Biomedical subjects
G W Chodak
Publications and source records attributed to G W Chodak.
Improved detection of recurrent bladder cancer using the Bard BTA stat Test.
OBJECTIVES: To evaluate the BTA stat Test in the detection of recurrent bladder cancer. METHODS: Sensitivity and specificity were determined using frozen voided urine samples from patients with recurrent bladder cancer, volunteers, patients with nonurologic conditions, and patients with a history of bladder cancer but free of disease. Results of cytology and the original BTA Test were compared with the sensitivity of the BTA stat Test in a large subgroup of the patients with cancer. RESULTS: The BTA stat Test detected 147 (67%) of 220 recurrent cancers. For those urine samples with previous cytologic and BTA Test results available, cytology had a sensitivity of 23%, the BTA Test 44%, and the BTA stat Test 58% for detection of recurrent cancer (P < 0.001, stat versus cytology). The specificity of the BTA stat Test was 72% for benign genitourinary disease and 95% in healthy volunteers. CONCLUSIONS: The BTA stat Test has high sensitivity and is significantly superior to voided urine cytologic analysis in the detection of recurrent bladder cancer.
Results of radical prostatectomy in men with locally advanced prostate cancer: multi-institutional pooled analysis.
OBJECTIVE: We investigated the disease-specific and metastasis-free survival rates in men with locally advanced (clinical stage T3) prostate cancer who were treated surgically. METHODS: A retrospective, multi-institutional pooled analysis of the results of surgical treatment in 345 men with clinical stage T3 disease was performed. Survival curves were generated using the Kaplan-Meier method. RESULTS: Among 298 evaluable patients, pelvic lymphadenectomy alone was performed in 56 men (19%), while 242 men (81%) underwent node dissection and radical prostatectomy. In total, 122 of 298 patients (41%) had nodal metastases and/or seminal vesicle tumor spread. Pathologically organ-confined disease was noted in 27 men (9%). The actuarial 10-year disease-specific and metastasis-free survival rates for all patients managed surgically were 57 and 32%, respectively. For patients with well, moderately and poorly differentiated tumors, cancer-specific survival rates at 10 years were 73, 67 and 29%, respectively. CONCLUSIONS: A large number of men with clinical stage T3 prostate cancer have advanced disease and are unlikely to achieve improved long-term survival with surgery alone. Although there may be a role for radical prostatectomy in selected patients with low to intermediate grade tumors, such treatment appears unlikely to result in long-term survival in men with high grade disease. A prospective study is necessary to determine the optimal treatment approach in men with locally advanced prostate cancer.
Bicalutamide-associated fulminant hepatic failure.
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Results of radical prostatectomy in men with clinically localized prostate cancer.
OBJECTIVE: To assess the results of radical prostatectomy in men with early prostate cancer. DESIGN: Retrospective, nonrandomized, multi-institutional pooled analysis. SETTING: Eight university medical centers in the United States and Europe. PATIENTS: A total of 2758 men with stage Tl and T2 prostatic cancer. MAIN OUTCOME MEASURES: Disease-specific and metastasis-free survival rates. RESULTS: Tumor grade was the most important preoperative factor in determining outcome. Disease-specific survival 10 years following surgery and associated 95% confidence intervals were 94% (range, 87%-98%), 80% (range, 74%-85%), and 77% (range, 65%-86%) for those men with grade 1, 2, and 3 tumors, respectively. Metastasis-free survival at 10 years was 87% (range, 78%-92%), 68% (range, 62%-73%), and 52% (range, 38%-64%) for patients with grade 1, 2, and 3 cancers, respectively. CONCLUSIONS: Radical prostatectomy leads to high 10-year disease-specific survival rates in men with all tumor grades. However, caution is needed in comparing these results with similar studies of alternative treatment strategies, such as watchful waiting, due to the inherent potential biases in uncontrolled trials. Nevertheless, these results offer the best currently available estimates of 10-year outcome of radical prostatectomy in men with clinically localized prostate cancer and may be useful in counseling patients with early malignancy.
Additional therapy after prostatectomy: implications for patient counseling.
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Re: Long-term survival and mortality in prostate cancer treated with noncurative intent.
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Bicalutamide in the treatment of advanced prostatic carcinoma: a phase II multicenter trial.
