Deferred Treatment Research Articles

Need for Hospital Care and Palliative Treatment for Prostate Cancer Treated with Noncurative Intent

Purpose We investigate the ultimate need for palliative treatments and hospital care in prostate cancer patients treated with noncurative intent. Materials and Methods A retrospective analysis was done of 514 prostate cancer patients who died between 1988 and 1990. Results Of the patients who later died of prostate cancer 61 percent needed 1 or more palliative treatments (transurethral resection of the prostate, radiation treatment or upper urinary tract diversion) before death. An average of 5 weeks was spent in the hospital due to prostate cancer. Conclusions Patients who failed deferred treatment (thus dying of prostate cancer) needed a considerable amount of hospital care and palliative therapy before they ultimately died of the disease.

Expectant Management of Early Stage Prostatic Cancer: Swedish Experience

To learn about the natural history of untreated early stage prostatic cancer (stage T0-2NXM0) progression-free, disease specific, overall survival and the need for palliative care were evaluated in a population-based and regionally well defined cohort from Sweden. Complete followup, with a mean observation of 12.5 years, was achieved in 223 consecutively diagnosed, eligible patients (98%) of all ages. Patients with progression were hormonally treated (orchiectomy or estrogens) if they had symptoms. After a mean of 12.5 years only 23 patients (10%) had died of prostate cancer and 125 of 148 deaths (84%) were of other causes. The 10-year disease specific survival rate was 85% (95% confidence interval 79 to 91%) and was equally high (89%) in a subgroup of 58 patients who met current indications for radical prostatectomy. The progression-free 10-year survival rate was 55% (95% confidence interval 46 to 63%) but in 49 of 77 patients local growth provided the only evidence of progression and endocrine treatment was generally successful in these cases. Following an initial increase, the rate of disease progression and death from prostate cancer decreased during the last years of followup.The low disease specific mortality rate, especially in patients with highly and moderately differentiated tumors, means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison. One such trial is in progress in Sweden and Finland evaluating deferred treatment and radical prostatectomy. As of the beginning of December 1993, 330 patients were included in the study.

Conservative approaches to the management of localized prostatic cancer.

The management of early stage prostatic cancer is controversial. Pertinent literature concerning the conservative management of early stage prostatic cancer by early endocrine therapy (EET) or by deferred treatment (DT) was reviewed. EET has not been systematically studied. Available evidence suggests that early stage prostatic cancer often progresses slowly and that DT results in a cancer-specific mortality of approximately 80% at 10 years. EET warrants clinical investigation. DT is a management option, at least in patients with a life expectancy of 10 years or less.

Reducing doxorubicin cardiotoxicity in the rat using deferred treatment with ADR-529.

The purpose of this study was to evaluate the optimal timing of ADR-529 administration to protect rats treated with doxorubicin (DXR) against drug-induced cardiotoxicity. Complete electrocardiographic monitoring (QRS complex, S alpha T segment and T wave) and the histopathological analysis of cardiac tissue were used to assess the degree of heart damage produced in female rats treated with ten i.v. doses of 1 mg/kg DXR over a period of 15 weeks; body-weight increase and survival were also analyzed to evaluate the toxicity of treatments. Cardiac alterations induced by DXR were compared with those occurring in animals receiving 20 mg/kg i.v. ADR-529 at 30 min prior to DXR administration, starting at the first, third, or sixth DXR dose and given until the end of the study (15th week). Rats treated with DXR were severely cardiomyopathic, showing progressive and irreversible ECG alterations (QRS-complex and S alpha T-segment widening and T-wave flattening) and marked degeneration of the myocardium (myocyte vacuolation, myofibrillar loss, and endomyocardial fibrosis). The most effective cardiac protection was provided by the administration of ADR-529 beginning with the first or third DXR dose. Delaying treatment with ADR-529 until the sixth DXR dose resulted in a significant reduction in its therapeutic action on heart damage. A significant difference in body-weight increase and survival was observed between the treatment groups: ADR-529 injected prior to the first DXR dose significantly protected animals from DXR toxicity, but this schedule was significantly more toxic than the administration of ADR-529 beginning with the third or sixth DXR dose. Taking into account the degree of cardiac protection and the toxicity of combination treatments, the results of the present study demonstrate the superiority of ADR-529 given prior to the third DXR dose over the other schedules tested. This finding suggests that significant protection against DXR-induced chronic cardiotoxicity in the rat can be obtained using deferred treatment with ADR-529.

