Quantification of changes in bone scans of patients with osseous metastases of prostatic carcinoma.
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Bone Neoplasms↗
Biomedical subjects
G R Prout
Publications and source records attributed to G R Prout.
The usefulness of serum acid phosphatase in monitoring patients with advanced prostate carcinoma.
The usefulness of serum acid phosphatase (SAP) in monitoring patients with advanced prostate carcinoma has been questioned. We reviewed a series of 59 patients with stage D2 prostate carcinoma. All patients had extended follow-up through at least one clinical relapse, or death. Responses to a variety of therapies were characterized as absent, subjective, or objective. All patients with an elevated pre-treatment SAP that fell to normal following therapy had prolonged survivals and improved prognoses. Conversely, all patients with an elevated SAP which did not normalize following therapy had poorer survivals. Among 36 objective responses to therapy, the SAP was elevated prior to or simultaneous with disease progression in 33 (93% sensitivity). In each ease where the pretreatment SAP normalized following therapy, any subsequent elevation in SAP above normal was always associated with clinical evidence of disease progression (100% specificity). Changes in SAP following therapy correlate well with both disease regression and disease progression in patients with advanced prostatic carcinoma.
Alkaline Phosphatase↗
Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Cancer Group.
A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.
Adult↗
Radio-chemotherapy for invasive carcinoma of the bladder.
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Antineoplastic Combined Chemotherapy Protocols↗
13-cis-retinoic acid in chemoprevention of superficial bladder cancer. The National Bladder Cancer Group.
Animal studies indicate that 13-cis-retinoic acid (CRA) inhibits bladder tumor growth and is effective in treating patients with serious dermatologic disorders. A trial of CRA in patients at high risk for recurrent Ta, T1 tumors was initiated at an experimental dose of 0.5 mg/kg/d in three divided doses, increasing to 1 mg/kg/d at four weeks. Treatment of twenty eligible patients lasted for six months with an additional 24 month follow-up period. One patient was later excluded due to toxicity resulting in an early dose reduction. Eight patients stopped treatment before three months; of these five, had recurrences within three months, one developed pulmonary metastasis, and one developed a T2G3 tumor. Four patients stopped treatment between three and six months; three of them had recurrences before one year and one had no evidence of disease at seven years. Seven patients completed the course; of these three had recurrences within six months, and three more had recurrences at 8, 15, and 45 months, respectively. Toxicity was nearly universal; cheilosis, conjunctivitis, pruritus, joint and eye pain, flashing lights, and erythrocyte sedimentation rate (ESR) over 60 were all noted. The lack of positive results and the frequency and severity of toxicity led to termination of the study.
Carcinoma, Transitional Cell↗
Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.
Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.
Adult↗
Interval report of a phase I-II study utilizing multiple modalities in the treatment of invasive bladder cancer. A bladder-sparing trial.
Clinicians at the Massachusetts General Hospital have used two cycles of methotrexate, cisplatin, and vinblastine (MCV) before radiotherapy and cisplatin in 53 patients with muscle-invasive bladder cancer. Eleven patients did not complete the protocol, but overall, the toxicity was not formidable. Of the total patients accessioned, 34 are alive. Of the 34 patients in the series who completed the full treatment protocol, the estimated survival rate at 54 months is 77%. This interim analysis suggests that the treatment is achieving at least limited success in saving lives and bladders.
Adult↗
Multi-drug resistance of a doxorubicin-resistant bladder cancer cell line.
A bladder tumor cell line resistant to doxorubicin (MGH-U1R) has been established previously by culturing a human transitional cell carcinoma cell line (MGH-U1) in increasing concentrations of the drug. MGH-U1R is 40 times more resistant to doxorubicin than MGH-U1. In the present study, MGH-U1R was evaluated for its multi-drug resistance or pleiotropism by testing against other chemotherapeutic agents. MGH-U1R was found to be 188 times more resistant to vinblastine and 13 times more resistant to etoposide than MGH-U1, while remained sensitive to bleomycin. Taken together with earlier evidence that the resistance of MGH-U1R to doxorubicin can be reversed by a calcium-channel blocker verapamil, and the measured over-expression of the mdr1 gene in these cells, MGH-U1R has the characteristic multiple drug resistance properties similar to other established doxorubicin resistant carcinoma cell lines. MGH-U1R may be a useful model for the development of strategies in overcoming drug-resistance in the treatment of transitional cell carcinoma.
