Biomedical subjects
Publications and source records attributed to Z Wajsman.
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OBJECTIVES: To assess the risk of continued intravesical therapy and delayed cystectomy in the management of superficial bladder cancer refractory to bacillus Calmette-Guérin (BCG) therapy. METHODS: We retrospectively reviewed the medical records of 24 patients who underwent an experimental intravesical treatment with BCG plus interferon alpha-2b or valrubicin for transitional cell carcinoma of the bladder. All patients had Stage Tis and/or T1 transitional cell carcinoma and had failed multiple prior courses of intravesical therapy, including at least one course of BCG. RESULTS: Patients were followed up for a median of 28.5 months (range 6 to 48). One patient died of unrelated disease. All other patients were alive at last follow-up. Fourteen patients with preserved bladder were continuing cystoscopic surveillance: four had no recurrence, five had recurrence limited to the mucosa (Ta or Tis) and became free of disease after an additional course of intravesical therapy, and five had recurrent Ta or Tis or positive cytologic findings. The remaining 9 patients underwent radical cystectomy. All pathologic specimens showed no evidence of progression to muscle-invasive disease. Tis of the resected ureters in 6 and involvement of the prostate in 4 of the 9 patients (three in the urethral ducts and glands and one in the prostatic stroma) were noted. CONCLUSIONS: A select group of patients with BCG-refractory transitional cell carcinoma and a poor surgical risk for cystectomy may benefit from continued intravesical therapy without a significant risk of progression. However, a cautious approach to this treatment modality is recommended, and very close follow-up is necessary to detect bladder recurrences and involvement of the upper tract and prostatic urethra.
BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.
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PURPOSE: We discuss the subject of a second opinion for interpretations of anatomical pathology from the perspective of patient care. MATERIALS AND METHODS: We grouped 150 cases involving pathological review at our institution into 3 categories depending on the effect on patient care. RESULTS: Of 29 interpretive discrepancies 14 resulted in treatment changes but 7 of these 14 may have been interpreted differently by other practice groups. CONCLUSIONS: Whether the second opinion represents an interpretive error or a legitimate difference of opinion, the result may affect patient care. Patients referred for treatment among practice groups should have pathological findings reviewed as part of a complete assessment by the new physicians.
OBJECTIVES: To assess in a pilot study the safety, tolerability, and technical feasibility of administering intravesical valrubicin immediately after transurethral resection of bladder tumors (TURBT) in patients with superficial bladder cancer and to evaluate the optimal dose of valrubicin and its systemic absorption. METHODS: Twenty-two patients with recurrent or newly diagnosed Stage Ta or T1 transitional cell tumors received a single dose of 400 mg, 600 mg, or 800 mg of intravesical valrubicin immediately after TURBT. Four patients thought to be at high risk of recurrence were followed up with five additional doses of 800 mg valrubicin, given weekly. RESULTS: The use of valrubicin after TURBT was generally well tolerated. Little evidence was found to suggest a direct relationship among the dose of valrubicin, the time between the end of TURBT and drug instillation, and the occurrence of most bladder symptoms. The most commonly reported adverse events included dysuria (77%), hematuria (59%), and urgency/frequency (23%). Pharmacokinetic analyses revealed that the mean systemic exposure to valrubicin and its metabolites depended on the extent of the TURBT and the damage to the bladder wall. CONCLUSIONS: The results of this study indicated that administration of valrubicin immediately after TURBT is feasible.
PURPOSE: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. MATERIALS AND METHODS: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least 1 course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. RESULTS: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. CONCLUSIONS: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.
PURPOSE: Urinary diversion is an alternative treatment for conditions such as radiation and interstitial cystitis, neurogenic bladder and severe incontinence. The subsequent complication rate may reach 60% due to the retained nonfunctional bladder. The subsequent cystectomy rate may be as high as 20% because of pyocystis, hematuria, pelvic pain and rarely bladder cancer. We describe simple cystectomy involving bladder removal without the adjacent structures, avoiding deep pelvic dissection. MATERIALS AND METHODS: Ileal conduit or continent diversion and simple cystectomy were performed for crippling bladder symptoms secondary to neurogenic bladder, pelvic radiation, hematuria and/or severe incontinence in 12 women and 7 men with a mean age of 63 years. We performed urinary diversion and simple cystectomy only when all conservative means of treatment had failed. The majority of patients had multiple co-morbidities, previous surgeries and pelvic radiation. An average of 5 conservative procedures (range 2 to 10) had been done before simple cystectomy. None of these patients had urothelial malignancy. Simple cystectomy was done concomitantly with urinary diversion in 13 cases and later as a separate procedure in 6 due to complications of a retained nonfunctional bladder. RESULTS: Mean followup was 15 months. No mortality was associated with surgery. For simple cystectomy only mean operative time was 30 minutes and mean estimated blood loss was 300 cc. Median time from symptom presentation to cystectomy was 35 months and mean hospital stay was 7 days. In all cases symptoms were dramatically alleviated. No morbidity was directly attributable to simple cystectomy. CONCLUSIONS: Simple cystectomy is well tolerated and should be performed at urinary diversion to avoid later complications of the retained bladder. Technically this procedure is not demanding and is relatively easy to perform even after previous pelvic radiation.