Deferred Treatment in Localized Prostatic Cancer

The natural history of early prostatic cancer has been evaluated in 223 patients with localized (T0-2, NX, M0), newly diagnosed, untreated prostatic cancer in a population-based study. No initial treatment was given and after an observation time of 66-150 months, 73 patients (33%) have progressed (25 with metastases) and 109 died but only 17 of prostatic cancer. Cumulative progression-free survival after 5 and 10 years was 73.1% and 64.3% respectively. Observed survival after 5 and 10 years was 67.3% and 44.1% respectively and the corresponding corrected survival 93.8% and 88.7%. Fifty-eight of the 223 patients filled the present criteria for radical prostatectomy. With only hormonal manipulation after symptomatic progression the corrected survival was very high, 98.0% after 5 years and 89.1% after 10 years among these 58 patients. As a result of this study a randomized trial comparing deferred treatment with radical prostatectomy in this group of patients has been started in Finland and Sweden.

Immediate versus deferred treatment for early prostatic cancer.

The diagnosis of early (non-metastatic) prostatic cancer is dependent upon the patient presenting himself with symptoms or for routine rectal examination or ultrasound screening. Diagnosis in the absence of symptoms is more common outside the United Kingdom and as a result the opportunity to treat such patients occurs more commonly in other countries. The treatment options for the different stages are reviewed and the evidence for their effectiveness is considered. A review of the literature yields conflicting evidence of the efficacy of and the necessity to institute early therapy. This basic gap in our current knowledge should be filled when the results of the existing Medical Research Council (MRC) clinical trial of immediate and deferred orchidectomy are available.

Incidental versus manifest prostatic carcinoma

The problem in managing incidental prostatic carcinoma is whether deferred treatment or active therapy should be preferred. Eighty-six consecutive patients with prostatic carcinoma diagnosed at TUR-P during 1979-83 were studied retrospectively. Seventeen of the patients (20%) had incidental prostatic carcinoma. Incidental carcinomas were significantly more well differentiated histologically than manifest carcinomas. The striking difference between incidental and manifest prostatic carcinomas appeared when the clinical course was considered. Only one patient with incidental carcinoma developed symptoms requiring endocrine therapy, against 31 patients with manifest carcinoma (p less than 0.01). It is therefore concluded that the distinction between manifest and incidental prostatic carcinoma is justified and that deferred treatment is sufficient in most patients presenting with incidental prostatic carcinoma at TUR-P.

Cisplatin combination chemotherapy in advanced seminoma

Thirty-one patients were treated with cisplatin combination chemotherapy for advanced seminoma (26 Stage III or bulky Stage II testicular, and five disseminated extragonadal). Seventeen (89%) of 19 patients not previously pretreated and four (80%) of five who had received only abdominal irradiation entered continuous complete remission (CR), versus only two (28%) of seven patients who had received extensive infra- and supradiaphragmatic radiotherapy. Results were not significantly influenced by stage, human chorionic gonadotropin (HCG) titers and histologic subgroups, whereas patients with lactic dehydrogenase (LDH) values exceeding 500 mIU/ml did worse (50% continuous CR rate in 12 cases) than those with normal or less elevated titers (89% continuous CR rate in 19 cases). After a median follow-up period of 34 months (range, 12+ to 77+ months), 23 patients (74.5%) remain alive in continuous CR, two (6%) died in CR and another one (3%) entered CR after deferred treatment of residual disease. Five patients (16%) died of cancer. Toxicity was severe in extensively irradiated patients, but it was acceptable in those not pretreated and in those who had received only subdiaphragmatic radiotherapy. Cisplatin combination chemotherapy can be successfully and safely used as the primary treatment of choice in patients with advanced seminoma. It is also an excellent salvage therapy for patients who had received subdiaphragmatic irradiation only. On the contrary, it is very difficult to treat with chemotherapy extensively irradiated patients.