Fatigue in hormone-naïve prostate cancer patients treated with radical prostatectomy or definitive radiotherapy.

Chronic fatigue (CF) is a distressing symptom that follows cancer treatment; however, it has rarely been studied in hormone-naïve prostate cancer survivors after radical prostatectomy (RP) or definitive radiotherapy (RAD). We investigated CF in prostate cancer survivors after RP or RAD as monotherapy and explored associations between CF and medical and psychosocial variables. A population-based, cross-sectional postal survey in 2006 included Norwegian hormone-naïve survivors with the diagnosis of prostate cancer in 2004 who were treated with RP (n=337) or RAD (n=184). The primary outcome variable was prevalence of CF (defined as fatigue lasting 6 months or longer). Twelve to 32 months after RP and RAD, 13.4 and 26.1% of the patients after, respectively, RP and RAD reported CF inversely associated with pretreatment age (P=0.003). In multivariate analysis, high neuroticism, post-treatment co-morbidity, pain, urinary and intestinal dysfunction, but not sexual dysfunction, were positively associated with reporting CF. Further studies of CF in prostate cancer survivors should take into consideration the survivors' pretreatment medical and psychosocial situation.

Association between serum 25(OH)D and death from prostate cancer.

Based on observations that for certain cancers, mortality varies according to sun exposure, vitamin D has been proposed to influence on disease progression. This study aims to investigate whether serum levels of 25(OH)D are associated with prognosis in patients with prostate cancer. In total, 160 patients with a serum sample in the JANUS serum bank were included. For 123 patients a pre-treatment serum sample was taken, whereas 37 of the patients had received hormone therapy prior to the blood collection. The serum level of 25(OH)D was classified as low (<50 nmol l(-1)), medium (50-80 nmol l(-1)) or high (>80 nmol l(-1)). A Cox proportional hazard regression model was used to assess the association between serum 25(OH)D and cancer mortality. During follow-up, 61 deaths occurred, of whom 52 died of prostate cancer. The median time of follow-up was 44.0 months (range, 1.2-154.6). Serum 25(OH)D at medium or high levels were significantly related to better prognosis (RR 0.33; 95% CI 0.14-0.77, RR 0.16; 95% CI 0.05-0.43) compared with the low level. Analysis restricted to patients receiving hormone therapy gave a stronger association. The serum level of 25(OH)D may be involved in disease progression and is a potential marker of prognosis in patients with prostate cancer.

High prostate cancer mortality in Norway: influence of Cancer Registry information?

Norway has among the highest prostate cancer mortality rates in the world. The aim of the present project was to assess whether this can be explained by the unique routine procedure of information transfer from the Cancer Registry of Norway (CR) to the Norwegian Cause of Death Registry (COD Registry). Norwegian prostate cancer patients deceased during 1996 were identified (n=2012). The information basis of the official mortality statistics was reviewed by two physicians, who independently identified the underlying cause of death, primarily prostate cancer or not, supplemented by consensus of two other physicians. The coding was done in two steps; first without, then with CR information. Project physicians identified 1063 deaths from prostate cancer as compared to the official number of 1161, with discrepancy as to prostate cancer death in 126 deceased. Information from the CR increased the project's age-adjusted (world standard population) prostate cancer mortality rate by less than 1% (from 22.7 to 22.9 per 100,000). In conclusion, the high rates of prostate cancer mortality in Norway could not be explained by information transfer from the CR to the COD Registry.

Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence.

Novel palliative strategies for patients with androgen-independent prostate cancer (AIPC) include targeting the epidermal growth factor receptor (EGFR) family. The aim of the present study was to investigate intrapatient changes of EGFRs during the development of AIPC. In total, 106 symptomatic AIPC patients were identified in whom prostatic biopsies (adenocarcinoma) were available both before the start of androgen deprivation (PRTR biopsy) and after the development of AIPC (AIPC biopsy). All four known subgroups of the EGFR family were determined by immunohistochemistry (IHC): c-erbB-1 (EGFR), c-erbB-2 (HER2/neu), c-erbB-3 (HER3) and c-erbB-4 (HER4). Moderate to strong membrane-specific staining was recorded semiquantitatively (<10% vs >/=10%=IHC stained tumour cells: 'negative' vs 'positive' staining). The medical records were reviewed for clinical variables. During the development of AIPC, intrapatient changes occurred in two opposite directions for each of the four EGFRs: negativity changed to positivity, and vice versa, statistically significant only for the increase of c-erbB-1 expression (P=0.001). The c-erbB-2 expression in the AIPC biopsy was associated with a significantly shorter survival from the time of the AIPC biopsy (P=0.029). Our results support ongoing therapeutic attempts of EGFR inhibition in subgroups of patients with prostate cancer. Further research is needed to understand the function of EGFRs in this malignancy.

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.

[Prostate-specific antigen in the follow-up of conservatively treated prostatic cancer]. / Prostataspesifikt antigen ved oppfølging av konservativt behandlet prostatakreft.

The determination of serum prostate specific antigen (PSA) has made the diagnosis of prostate cancer easier. PSA is also used extensively in the follow-up of patients, both treated and untreated. On the basis of material from 308 patients who were mainly managed conservatively, we discuss the usefulness of this practice. It is important to monitor PSA after radical treatment because an increase may indicate local recurrence. In some patients this may lead to further treatment with cure as the aim. For patients under observation only, or those being treated by endocrine intervention, the value of regular PSA measurements is less certain. Where such patients were followed up for at least three years, we found considerable overlaping of PSA values among patients with different outlooks. Within the present therapeutic possibilities it may be better to base their management on clinical signs rather than on PSA. Regular measurements of PSA lead to focusing on this variable, causing unnecessary distress to patients months, or even years, before clinical progression of the disease.

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.