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From what is known about the testicular and adrenal origins of testosterone, and the testosterone dependency of prostate cancer, treatment with combined androgen blockade (CAB) by castration plus an antiandrogen was expected to be beneficial to patients. A number of early studies verified this hypothesis, but the findings needed to be confirmed in large, randomized, prospective studies. Modest but significant benefits of CAB were seen when treatment with leuprorelin plus flutamide was compared with leuprorelin alone. Of note was the increased benefit from CAB seen in patients with minimal metastatic prostate cancer, a finding that needed to be confirmed. A study comparing orchidectomy plus nilutamide with orchidectomy alone showed significant benefits of CAB in terms of time to progression and overall survival. However, a recent major NCI study revealed no benefits for CAB with respect to survival, even for patients with minimal metastatic disease. Results from other clinical studies have been conflicting, perhaps because of the method of castration or differences in antiandrogen used. Before the question of whether CAB significantly benefits patients can be fully answered, a clearer understanding of the interactions between antiandrogens, luteinizing hormone-releasing hormone agonists and receptors, and of the response of prostate cancer to these, is needed.
PURPOSE: We studied the effect of the combination of androgen deprivation with salvage surgery in patients with radiorecurrent prostate cancer. MATERIALS AND METHODS: Salvage cystoprostatectomy or radical prostatectomy was performed in 29 patients with radiorecurrent prostate cancer. Of the 29 patients 24 had been treated with neoadjuvant hormonal therapy before salvage surgery, while in 5 an initial trial of androgen deprivation had failed preoperatively. RESULTS: The positive surgical margin rate for all patients was 31%. Margin involvement correlated strongly with disease specific and disease-free survival. At a mean followup of 5.3 years disease specific survival was 95% in men with negative surgical margins compared with 44% in those with positive surgical margins (p = 0.002). Similarly, clinical and biochemical disease-free survival was 80% in patients with negative surgical margins, while only 44% of those with positive surgical margins remained disease-free (p = 0.05). Surgical margins were positive in 80% of the men in the androgen deprivation failure group and in 21% in the neoadjuvant hormonal therapy group (p = 0.001). The disease specific survival rate after an initial trial of androgen deprivation failed was only 20% compared with 92% after neoadjuvant hormonal therapy was given preoperatively (p = 0.001) CONCLUSIONS: The combination of neoadjuvant hormonal therapy with salvage surgery for radiorecurrent prostate cancer resulted in a low incidence of surgical margin involvement, which correlated strongly with disease specific and disease-free survival. Patients with radiorecurrent prostate cancer in whom an initial trial of androgen deprivation fails appear to be poor candidates for salvage prostatectomy.
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PURPOSE: Tests to detect recurrent bladder neoplasms are limited and none is consistently accurate. Recent studies suggest that the bladder tumor antigen (BTA) test, an agglutination reaction for basement membrane complexes, is superior to voided urine cytology in clinical practice. We compared BTA and voided urine cytology to bladder washings and cystoscopy, emphasizing diagnostic yield among patients with causes of basement membrane complexes other than bladder cancer. MATERIALS AND METHODS: Random voided urine specimens from 67 patients with a history of bladder neoplasms were collected before cystoscopy and bladder washing. Urine also was obtained from 34 patients with inflammatory bladder conditions including 5 with a history of prostate cancer. Each urine was tested for BTA according to a commercial kit. Positive results were indicated by yellow on a test pad. Blinded to all other results, each urine and each bladder washing were examined microscopically, and a positive test had malignant/suspicious cells. Bladder biopsies were performed when endoscopic lesions were seen. Specimens were grouped into 4 categories: group 1--biopsy proved bladder neoplasm, group 2--history of bladder cancer but not biopsy proved, group 3--history of prostate cancer and group 4--no history of urological cancer. RESULTS: Voided urine cytology was positive in 54% of specimens from patients with biopsy proved bladder neoplasms compared to 29% for BTA. Relative yield for voided urine cytology versus BTA was not changed if all group 2 cases having a positive bladder washing and positive cystoscopy were assumed to have bladder cancer, nor was relative yield altered by subsequent short-term followup. Of voided urine specimens 14% from group 1 patients and 41% from group 2 patients had scant cells. Overall diagnostic yield was superior for bladder washing. False-positive BTA occurred in 7 of 34 patients with no history of urological or prostate cancer. There were no false-positive voided urine cytology interpretations in these groups. CONCLUSIONS: BTA is not superior to voided urine cytology in detecting bladder neoplasms and may be limited by false-positive reactions in patients with other causes of basement membrane complexes in urine. Voided urine samples may be limited by high frequency of hypocellularity. Of 34 patients with a hypocellular urine specimen 4 had biopsy proved bladder cancer. Bladder washing yields best results but requires instrumentation. No test, including cystoscopy, is accurate always.
