Hormone-resistant prostate cancer with symptomatic pelvic tumours: patient survival and prognostic factors.

OBJECTIVES: To determine the survival and investigate the prognostic significance of immunohistochemical variables and clinical factors in patients with hormone-resistant prostate cancer (HRPC) and symptomatic pelvic tumours, in whom preliminary observations indicated that survival exceeded the median 8-10 months of patients with HRPC and painful bone metastases. PATIENTS AND METHODS: Seventy-five patients with HRPC referred for palliative pelvic radiotherapy between 1980 and 1996 were identified. For all patients at least two prostate biopsies had been obtained, one before primary hormone treatment and at least one after clinical progression despite androgen deprivation (HRPC biopsy). Bone scans at the time of referral were assessed. The medical records were reviewed for clinical variables of possible prognostic significance. Histological grade was recorded, and prostate-specific antigen (PSA), androgen receptors (ARs), Ki-67 and p53 determined immunohistochemically. In 18 HRPC specimens the degree of AR amplification was analysed. RESULTS: Positive staining for ARs was high in the HRPC biopsies, although there was no association with AR amplification. Ki-67 positivity increased after the development of HRPC. The median (range) survival was 14 (1-141) months; age < 65 years was associated with increased survival. In a multivariate analysis the following variables remained independent prognostic factors for survival from the time of the HRPC biopsy: bone metastases (0-10 vs > 10 lesions, P < 0.001), low Ki-67 score (0 vs 1-3, P = 0.006) and low p53 positivity score (0 vs 1-3, P = 0.014) in the HRPC biopsy. CONCLUSIONS: The median survival of patients with HRPC and pelvic tumours requiring palliation seems to exceed that of patients with HRPC and dominating painful bone metastases by at least 4-6 months. Simple clinical (bone metastases) and immunohistochemical variables (Ki-67, p53) enable patients with particularly long survival times to be identified, and in whom palliative treatment needs to be improved.

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study.

Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m(-2), every third week up to a cumulative dose of 500 mg m(-2). Biochemical response [> or = 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of > or = 3 weeks' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a > or = 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (> or = 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of > or = 50% PSA decrease in patients with HRPC.

Changing incidence and delay of testicular cancer in southern Norway (1981-1992).

METHODS: The medical records of 352 patients with newly diagnosed testicular cancer were reviewed. Patients were orchiectomized during three 2-year periods (1981/82, 1986/87, 1991/92) and were referred for further treatment to the Norwegian Radium Hospital. They represented 96% of all cases with unilateral testicular cancer occurring within a defined area in the southern part of Norway. RESULTS: An increase in testicular cancer patients was registered, mainly between the second and third time periods (61% increase). Gynaecomastia was recorded in 7% of all patients (seminoma: 6%; non-seminoma: 8%). Serum tumour markers (alpha-fetoprotein and/or human choriogonadotropin) were elevated before orchiectomy in 51% of the evaluated patients. During the studied 12-year period, considering seminoma and non-seminoma patients combined, the overall median delay decreased from 18 to 14 weeks (p = 0.006), the overall median diagnostic delay decreased from 14 to 10 weeks (p = 0.04) and the median treatment delay decreased from 37 to 28 days (p = 0.002). Due to increased frequency of stage I patients, introduction of an outpatient-based surveillance policy and improved administrative routines of the Health Care System, the median time of hospitalization was reduced from 37 (1981/82) to 9 days (1991/92). In seminoma, but not in non-seminoma patients, an overall delay of less than 16 weeks from the onset of symptoms was correlated with the incidence of stage I disease. The cancer-related 5-year survival rate for all 352 patients was 99%, without significant difference between the three periods under investigation. A patient's delay of more than 3 months was correlated with a significantly decreased 5-year survival rate if all patients are considered (p = 0.02). CONCLUSION: (1) The significant increase of the incidence of testicular cancer in the southern part of Norway remains unexplained and warrants intensified search for aetiological factors of this malignancy. (2) The Health Care Service is challenged to make available sufficient resources for the rapid diagnosis, treatment and follow-up of the increasing number of new patients with testicular cancer, following modern principles of toxicity-reduced and resource-saving treatment. (3) Attempts should be made to shorten the patient's and doctor's delay by awareness campaigns and postgraduate education of general practitioners. The importance of the determination of serum tumour markers in patients with testicular masses should, in particular, be emphasized together with the significance of gynaecomastia in the young adult male.