OBJECTIVES: The safety, efficacy, and pharmacokinetics of the nonsteroidal antiandrogen bicalutamide were investigated in a Phase II trial in 150 patients with metastatic prostate cancer. METHODS: Patients took bicalutamide, 50 mg daily, in an open-label multicenter North American trial. RESULTS: The objective response rate (modified European Organization on Research and Treatment of Cancer [EORTC] criteria) was 70% (57% partial, 13% stable); 59 (39%) of 150 patients had either a > 90% decrease in prostate-specific antigen (PSA) levels or a decline to < 4 ng/mL. Extent of disease on the bone scan was a significant predictor of response. Patients with < 6 metastatic lesions were more likely to respond. Breast pain and gynecomastia occurred in 76% and 60% of patients, respectively. Gastrointestinal toxicity was very infrequent (diarrhea, 5%) The mean drug plasma concentration was 8528 (+/- 2928) ng/mL. CONCLUSIONS: Bicalutamide, 50 mg daily, was well tolerated and has efficacy in metastatic prostate cancer. The percentage of men who had > 90% decline in PSA levels is less than observed with surgical or medical castration and has led to trials using this antiandrogen at higher doses as monotherapy.
A controlled trial of bicalutamide versus castration in patients with advanced prostate cancer.
OBJECTIVES: Bicalutamide is a new, potent antiandrogen with potential efficacy in the treatment of men with advanced prostate cancer. Although no pure antiandrogen has been well studied versus castration, potentially fewer adverse effects could occur, making such an agent a potentially useful alternative therapy. To date, three randomized controlled trials have been performed comparing these two treatments. In preliminary studies, a dose of 50 mg bicalutamide per day was selected for these trials. In two of the studies (0302, 0303), this drug was compared to either medical or surgical castration, the latter choice being made by the patient. In the third study (0301), bicalutamide was compared to bilateral orchiectomy. METHODS: Using an intention-to-treat format, the outcomes assessed were time-to-treatment failure, time-to-objective disease progression, subjective response, and survival time in men with previously untreated metastatic disease. The incidence of breast tenderness, gynecomastia, and hot flushes was also determined in both treatment arms. A quality-of-life questionnaire was administered on multiple occasions after initiation of therapy. RESULTS: Based on an analysis of > 1000 patients, the objective and subjective results favored castration over bicalutamide (50 mg/day). The hazard ratios for time-to-treatment failure (1.59), time-to-disease progression (1.62), and median survival (1.44) were all significantly greater in the castration group (P > 0.001). Another difference noted at 3 months was a significantly lower median fall in prostate-specific antigen values in the bicalutamide group (86-88% versus 96-97%). Symptomatic patients receiving bicalutamide were only 0.43 times as likely to have subjective improvement as the patients treated by castration. A comparison of pharmacologic effects showed that only the incidence of hot flushes was lower in the bicalutamide group, whereas breast tenderness and gynecomastia were more common. This difference in hot flushes, however, translated into better quality of life during the first several months with regard to sexual relations and sexual functioning. CONCLUSIONS: Bicalutamide monotherapy at 50 mg/day appears inferior to castration in overall objective and subjective response rates. Whether higher doses of bicalutamide can compete more favorably will need to be tested in further clinical trials.
Same day surgery for radical retropubic prostatectomy: is it an attainable goal?
OBJECTIVES: Economic forces are stimulating a re-evaluation of various management strategies. Recent critical pathways for radical prostatectomy have resulted in reduced length of stay to as low as 2.9 days. METHODS: The time in the operating room and recovery room, average blood loss, length of hospitalization, patient charges, and estimated hospital costs were compared for 20 patients undergoing radical prostatectomy up to 1 year before and for 27 men after initiation of a critical pathway. Under the protocol, patients receive an education booklet and preoperative teaching in preparation for early discharge and an epidural for anesthesia. An anonymous questionnaire was mailed to all patients treated by the pathway after catheter removal. RESULTS: The new pathway resulted in a significant reduction in average time in the operating room (3.7 +/- 0.4 hours versus 4.9 +/- 1.2 hours), estimated blood loss (1204 +/- 527 cc versus 1948 +/- 740 cc), and length of hospitalization (1.7 +/- 0.6 days versus 4.6 +/- 1.5 days). In addition, patient charges and hospital costs were reduced by 32% and 35%, respectively. Thirty-seven percent of the study group was discharged after 1 night compared with 0% in the group treated before the pathway was initiated. Forty-one percent of the study group was not transfused and did not donate blood. Outcome surveys completed by 25 of 27 study patients revealed an overall satisfaction of 96% with 0 of 10 patients who were discharged after one night indicating they would have preferred to be hospitalized longer. CONCLUSIONS: Conventional management of men undergoing radical prostatectomy can be safely modified while preserving patient satisfaction without increasing morbidity. Avoiding peripheral narcotics and emphasizing preoperative teaching has enabled us to reduce length of stay greatly, with same day discharge now an attainable goal.