PURPOSE: We determined whether decreases in prostate specific antigen (PSA) would occur after withdrawal of double-blinded antiandrogen therapy with flutamide or bicalutamide for clinical progression or increasing PSA concentration in patients receiving combined androgen blockade for advanced prostate cancer. MATERIALS AND METHODS: PSA concentrations were determined weekly for at least 6 weeks and then every other week for 6 weeks in 22 patients with stage D2 prostate cancer. All patients were withdrawn from antiandrogen therapy (8 flutamide and 14 bicalutamide) due to progression or an increasing PSA concentration. Objective response was evaluated before antiandrogen withdrawal and at week 12. RESULTS: In 4 of 8 patients (50%) withdrawn from flutamide and 4 of 14 (29%) withdrawn from bicalutamide serum PSA concentrations decreased by 50% or more. PSA responses after withdrawal of flutamide therapy occurred within the first few days, whereas those after withdrawal of bicalutamide therapy occurred within 4 to 8 weeks. Of 4 patients assessed for objective response 2 had stable disease and 2 had progression. A PSA response was observed in the 2 patients with stable disease but not the 2 with progression. CONCLUSIONS: For patients with stage D2 prostate cancer and disease progression or an increasing PSA concentration, withdrawal of antiandrogen therapy with bicalutamide or flutamide may result in a PSA response. The time to PSA response is longer with bicalutamide than with flutamide. The clinical significance of the antiandrogen withdrawal phenomenon is unknown.
PURPOSE: We strove to characterize the clinicopathologic features of a rare malignant tumor involving the urogenital system. MATERIALS AND METHODS: Of 109 reported cases of desmoplastic small round-cell tumor, 25 have involved organs ordinarily evaluated and treated by urologists. Experience based on these cases plus 2 from our files forms the basis of this review. RESULTS: The term desmoplastic small round-cell tumor has been applied to a rare, highly malignant neoplasm that occurs most often in the abdominal cavity and is described in the nonurological literature. This cancer has distinctive histological, immunohistochemical and ultrastructural features. Several reports suggest a characteristic genetic abnormality. All reported patients who have tumors involving the genitourinary structures have been treated with chemotherapy, but prognosis has been poor. CONCLUSIONS: The literature on desmoplastic small round-cell tumor indicates that a significant percentage of these rare malignancies involve genitourinary organs. In most cases, tumors have been unresectable surgically and treatment has been multidrug chemotherapy. Response to treatment has been poor, with only 3 of 25 determinate cases free of disease when reported.
Both radical cystectomy and diverticulectomy for the treatment of neoplasms arising in a vesical diverticulum have resulted in poor survival, mainly secondary to early metastatic spread. In this study, nine patients were treated with a multispecialty approach in hopes of eradicating both local and distant disease. All patients underwent a combination of therapeutic modalities with three patients undergoing pre-operative radiotherapy (RT) and diverticulectomy; diverticulectomy and chemotherapy (three patients); diverticulectomy with chemotherapy and pre-operative RT (two patients); and definitive RT with cisplatin (one patient). With a mean follow-up of 4.0 years (median 3.2), four patients are free of disease, two are dead of other causes, one patient has developed an invasive recurrence, one patient is alive with metastatic disease, and one patient is dead of disease. Five patients (55%) developed local recurrences. Disease-specific survival for the group was 89%. Surgical monotherapy has been ineffective in controlling both local and metastatic disease in patients with diverticular tumors. This study suggests a significant benefit from systemic chemotherapy and RT when combined with surgery for these neoplasms.
Mitomycin is used extensively for the prevention of recurrence of superficial bladder cancer. Most treatment regimens of mitomycin are long term, since this seems more effective in preventing recurrence. During treatment some patients develop cystitis of variable severity, which may lead to mucosal ulcerations and cessation of treatment. We report a case in which long-term treatment with mitomycin, following a single episode of transitional cell bladder cancer, has led to bladder fibrosis and loss of its function, without evidence of tumor recurrence.