTS: Patients' treatments included radical prostatectomy (18%), radiation (60%), and hormonal (42%). Mean utility scores for current health were 0.65 (QWB), 0.79 (PORPUS-U(RS)), 0.80 (HUI), 0.86 (PORPUS-U(SG)). Utility decrements for dysfunction were small (0.08-0.14 [sexual], 0.06 to 0.13 [urinary], and 0.01 to 0.13 [bowel]), and even smaller when adjusted for concomitant changes in other quality of life (QOL) domains. CONCLUSIONS: Patients' directly elicited utilities for their own health were higher than community-derived utilities obtained from HUI and QWB administration to the same patients. HUI scores of these patients were similar to those of age-matched Canadian men. Sexual, urinary, and bowel problems were common but had less impact on overall QOL than reported in previous utility studies. These results weaken the argument that prostate cancer screening and treatment should be limited because of severe and debilitative side effects.

Age Factors↗
PubMed2003

Delay in surgical therapy for clinically localized prostate cancer and biochemical recurrence after radical prostatectomy.

BACKGROUND: In Canada, waiting times for cancer care have been increasing, particularly for patients with genitourinary malignancies. We examined whether delay from diagnosis for patients undergoing surgery for clinically localized prostate cancer affects cancer cure rates. METHODS: We conducted a historical cohort study among 645 patients who underwent radical prostatectomy between 1987 and 1997, using biochemical recurrence (PSA elevation) and metastasis as endpoints. We examined whether patients who underwent surgery >/= months (delayed surgery group) from the date of diagnosis had reduced recurrence-free survival, compared to patients who had surgery <3 months (early surgery group) from the date of diagnosis, adjusting for grade, stage and PSA level at diagnosis. RESULTS: The crude 10-year recurrence-free and metastasis-free survival rates for all patients were 71.1% (95% C.I.: 64.9% - 77.3%) and 95.3% (95% C.I.: 91.3% - 99.3%), respectively. Of the 645 patients, 189 (29.3%) had surgery >/= months after diagnosis. The median time from the date of diagnosis to surgery was 68 days (range 15 to 951 days). The 10-year recurrence-free survival was higher for patients who underwent early surgery (74.6%, 95% C.I.: 67.9% - 81.4%) compared to patients in the delayed surgery group (61.3%, 95% C.I.: 46.7% - 76.0%, p=0.05). The crude and adjusted hazard ratios for developing biochemical recurrence for patients in the delayed surgery group were 1.58 (95% C.I.: 1.0 - 2.4, p=0.04) and 1.46 (95% C.I.: 0.9 - 2.3, p=0.09), respectively, compared to patients who underwent early surgery. CONCLUSIONS: There may exist a possible relationship between delays from diagnosis for radical prostatectomy and prostate cancer cure rates. These findings may have many biases that could not be properly accounted in this retrospective analysis and larger cohort analyses will be required to confirm these findings.

Adult↗
PubMed2003

Comprehensive assessment of candidate genes and serological markers for the detection of prostate cancer.

We examined whether selected polymorphisms in 11 candidate genes and serum levels of insulin-like growth factor I (IGF-I) help predict the presence of prostate cancer among patients prescreened with prostate-specific antigen (PSA) and digital rectal exam (DRE). We studied 1031 consecutive men who underwent one or more prostate biopsies because of an elevated PSA level (>4 ng/ml) or an abnormal DRE. Eleven candidate genes were examined, including the androgen receptor, SRD5A2, CYP17, CYP3A4, vitamin D receptor, PSA, GST-T1, GST-M1, GST-P1, IGF-I, and IGF binding protein 3. We also measured serum IGF-I levels before biopsy. Of the 1031 men, 483 had cancer on any biopsy (cases) and 548 men had no cancer (controls). Age, ethnicity, total PSA, and DRE result were strongly predictive of the presence of prostate cancer. The mean IGF-I level for cases (119.4 ng/ml) was lower than for controls (124.4 ng/ml, P = 0.05) and were not predictive for the presence of prostate cancer. We found no associations between the androgen receptor, SRD5A2, CYP17, CYP3A4, vitamin D receptor, GST-M1, GST-P1, and IGF binding protein 3 genotypes and prostate cancer risk. The adjusted odds ratios for having prostate cancer for patients with the GST-T1 and IGF-I variant alleles were 1.64 (95% confidence interval, 1.1-2.4; P = 0.01) and 1.70 (95% confidence interval, 1.1-2.7; P = 0.02), respectively. Nine of 11 candidate genes were not significantly predictive for prostate cancer in a clinical setting. The GST-T1 and IGF-I polymorphisms demonstrated modest associations with prostate cancer risk. IGF-I levels were not helpful in identifying patients with prostate cancer at the time of biopsy.

