Biomedical subjects
L H Klotz
Publications and source records attributed to L H Klotz.
Surveillance programs for early stage non-seminomatous testicular cancer: a practice guideline.
BACKGROUND AND PURPOSE: To identify an appropriate surveillance program for men with clinical stage I non-seminomatous germ cell tumors of the testis (NSGCT). MATERIALS AND METHODS: A systematic review of the published literature was combined with a consensus process, around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. RESULTS: No randomized controlled trials (RCTs) comparing surveillance schedules were found, but data from 12 case series and one RCT which compared radiotherapy with surveillance were reviewed. Variations in the schedules were not associated with observed variations in relapse, salvage, or survival rates. CONCLUSIONS: Men with clinical stage I testicular cancer, as defined by a normal physical examination, normal radiological scans (computed tomography [CT]) and serum markers (alpha-fetoprotein [AFP] and beta-subunit of human chorionic gonadotropin (betaHCG) which are normal or fall within normal limits during their expected half-lives, are eligible for surveillance. A recommended surveillance schedule is as follows: 1) Physical examination, blood serum marker tests (AFP and HCG), and chest x-rays should be conducted every month in the first year, every 2 months in the second year, every 3 months in the third year, and every 6 months in the fourth and fifth years; and 2) CT scans of the abdomen and pelvis should be conducted every 3 months in the first year, every 4 to 6 months in the second year and every 6 months in the third year, and once a year in the fourth and fifth year.
Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects.
PURPOSE: A prospective phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen (PSA) recurrence rates after radical prostatectomy. Our interim analysis includes secondary end points of differences in biochemistry, pathology and adverse events between the 2 groups. MATERIALS AND METHODS: Men with clinically confined prostate cancer were randomized to receive 7.5 mg. leuprolide intramuscularly monthly and 250 mg. flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy. Our study was powered to detect a 35% decrease in PSA recurrence, assuming a 30% recurrence rate in the 3-month arm after 3 years. RESULTS: A total of 547 men were randomized between August 1995 and April 1998. Men in the 8 and 3-month groups were equally stratified for T stage (29% T1c, 70% T2), Gleason grade (68% less than 4, 32% 4 or greater) and pretreatment PSA (63% less than 10, 27% 10 to 20 and 10% greater than 20 microg./l.). Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group (11.64 versus 9.95 microg./l., respectively, p = 0.0539). A total of 44 men withdrew from study before surgery and, therefore, were nonevaluable. Preoperative PSA nadir was less than 0.1 microg./l. in 43.3% versus 75.1% (p <0.0001), and 0.3 microg./l. or greater in 21% versus 9.2% after 3 versus 8 months, respectively (p <0.0006). Mean serum PSA decreased 98% to 0.12 microg./l. after 3 months, with a further 57% to 0.052 microg./l. from 3 to 8 months. Transrectal ultrasound determined that prostatic volume decreased 37% from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy (p = 0.0001) and a further 13% to 22.2 cc after 8 months (p = 0.03). Mean hemoglobin decreased 15% (148.2 to 125.4 gm./dl.) after 3-month neoadjuvant hormonal therapy but stabilized thereafter. Radical prostatectomy was completed in 500 men, while surgery was aborted intraoperatively in 3. Positive margin rates were significantly lower in the 8 than 3-month group (12% versus 23%, respectively, p = 0.0106). There were no fatal adverse events and no differences between the 2 groups in the severity or causality (p = 0.287, 0.0564) of adverse events, or incidence of increased liver enzymes or diarrhea (p = 0.691, 0.288, respectively). However, men in the 8-month group noticed a higher number of newly reported adverse events (4.5 versus 2.9, p <0.0001) and higher incidence of hot flushes than the 3-month group (87% versus 72%, respectively, p <0.0001). CONCLUSIONS: Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of neoadjuvant hormonal therapy, suggesting that the optimal duration of neoadjuvant hormonal therapy is longer than 3 months. Longer followup is needed to determine whether longer therapy alters PSA recurrence rates.
Canada's Medicare gets mediocre marks.
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Modernity, urology, and September 11.
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Bladder adenocarcinoma: 31 reported cases.
UNLABELLED: Retrospective review of 31 cases of bladder adenocarcinoma. METHODS: All patients diagnosed with adenocarcinoma of the bladder at the second affiliated hospital and commercial worker's hospital in Shanxi between 1985 and 1999 were reviewed. RESULTS: The cohort consisted of 31 patients, 25 with primary bladder adenocarcinoma, and 6 patients with urachal adenocarcinoma. Compared to the patients with primary adenocarcinoma, the urachal group were younger (67 versus 56 years), and more likely to be female (M:F 3:1 versus 1:2), and had a worse survival (45% versus 20% at 3 years). In the primary bladder adenocarcinoma group, the 3-year survival rate was 45% after radical cystectomy, and 33% after partial cystectomy. Local tumor recurrence after partial cystectomy was 25%. CONCLUSION: Urachal adenocarcinoma occurred in a younger age group with a female predominance compared to primary adenocarcinoma. Partial cystectomy was associated with a relatively high rate of local tumor recurrence.
The natural history of small renal masses.
