Search

Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient’s comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients’ quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients’ quality of life., SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundThe appropriate time to discontinue chemotherapy at the end of life has been widely discussed. In contrast, few studies have investigated the patterns of endocrine treatment near death. In this study, we aimed to investigate the end-of-life endocrine treatment patterns of older women with metastatic breast cancer and explore characteristics associated with treatment.MethodsA retrospective cohort study of all older women (age >= 65 years) with hormone receptor-positive breast cancer who died in Sweden, 2016 - 2020. We used routinely collected administrative and health data with national coverage. Treatment initiation was defined as dispensing during the last three months of life with a nine-month washout period, while continuation and discontinuation were assessed by previous use during the same period. We used log-binomial models to explore factors associated with the continuation and initiation of endocrine treatments.ResultsWe included 3098 deceased older women with hormone receptor-positive breast cancer (median age 78). Overall, endocrine treatment was continued by 39% and initiated by 5% and of women during their last three months of life, while 31% discontinued and 24% did not use endocrine treatment during their last year of life. Endocrine treatment continuation was more likely among older and less educated women, and among women who had multi-dose drug dispensing, chemotherapy, and CDK4/6 use. Only treatment-related factors were associated with treatment initiation.ConclusionMore than a third of women with metastatic breast cancer continue endocrine treatments potentially past the point of benefit, whereas late initiation is less frequent. Further research is warranted to determine whether our results reflect overtreatment at the end of life once patients' preferences and survival prognosis are considered.

Breast cancer (BC) is the most common cancer among women in Sweden and worldwide. Adjuvant endocrine therapies are effective, yet 20-30% patients experience disease relapse. Altered cholesterol metabolism is an emerging hallmark of breast cancer proliferation and endocrine therapy resistance. Studies have shown that the use of cholesterol-lowering medications (statins) reduces the risk of disease recurrence in a subset of patients. However, the patterns of breast cancer recurrence remains poorly understood, and treatment predictive biomarkers are needed. 27-hydroxycholesterol (27HC), an oxysterol synthesized from cholesterol by the enzyme CYP27A1, is a selective estrogen receptor (ER) modulator. It has been shown that 27HC is an important mediator that links cholesterol and breast cancer pathology. Aims: The main aims of this thesis were i) to explore the molecular features associated with the heterogeneous response of BC cells to statin treatment alone or in combination with endocrine therapy, ii) investigate the patterns of BC recurrence in patients with post-diagnosis statin use, and iii) characterize CYP27A1 expression in primary BC in relation to tumor pathological features and prognosis. Methods: In papers I and V, BC cell lines were treated with statins and/or endocrine treatments to study its impact on cell growth, lipid metabolism, endocrine signaling, and other metabolic pathways using a combination of global transcriptional profiling and molecular assays. In paper II, the prognostic impact of statin use on disease recurrence was investigated in the Malmö Diet and Cancer Study Cohort. Disease recurrence rates were compared between post-diagnosis statin users versus non users using Cox regression models to compute crude and adjusted hazard ratios. In paper III and IV, the prognostic impact of CYP27A1 expression, as measured by immunohistochemistry and/or RNAscope, was evaluated in three independent cohorts of BC patients. In paper IV, the impact of

This thesis investigated whether the development of metastases in patients treated for hormone-sensitive breast cancer can be predicted on the basis of the DNA methylation profile of the tumor. The thesis consists of a main study investigating the prognostic value of DNA methylation in Dutch patients, and a number of technical studies that made the analyses in the main study possible. The conclusion of the study is that DNA methylation has a predictive value for the occurrence of metastases in women treated for hormone-sensitive breast cancer, but that this predictive value is no better than already existing clinical factors.

Purpose: There are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade. Methods: A population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively. Results: After propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34–0.77, p value < 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41–1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14–5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10–3.38, p = 0.345). Conclusion: Our study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.

Bakground: The aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant. Methods: A consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified. The primary outcome of the study was time to disease progression (TTP) during the treatment with Fulvestrant in overweight and obese women compared to patient with normal BMI. Results: In total, 173 patients were enrolled in the study cohort, amongst these, 141 patients received both Fulvestrant and Als and 32 received only Fulvestrant. No statistical significant association was observed between the three BMI categories and TTP, during Fulvestrant treatment (p = 0.136). The rates of objective response and clinical benefit due to Fulvestrant were similar among patients with normal weight, overweight and obesity, respectively. Conclusions: No difference in treatment efficacy was seen between normal, overweight and obese women with metastatic HR+BC, when treated with Fulvestrant. Until further research with prospective studies is available, there is no evidence to support any modification in how Fulvestrant treatment is used in patients with metastatic breast cancer in regard to BMI.