Adult↗
PubMed2002

A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer.

PURPOSE: We compared the endocrinological and biochemical efficacy of abarelix depot, a gonadotropin-releasing hormone antagonist, with that of a widely used combination of luteinizing hormone releasing hormone agonist and a nonsteroidal antiandrogen. MATERIALS AND METHODS: A total of 255 patients were randomized to receive open label 100 mg. abarelix depot or 7.5 mg. leuprolide acetate intramuscularly injection on days 1, 29, 57, 85, 113 and 141 for 24 weeks. Patients in the abarelix group received an additional injection on day 15 and those in the leuprolide acetate group received 50 mg. bicalutamide daily. Patients could continue treatment with study drug for an additional 28 weeks. The efficacy end points were the comparative rates of avoidance of testosterone surge (greater than 10% increase) within 7 days of the first injection and the rapidity of achieving reduction of serum testosterone to castrate levels (50 ng./dl. or less) on day 8. Patients were monitored for adverse events and laboratory abnormalities. RESULTS: Abarelix was more effective in avoidance of testosterone surge (p <0.001) and the rapidity of reduction of testosterone to castrate levels on day 8 (p <0.001) than combination therapy. No significant difference was seen between the groups in the initial rate of decline of serum prostate specific antigen or the ability to achieve and maintain castrate levels of testosterone. No unusual or unexpected adverse events were reported. CONCLUSIONS: Abarelix as monotherapy achieves medical castration significantly more rapidly than combination therapy and avoids the testosterone surge characteristic of agonist therapy. Both treatments were equally effective in reducing serum prostate specific antigen, and achieving and maintaining castrate levels of testosterone.

Aged↗
PubMed2002

The uncertainty of radio frequency treatment of renal cell carcinoma: findings at immediate and delayed nephrectomy.

PURPOSE: Radio frequency thermal therapy for the ablation of renal cell carcinoma has been reported. Outcomes are usually measured by imaging alone. We have performed ex vivo and in vivo experiments using radio frequency in porcine models in our laboratory. We now report our early experience in the treatment of renal cell carcinoma in patients who underwent post-radio frequency radical or partial nephrectomy. MATERIALS AND METHODS: We treated 10 patients diagnosed with small renal masses with radio frequency. All masses were biopsied before treatment. In 4 patients 5 renal cell carcinomas were treated with radio frequency after surgical exposure of the tumor followed immediately by partial or radical nephrectomy (acute group). Six other patients were treated percutaneously with ultrasound or computerized tomography guided radio frequency under local anesthesia and intravenous sedation 7 days before partial or radical nephrectomy (delayed group). A median of 2 radio frequency cycles was applied. Mean total heating time was 17 minutes 15 seconds. Specimens were analyzed grossly and histologically. Triphasic contrast-enhanced computerized tomography and/or magnetic resonance imaging was performed before and 7 days after radio frequency treatment in the delayed group. RESULTS: Mean radiological largest diameter of all 11 masses was 2.4 cm. and mean gross diameter was 2.2 cm. Pathological examination demonstrated residual viable tumor in approximately 5% of the volume in 4 of the 5 tumors in the acute group and in 3 of the 6 masses of the delayed group. In 1 delayed case the viable tumor appeared to be in contact with the renal vein. No significant complications were observed in 9 of the 10 patients. In 1 delayed case, a subcapsular hepatic hematoma, biliary fistula and pneumonia developed and resolved. CONCLUSIONS: Based on our experience, we continue to consider percutaneous radio frequency for the treatment of small renal cell carcinomas as a potentially curative therapy. However, complete tumor cell death appears to be difficult to achieve with our current treatment protocol. More phase II testing is indicated to ensure that this technique is an effective and reproducible treatment alternative.

