Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes.

BACKGROUND: Treatment of localized prostate cancer (PC) is controversial. This is the first randomized study comparing an open surgery procedure (radical prostatectomy) with a combination of high-dose rate brachytherapy (2×10 Gy) and external beam radiotherapy (25×2 Gy) in PC patients in Sweden 1996-2001. The two randomization arms were compared regarding differences in patients-reported outcomes, such as complications and health-related quality of life (HRQoL). MATERIAL AND METHODS: The patients had localized/locally advanced PC, clinical category T1b-T3a, N0, M0 and PSA≤50 ng/ml. All underwent total androgen blockade (six months). Self-reported HRQoL and symptoms including urinary, bowel, and sexual side effects were investigated prospectively before randomization and 12 and 24 months after randomization. A total of 89 patients were randomized and completed the EORTC QLQ C-33 and EORTC PR-25 questionnaires. RESULTS: Over the study period, there were no discernible differences in HRQoL, or complications between the two groups. Emotional functioning, however, improved statistically significantly over time, whereas Social functioning decreased, and financial difficulties increased. No statistically significant differences in group-by-time interactions were found. The survival rate was 76%. Only eight patients (9%) died of PC. CONCLUSION: Open radical prostatectomy and the combined high-dose rate brachytherapy with external beam radiation appeared to be comparable in the measured outcomes. It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study.

Effect on prostate volume following neoadjuvant treatment with an androgen receptor inhibitor monotherapy versus castration plus an androgen receptor inhibitor in prostate cancer patients intended for curative radiation therapy: A randomised study.

To avoid pubic arch interference, prostate cancer patients are treated with neoadjuvant androgen deprivation therapy (ADT) to achieve prostate volume (PV) reduction prior to radiation treatment. The aim of the present randomised study was to compare the effects on PV of two regimens of ADT, an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. Consecutive patients with non-metastatic prostate cancer were included in a randomised neoadjuvant study, comparing an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. PV was assessed prior to the start of endocrine neoadjuvant treatment and prior to the start of radiation therapy (RT). PV assessment was performed by transrectal ultrasound. A total of 110 patients were included. Final sample constituted 88 (80%) patients due to lack of PV information. Castration plus an androgen receptor inhibitor was more effective in PV reduction compared with an androgen receptor inhibitor alone (P<0.001). Planning target volume decreased in the combination arm. There was no significant difference in clinical or demographic or length of neoadjuvant hormonal treatment between the groups. Overall, a significantly larger PV reduction was achieved by castration plus androgen receptor inhibitor, as compared with androgen receptor inhibitor monotherapy. The PV reduction, however, appeared not to translate into better health associated quality of life during the subsequently given curative intended combined EBRT and HDR-brachytherapy. Potential differences between these two treatments regarding anti-tumor effects on micro metastatic disease and radiation potentiating effect remains to be addressed in future prospective trials.

Higher sexual interest with androgen receptor inhibitor monotherapy than with castration plus an androgen receptor inhibitor in prostate cancer patients treated with curative radiotherapy, but otherwise small health-related quality of life differences: A randomised prospective 18-month follow-up study.

PURPOSE: To prospectively study differences in health-related quality of life (HRQoL) in patients with localised/locally advanced prostate cancer (PC) treated with curative intended radiation therapy and randomised to androgen receptor inhibitor monotherapy treatment versus castration plus an androgen receptor inhibitor used continuously. Time to Prostate Specific Antigen (PSA) relapse, time to symptomatic metastasis and overall survival (OS) were also described for the two groups. PATIENTS AND METHODS: From 2005 to 2011, a total of 110 patients were randomised at a ratio of 1:1. HRQoL was assessed at six time points: before randomisation, before radiotherapy (RT) start and 9, 12, 15 and 18 months after randomisation, using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and EORTC QLQ-PR25. RESULTS: At the 3-month follow-up, statistically significant differences between the two groups were found for overall quality of life (p = 0.006), fatigue (p = 0.023), sexual interest (p < 0.001) and urinary problems (p = 0.036). Small clinical differences were noted for overall quality of life, role functioning, fatigue, pain, sleeping problems and urinary problems. At that assessment point, clinical differences between the groups were substantial regarding sexual interest and moderate regarding sexual functioning (the latter indicated only by patients reporting having sexual interest at baseline). All statistical and clinical differences favoured the androgen receptor inhibitor monotherapy arm. At 18 months after randomisation, statistically significant differences were found for cognitive functioning (p = 0.040) and sexual interest (p = 0.011), both favouring the androgen receptor inhibitor monotherapy arm. CONCLUSION: The results suggest that neo-adjuvant androgen receptor inhibitor monotherapy might be preferred compared to castration plus an androgen receptor inhibitor before curative intended RT in men with localised/locally advanced PC, with higher levels of HRQoL, especially concerning sexual interest. HRQoL differences over time were small. The observation time and study sample were too small for evaluating time to PSA progression and OS. Further studies are needed to confirm the results. The study was registered in, identification number NCT02382094.

Less satisfaction with information in patients with prostate cancer treated with surgery and salvage radiotherapy compared with patients treated with curative radiotherapy alone, despite similar health-related quality of life.

BACKGROUND: This study examined patient perception of information received, satisfaction with that information, and its relation to health-related quality of life (HRQoL) and clinical and demographic variables before, during, and after radiotherapy (RT) for localized prostate cancer. PATIENTS AND METHODS: In 2010, 2 questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and EORTC QLQ information module [QLQ-INFO25]) were sent to 660 consecutive patients with prostate cancer who had undergone or were to undergo RT with curative intent between December 2006 and March 2010. RESULTS: The response rate was 92%. Although most patients (69%) were satisfied with the information they received, statistically significant differences were found for all but 2 EORTC QLQ-INFO25 variables, favoring those who were treated with RT alone compared with those treated with both prostatectomy and salvage RT. Statistically significant associations between all HRQoL variables and satisfaction with information were found; higher levels of satisfaction were associated with better functioning and lower levels of symptoms and problems. CONCLUSION: Satisfaction with the information received was studied in patients with prostate cancer with localized disease. Despite the fact that the majority of patients reported being satisfied with the information received, there is room for improvement, especially regarding "the disease," "other services," "different places of care," and "things you can do to help yourself." Patients treated with both prostatectomy and salvage RT reported significantly lower levels of satisfaction with information received and of having received significantly less information than did patients treated with RT alone.

Prostate cancer cell lines lack amplification: overexpression of HER2.

The potential overexpression of HER2 in prostate cancer cells has attended significant interest during the past few years, both as potential target for HER2 pathway focused therapy and as a mechanism involved in the progression to androgen independence. Conflicting results have been reported concerning HER2 status on clinical material, differences which generally have been attributed to methodological differences. Nevertheless, HER2 has been utilized for targeted therapy of prostate cancer in a number of preclinical studies and is still regarded as an exciting target molecule. In this study, the HER2 status of three widely used prostate cancer cell lines and corresponding xenografts has been analysed. By use of validated and FDA approved analytical staining techniques none of these cell lines or xenografts were shown to overexpress/amplify HER2, as demonstrated by immunohistochemistry and fluorescence in situ hybridization. These findings are important for the interpretation and understanding of the therapeutic effects when developing drugs targeting HER2 in prostate cancer cell lines and also emphasize the importance of using broad and validated analytical techniques.