PURPOSE: Ultrasound, computerized tomography and magnetic resonance imaging are widely available. Incidentally discovered small renal masses are reported more frequently. Most of these masses are low stage renal cell carcinomas. To understand better the natural history of these lesions and offer appropriate management, we followed prospectively a series of patients with this type of lesion. MATERIALS AND METHODS: A total of 13 patients with radiologically detected solitary small renal masses who were unfit for or refused surgery were followed with abdominal imaging for a median of 42 months. Median patient age was 69 years and mean lesion volume at diagnosis was 13.6 cm.3 or 2.95 cm. in diameter. Growth rate was calculated based on tumor volume rather than bi-dimensional diameter. Individual slopes of tumor size in time were calculated. RESULTS: Of the 13 patients 5 underwent surgery following a period of surveillance because of apparent tumor enlargement or new onset of symptoms. Pathological evaluation revealed renal cell carcinoma in all 5. No patient had metastases. Only 2 tumors were fast growing and these were the only 2 cases in which symptoms developed. When these patients were excluded from analysis, average growth rate was 1.32 cm.3 per year (p = 0.5, 95% confidence interval -3.00 to 5.76 cm.3 per year), which was not statistically significantly different from 0 slope or no growth. CONCLUSIONS: These results demonstrate that the growth rate of small renal tumors is variable, tumors that are destined to grow and possibly metastasize do so early and most small tumors grow at a low rate or not at all.
Intermittent androgen suppression for prostate cancer: Canadian Prospective Trial and related observations.
The Canadian Prospective Trial of intermittent androgen suppression was a prototype therapeutic initiative started in 1995 for the management of patients in biochemical relapse after radiation for localized prostate cancer. An interim analysis has yielded several observations on the relations between baseline serum prostate specific antigen (PSA), nadir serum PSA, Gleason score, and time off-treatment. In a typical androgen-dependent tumor, the response of serum PSA to androgen withdrawal is biphasic, but with early tumor progression, plateauing of serum PSA is observed. Ligand-independent activation of the androgen receptor, a mechanism subserving the initiation of androgen independence, can be counteracted experimentally with decoy molecules and clinically with nonsteroidal antiandrogens. In some patients, it is possible to lengthen the off-treatment interval by inhibiting the enzyme 5 alpha-reductase, an effect that can be reinforced by lowering serum testosterone with an antigonadotropin. Serial measurements of serum PSA indicate that intermittent androgen suppression engenders a more diverse range of hormone-related responses than previously appreciated. These include: (1) repeated differentiation of tumor with recovery of apoptotic potential; (2) inhibition of tumor growth by rapid restoration of serum testosterone; and (3) restraint of tumor growth by subnormal levels of serum testosterone. These responses are aspects of regulation that should be taken into account when planning long-term treatment of prostate cancer with intermittent androgen suppression.
Allopathic versus 'holistic' medicine.
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Urology as practiced in the Canadian Health Care System.
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The role of nutrition in prostate cancer prevention.
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Why is the rate of testicular cancer increasing?
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CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology Group.
OBJECTIVES: To test the hypothesis that neoadjuvant androgen ablation before radical prostatectomy reduces the likelihood of biochemical progression at 36 months. METHODS: Two hundred thirteen patients with localized prostate cancer were randomized to radical prostatectomy alone (Sx, n = 101) or a 12-week course of 300 mg of cyproterone acetate daily followed by surgery (CPA, n = 112). Biochemical progression (two consecutive detectable prostate-specific antigen [PSA] values) was determined for the entire group and by baseline PSA, Gleason score, clinical stage, and pathologic stage. RESULTS: The probability of biochemical progression at 36 months was similar in both groups (CPA 40.2%, Sx 30.1%; P = 0.3233). CPA patients with baseline serum PSA between 25 and 50 ng/mL had a lower probability of biochemical progression (CPA 63.5%, Sx 84.6%; P = 0.0038). No difference in the probability of biochemical progression was seen between groups when analyzed by clinical stage or Gleason score. When analyzed by pathologic margin status, no difference was observed in the probability of biochemical progression in patients with organ-confined disease (P = 0.4484). There was a trend for a higher probability of progression in the neoadjuvant arm in patients with positive and negative surgical margins (P = 0.0105, P = 0.0459; alpha = 0.005 with Bonferroni adjustment). CONCLUSIONS: Neoadjuvant androgen ablation with CPA reduces the positive margin rate significantly but does not result in a difference in biochemical progression at 3 years. This may be due to a lack of sufficient follow-up, insufficient power of the trial to demonstrate a small benefit, or a true lack of benefit of neoadjuvant androgen ablation before radical prostatectomy.
Prostate cancer: 1. The descriptive epidemiology in Canada.
A 70-year-old woman who experienced a long period of depression after her first husband's death from prostate cancer at the age of 63 has become increasingly anxious about her own health and that of her close family. A few years ago she married a man her own age; he is in good physical condition. Last year the family spent much of the winter in Florida, where the woman noticed several studies in the media suggesting that an epidemic of prostate cancer is occurring in North America and that because early detection can save lives men of retirement age should be checked by their physicians as soon as possible. In addition, 2 close friends recently diagnosed with prostate cancer. On his latest fishing trip her husband learned from a friend that 1 in 8 men get prostate cancer. He has not seen his family physician for several years, but his wife has booked an appointment for them to discuss their concerns.
Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.
BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS: Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment. RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52). CONCLUSIONS: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.