Carcinoma, Renal Cell↗
PubMed1999

Patient-reported outcomes following radical prostatectomy.

The present study was designed to assess disease-specific outcome measures of impotence, incontinence and stricture disease after radical prostatectomy through an anonymous patient self-reported questionnaire. Recent studies suggest complications reported anonymously by patients are higher than previously reported. The aim is to provide clinicians with site-specific patient information which may be of benefit in pre-operative and postoperative patient encounters. Patient self-reported incidence of postoperative impotence (82.2%) and ongoing incontinence (59.3%) was high but consistent with several published reports.3-12,21 The patient self-reported incidence of stricture (15.2%) was low.

Journal Article↗
PubMed1998

Alpha-blocker therapy for benign prostatic hyperplasia: a comparative review.

In the past decade there has been a shift in the primary approach to therapy for BPH, from surgical intervention to pharmacotherapy. Therapies with alpha-blockers, particularly long-acting selective alpha1-adrenoreceptor antagonists, has proven effective, and hence has become a popular treatment option. In randomized controlled trials, 3 alpha-adrenoreceptor antagonists -terazosin, doxazosin, and tamsulosin -have been shown to significantly improve both the mean peak urinary flow and the severity of BPH-related symptoms. There are no currently published trials comparing the clinical efficacy of these drugs. Reports from non-comparative trials suggest that the effects on symptoms and flow rates are similar. However, side effects, such as postural hypotension, asthenia, and dizziness may be less with tamsulosin. Use of tamsulosin is associated with loss of ejaculation in 4.5% of men. Until differences in efficacy are demonstrated, the choice of alpha-blocker will depend on tolerance for side effects and convenience of administration.

Journal Article↗
PubMed1997

A review of hormonal treatment in advanced prostate cancer.

In the treatment of advanced prostate cancer, androgen ablation has proven to be the cornerstone. Several important questions about its use, however, remain unanswered. The first question is whether androgen ablation should be started at the time of diagnosis, or when symptoms arise. Although previous evidence had suggested no benefit to early therapy, a recent large trial of patients has shown clear benefit. Patients with locally advanced and asymptomatic metastatic disease were randomly assigned to early treatment, or treatment started at signs of progression: the early treatment group showed benefit in time to progression, incidence of severe complications, and time to death. The other major unresolved issue is the type of androgen ablation to be used. Maximal androgen blockade (MAB) has been shown to increase the survival of patients with metastatic disease in a least two large, well-conducted trial, although other trials have contradicted this finding. A recent meta-analysis of 22 MAB trials containing more than 5000 patients has suggested that MAB does not prolong life. A large trial by the National Cancer Institute (NCI) NCI INT-0105, from which preliminary results are now available, has shown that castration and an antiandrogen is no better than castration alone in terms of time to progression and survival. This trial, furthermore, did not find that MAB was superior in low-volume, good-performance status patients. Androgen ablation is not a cure for advanced prostate cancer, but it does provide excellent palliation. New treatment regimens, and new studies, are needed to optimize treatment for these men.

Journal Article↗
PubMed1996

An assessment of CME needs of Canadian urologists.

The Canadian Urological Association has recently developed a new continuing medical education vehicle, Video Journal in Urology. The editorial content of this quarterly production is determined by the results of a needs assessment, the results of which are described in this paper. The needs assessment, as a two-page questionnaire, was mailed to 504 urologists. One hundred and eight-three responded, a response rate of 36.3%. The topic areas ranked as most interesting were largely centered around the broad topic of prostate cancer.

Journal Article↗