Bleomycin↗
Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.
Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.
Aged↗
Historical and modern role of cystoscopy and bladder mucosal biopsy in detecting bladder cancer in a high-risk population.
The use of cystoscopy and bladder biopsy to screen cohorts of persons with no history of bladder carcinoma would be unsatisfactory because of the low prevalence of the disease, even in the highest risk occupations. Cystoscopy/biopsy should follow noninvasive modern-day techniques that can be used for screening at reasonable cost and no risk to the workers involved. Dipstick testing for hematuria, urinary cytology, flow cytometry, quantitative fluorescence image analysis, and other emerging technologies are far more useful as screening methods. Examples of bladder tumors and benign lesions are included to demonstrate the heterogeneity of bladder carcinoma and the difficulties the urologist faces in deciding which lesions may be malignant. Positive preliminary tests increase the sensitivity and specificity of the diagnostic examination.
Biopsy↗
Detection of exfoliated bladder cancer cells by monoclonal antibodies to tumor-associated cell surface antigens.
Monoclonal antibodies (Mabs) to human tumor antigens have potential for tumor detection and treatment. For bladder carcinoma, the detection of exfoliated tumor cells in urinary specimens may be accomplished with Mabs reacting to tumor cell-surface components. This method may be useful for screening and monitoring carcinogen-exposed workers. A Mab generated by our laboratory, 3G2-C6, reacts with high affinity to a cell-surface component expressed by bladder tumor cells. The potential utility of this Mab in detecting exfoliated tumor cells was evaluated in bladder wash specimens. The Mab method detected positive cells in 87% (56/64) of specimens from patients with bladder cancer, including a great majority with grade 1 tumor and carcinoma in situ, superior to the routine cytology done on the same specimens. Cells in specimens from patients with urinary calculi, chronic cystitis, and history of bladder cancer also reacted with the Mab, suggesting that other stimuli can induce antigen expression. The Mab method can also be performed on urine samples, thus allowing evaluation of the ability of the Mab to identify premalignant, malignant, and other abnormal exfoliated cells in urine. The Mab method represents a unique opportunity to develop noninvasive detection of bladder cancer and to monitor and screen bladder cancer high-risk groups.
Antibodies, Monoclonal↗
A progress report on the results of multimodality therapy for muscle-invasive bladder cancer.
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Aged↗
Proton radiation as boost therapy for localized prostatic carcinoma.
A 160-MeV proton beam has been modified to irradiate patients with localized tumors by using convention treatment schedules. This proton beam has the physical advantage of megavoltage x-rays of reducing the radiation dose to normal tissues adjacent to the tumor volume. A perineal proton technique used as boost therapy (2,000 to 2,500 rads) was evaluated in the definitive irradiation of 17 patients with localized prostatic carcinoma. This technique allows repeated daily treatment of the carefully defined target volume with a precision of +/- 2 mm. Total dose to the prostatic tumor, but not to the posterior rectum, has been increased by 500 to 700 rads. After 12 to 27 months of observation, no noteworthy rectal reaction has developed in a patient, easily managed urethral strictures have developed in two patients, and all but one are locally controlled.
Adenocarcinoma↗
Bladder carcinoma as a systemic disease.