Defining the role of surveillance in the management of localized prostate cancer.
With the dramatic increase in the detection of prostate cancer in the last 5 years, there has been an enormous challenge for physicians to recommend the "best" therapy for patients with localized prostate cancer. This challenge, however, has been difficult to meet because of the absence of well-conducted comparative trials. Because the primary goal of the urologist has been to "cure" prostate cancer and prolong life, the concept of surveillance therapy seems to be quite inappropriate; however, few other diseases have treatments that can so negatively impact on a man's daily quality of life. In addition, the natural history of this cancer, in contrast to many others, does not invariably lead to metastasis or death during the normal life span of most patients. Therefore, in contrast to physicians, many men may wish to maximize their quality of life rather than their duration of survival. This choice depends on the probability of good and bad outcomes that are possible with each treatment option. Ultimately, it is the patient's choice to make with help and unbiased guidance from the physician.
Immunohistochemical evaluation of proliferating cell nuclear antigen, prostate-specific antigen and alpha 1-antichymotrypsin in human prostate cancer.
OBJECTIVE: To determine the relationship between growth fractions defined by proliferating cell nuclear antigen (PCNA), prostate-specific antigen (PSA) and alpha 1-antichymotrypsin (ACT) staining in prostate cancer. MATERIALS AND METHODS: A total of 96 lesions, including 71 from prostate cancers and 25 from benign prostatic hyperplasia (BPH) were evaluated in microscopic sections of the prostatic tissues from 34 patients with prostate cancer. Immunohistochemical staining was performed with an avidin-biotin system using monoclonal anti-PCNA antibodies, polyclonal anti-PSA and anti-ACT antibodies. RESULTS: There was a significant difference in the mean PCNA labelling index between tissue from prostate cancer (4.2 +/- 7.1) and BPH (0.5 +/- 1.1) (P = 0.002). The mean labelling index of PCNA tended to increase with increasing Gleason score. The proportion of cells positive for PSA was significantly higher in tissue from BPH than from prostate cancer (P = 0.005). While the proportion of cells immunostaining for ACT was significantly higher in tissue from BPH compared to that from prostate cancer (P = 0.02), there was no significant difference in the proportion of ACT-positive cells among prostate cancers of differing Gleason score. The mean labelling index of PCNA decreased significantly with the increase in the proportion of PSA-positive cells (P = 0.013). There was a significant relationship between the proportion of ACT- and PSA-positive cells (P = 0.001). CONCLUSION: These results indicate a reciprocal relationship between cell growth and tumour differentiation in prostate cancer. Although the significance of ACT deserves further study, there was evidence for the complexing of PSA with ACT from the immunohistochemical studies.
Treatment of prostate cancer using external beam radiotherapy after laparoscopic pelvic lymph node dissection.
OBJECTIVES: To evaluate the results of prostatic irradiation in men with clinically localized prostate cancer and no laparoscopic evidence of nodal metastases compared with a cohort of patients who received radiation therapy with no prior surgical staging. PATIENTS AND METHODS: Thirty-one men with clinically localized prostate cancer and no evidence of pelvic nodal metastases after laparoscopic pelvic lymph node dissection received external beam radiation therapy to the prostate (65-70 Gy). The mean and median prostate specific antigen (PSA) levels in these men before treatment were 41.6 ng/mL and 28.0 ng/mL, respectively, and the mean Gleason sum was 6.1 (range 3-7). During the same interval, a group of 42 consecutive men with clinically localized prostate cancer were treated by external beam radiation therapy with no laparoscopic staging of the pelvic nodes. Treatment failure was defined by the development of bone metastases or a rising PSA level at least 6 months after the completion of radiotherapy. RESULTS: Radiation therapy was generally well tolerated after laparoscopy and no patient required hospitalization or surgery for side-effects related to the treatment. The median duration of follow-up in the 31 men who underwent laparoscopy was 21.5 months. The probability of treatment failure in this group was 41.8% and 56.3% with 24 and 30 months follow-up, respectively. When controlling for pre-treatment PSA level, grade and stage, there was no significant difference in the treatment failure rate between the groups treated with and without laparoscopic staging. CONCLUSIONS: These results suggest that there is no difference in treatment outcome with laparoscopic pelvic lymphadenectomy before external beam radiation therapy in high-risk patients who have significant pre-treatment elevations of PSA level.
Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment.
PURPOSE: We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor. MATERIALS AND METHODS: A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared. RESULTS: Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy. CONCLUSIONS: NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.
Association of nm23 protein levels in human prostates with proliferating cell nuclear antigen expression at autopsy.