Pne hundred and fifty-one patients with transitional cell carcinoma of the bladder who were evaluated by conventional means preoperatively underwent a radical cystectomy. They were then classified according to the highest known pathological stage, first site of postoperative metastasis and the temporal relationship of the cystectomy to the appearance of the metastasis. Fifty patients developed metastases, 80% of which were proven histologically. Thirty-nine of fifty patients (78%) who developed metastases did so within a year of cystectomy. Extent of local tumor was directly related to the incidence of positive pelvic nodes. Metastases occurred most commonly in lung and bone. Soft tissues of the pelvis were involved in thirteen (16%) of the patients who developed metastatic carcinoma and those patients with positive pelvic nodes were more likely to have these kinds of recurrent disease. These evaluations suggest that the metastases must be present at cystectomy or as a result of it. The data imply the existence of appreciable heterogeneity among patients and/or their invasive bladder carcinoma. Disseminated but silent metastases suggest that a relationship between the primary tumor and the occurrence of metastatic disease may exist. Knowledge of this relationship is very important in planning subsequent therapeutic strategies.
Carcinoma, Transitional Cell↗
A longitudinal study of patients with superficial bladder carcinoma successfully treated with weekly intravesical thio-tepa.
Herein is reported further results of a prospective clinical investigation to determine the effect of weekly intravesical bladder instillation of thio-tepa in the treatment of superficial bladder cancer. Patients with superficial bladder carcinoma were treated according to 2 protocols. The first protocol consisted of patients with persistent tumor who were treated with weekly thio-tepa for 8 weeks. Of the 33 patients 18 responded to this therapy, and they and 24 other patients who had been rendered free of tumor by transurethral resection alone were assigned to the second protocol in which patients either were treated with monthly instillations of thio-tepa or they were observed every 3 months in a prescribed fashion. Monthly thio-tepa instillations had no significant effect in lowering the recurrence rate in either group. However, in the patients who had responded to weekly thio-tepa benefit was noted in terms of 1) fewer recurrences, with 8 of 18 (44 per cent) previously pre-treated patients having a recurrence versus 19 of 24 patients (79 per cent) previously untreated, 2) delay in tumor recurrence with an interval free of tumor of 15.1 months in pre-treated patients versus 4.3 months in the untreated group and 3) diminished frequency of new tumors (0.33 recurrences yearly) in comparison to the untreated group (1.78 recurrences yearly). The remaining patients are free of tumors at 15.7 months average followup.
Carcinoma, Transitional Cell↗
Comparison of procarbazine, imidazole-carboxamide and cyclophosphamide in relapsing patients with advanced carcinoma of the prostate.
In this third cooperative chemotherapy trial of the National Prostatic Cancer Project 165 patients with histologically confirmed, relapsing clinical stage D prostatic cancer were randomized to receive either imidazole-carboxamide, procarbazine or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on initial therapy were crossed over or randomized to receive an alternate drug. There were 129 patients available for comparison of treatments. The objective response rates (partial regression plus stable disease) were 26% for cyclophosphamide, 27% for imidazole-carboxamide and 14% for procarbazine. Subjective responses were noted in pain relief, improvement in performance status and weight gain. Procarbazine was associated with excessive toxicity, resulting in many patients (28%) discontinuing therapy within the first 3 weeks and closure of this particular arm of the study. The regimen of initial imidazole-carboxamide therapy with a later cross-over to cyclophosphamide when the disease continues to progress is associated with the longest increase in survival. Imidazole-carboxamide and cyclophosphamide appear to be active agents in advanced prostatic cancer and are worthy of continued use in this disease.
Aged↗
The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.
Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9% of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.
Chlorambucil↗
Intravesical thio-tepa: a study of 3H-thymidine uptake in normal urothelium and FANFT-induced tumors in rats.
Treatment of superficial low-grade bladder cancer often incorporates intravesical instillations of the alkylating agent thio-TEPA. Current dosages and administration schedules are empiric inasmuch as cytokinetic data are sparse. The FANFT-induced bladder rat tumor model closely approximates human bladder cancer. This study measuring 3H-thymidine uptake identified peaks of maximal synthetic activity at 3 and 9 days after thio-TEPA exposure in both normal and neoplastic urothelium. Thus, repeat instillation at these intervals may improve cytotoxicity and overall response rate.
Animals↗