OBJECTIVE: To investigate nm23-H1 gene expression in the human prostate. METHODS: The nm23-H1 protein levels of normal prostatic tissues, latent cancers of the prostate and primary and metastatic sites of clinical prostate cancers from autopsied men were evaluated using immunohistochemical analysis. Cell proliferation in serial sections using proliferating cell nuclear antigen immunoreactivity was also estimated. RESULTS: Intense nm23-H1 staining was observed in metastatic sites of clinical prostate cancers. The incidence of intense nm23-H1 staining cells in primary sites of clinical prostate cancers was significantly higher than that found in latent cancers and normal prostates (p < 0.01). The staining pattern of nm23-H1 was heterogeneous in latent cancers of the prostate. A significant relationship was observed between nm23-H1 staining and positive proliferating cell nuclear antigen staining (p < 0.01). CONCLUSIONS: These results seem to indicate that the nm23-H1 gene expression is related to cell proliferation and tumor metastatic potential, and appear to show the existence of a biologically different population of cells within the latent cancer.
Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract.
PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.
Photon neutron mixed-beam radiotherapy of locally advanced prostate cancer.
PURPOSE: In this article we present the results of mixed-beam, photon/neutron radiation therapy in 45 patients with locally advanced, bulky, or postoperative recurrent prostate cancer treated at the University of Chicago between 1978 and 1991. Survival, disease-free survival, local control, and long-term complications are analyzed in detail. METHODS AND MATERIALS: Between 1978 and 1991, 45 patients with locally advanced (> 5 cm State B2, Stage C, or Stage D1) prostate cancer underwent mixed-beam (photon/neutron) radiation therapy. Forty percent of the treatment was delivered with neutron irradiation at either the University of Chicago or Fermilab. Sixty percent of treatment was delivered with photons at the University of Chicago. Initially, the whole pelvis was irradiated to 50 photon Gy equivalent. This was followed by a boost to the prostate for an additional 20 photon Gy equivalent. RESULTS: The median follow-up for patients in this series is 72 months. The overall 5-year actuarial survival was 72%, and the 5-year disease-free survival was 45%. Thus far, 18 patients have died. Eleven patients have died from prostate cancer and 7 from other medical illness. Twenty-seven patients are alive, and 12 of these patients have recurrent and or metastatic disease. The local control rate was 89% (40 out of 45). Histologic material was available on 18 patients following treatment (i.e., prostate biopsy in 16 patients and autopsy in 2 patients) and was negative for carcinoma in 13 (72%). Significant Grade 3-5 complications occurred in 36% (16 out of 45) of the patients treated with mixed-beam radiation therapy and were related to dose and beam quality. Factors related to survival, disease-free survival, local control, and complications are analyzed. CONCLUSIONS: The survival and local control results of mixed-beam radiation therapy at the University of Chicago appear to be superior to those series using photon radiation in patients with locally advanced prostate carcinoma. Mixed-beam radiation therapy should remain an alternative to studies using dose escalation or implant techniques as a method to increase local control and survival at institutions with this capability. However, appropriate plans with high-energy neutrons are necessary to minimize complications.
Combined laparoscopic and transurethral neodymium: yttrium-aluminum-garnet laser treatment of invasive bladder cancer.
OBJECTIVES: The feasibility and efficacy of combined cystoscopic and laparoscopic neodymium: yttrium-aluminum-garnet (Nd:YAG) laser coagulation of invasive bladder cancer were investigated. METHODS: Five patients with extensive Stage T2-T3a bladder cancer who were not candidates for radical cystectomy were treated by Nd:YAG laser irradiation. All patients also underwent transperitoneal laparoscopic mobilization of the intestine away from the bladder with continuous monitoring of the laser treatment. In 2 cases, laser therapy of the serosal surface of the bladder at the site of tumor was also administered. RESULTS: The procedure was completed without complications in all 5 patients. A mean of 58,607 joules (J) of energy was delivered transurethrally with an additional 8000 to 10,000 J utilized via laparoscopy in 2 cases. Local disease recurrence was noted within 1 to 4 months in 4 of the 5 patients. Distant metastases were detected within 1 to 9 months postoperatively in 3 of 5 patients. No perioperative bowel or bladder perforation occurred. CONCLUSIONS: The use of laparoscopy allows for the safe delivery of large amounts of laser energy to the bladder. However, in this small group of patients with extensive bladder tumors, effective palliation of local disease could not be reliably achieved. Further study is necessary to determine whether treatment modifications or selection of patients with less extensive tumors will lead to better results with combined laparoscopic and cystoscopic laser therapy.