Background Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). Patients and methods A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. Results Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. Conclusions In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score, SCOPUS: re.j, info:eu-repo/semantics/published

Hormone receptor positive breast cancer (HR-positive BC) is the most frequent BC subtype (∼70%), with endocrine treatment constituting its therapeutic cornerstone; despite its efficacy, endocrine resistance can develop, clinically as a relapse or a progression of the early or advanced disease respectively, hence necessitating alternative treatments. Over the last two decades, improved understanding of the molecular mechanisms of endocrine resistance has been achieved, with numerous targeted agents undergoing clinical development. Despite the multifactorial genesis of endocrine resistance, fuelled not only by alternative oncogenic signaling pathways of tumor cells, but also by tumor microenvironment-mediated mechanisms, successful clinical development of new agents has been recently noted. However, predictive biomarkers for accurate ‘navigation’ across the different treatment options are urgently needed. In this article, we present a thorough overview of the different clinical scenarios of BC endocrine resistance, and the recent advances in endocrine treatment, we describe the basic molecular mediators of endocrine resistance and the respective targeted agents undergoing clinical development; finally, we provide our perspective on the future of BC endocrine treatment., SCOPUS: re.j, info:eu-repo/semantics/published

Young patients with breast cancer (BC) are often concerned about treatment-induced infertility and express maternity desire. Conception after BC does not seem to affect outcome, but information in estrogen-receptor positive (ER+) disease is not definitive. From September 2012-March 2013, 212 evaluable patients with ER+ early BC, <37years at diagnosis, from 5 regions (Europe/US/Canada/Middle-East/Australia) answered a survey about fertility concerns, maternity desire and interest in a study of endocrine therapy (ET) interruption to allow pregnancy. Overall, 37% of respondents were interested in the study; younger patients (≤30 years) reported higher interest (57%). Motivation in younger patients treated >30 months was higher (83%) than in older women (14%), interest was independent of age in patients treated for ≤30 months. A prospective study in this patient population seems relevant and feasible. The International-Breast-Cancer-Study-Group (IBCSG), within the Breast-International-Group (BIG) - North-American-Breast-Cancer-Groups (NABCG) collaboration, is launching a study (POSITIVE) addressing ET interruption to allow pregnancy., SCOPUS: ar.j, info:eu-repo/semantics/published

The appropriate selection of medical therapeutic interventions in breast cancer patients is a daily challenge for medical oncologists and takes into account disease characteristics such as stage at diagnosis, age and menopausal status, aggressiveness of the disease, and presence or absence of key therapeutic targets such as hormonal receptors and HER2. Knowledge of treatment-related toxicities as well as patient’s comorbidities, preferences, age, and so on is a critical component of an optimal estimation of the benefit versus harm ratio of a specific therapy.This chapter reviews the side effects of the four main medical treatment modalities for breast cancer: chemotherapy, ­endocrine therapy, biologic agents, and bone-modifying therapeutics in terms of frequency, monitoring, and practical management., SCOPUS: ch.b, info:eu-repo/semantics/published

Detecting signals in the mammalian target of rapamycin (mTOR), and the estrogen receptor (ER) pathways for prediction of treatment response may be a future clinical tool in primary breast cancer. Here, we investigated the validity and value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen sensitivity in vitro and in two independent tamoxifen randomized postmenopausal breast cancer cohorts. In addition, the prognostic value of the S6Ks was evaluated. A simultaneous knockdown of the S6Ks in ER-positive breast cancer cells resulted in G1 arrest, and tamoxifen-induced G1 arrest was in part S6K1+S6K2 dependent, suggesting separate roles in proliferation and in tamoxifen response. We found S6K1 to correlate with HER2 and cytoplasmic Akt activity, whereas S6K2 and phosphorylated S6K were closer connected with ER positivity, low proliferation and nucleic p-Akt. Treatment prediction and prognosis were evaluated by immunohistochemical staining. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen treatment effect, compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation. Patients with a combination of S6K1 nuclear accumulation and S6K2 cytoplasmic accumulation in the tumor cells had no tamoxifen benefit. Also, S6K1 and S6K2 activation, indicated by p-S6K-t389 expression, was associated with low benefit from tamoxifen compared with untreated patients. In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis. This was not evident for variations in S6K2 or p-S6K-t389 expression. In conclusion, the mTOR targeted kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity andintracellular localization may provide biomarkers for breast cancer treatment, allowing for identification of a group of patients less likely tobenefit from tamoxifen and thus in need of an alternative or additional treatment.

Background: Prostate cancer patients have an increased risk of fractures as a consequence of skeletal metastases and osteoporosis induced by endocrine treatment. Data on incidence of fractures and risks in subgroups of men with prostate cancer are sparse. Our aim with this study is to report the risk of fractures among men with prostate cancer in a nationwide population-based study. Patients and methods: We identified 76,600 Swedish men diagnosed with prostate cancer 1997-2006 in the Prostate Cancer Data Base (PCBaSe) Sweden and compared the occurrence of fractures requiring hospitalisation with the Swedish male population. Results: Only men treated with gonadotropin releasing-hormone (GnRH) agonists or orchiectomy had increased incidence and increased relative risk of fractures requiring hospitalisation. Men treated with GnRH agonists had 9.8 and 6.3/1000 person-years higher incidence of any fracture and hip fracture requiring hospitalisation than the general population. The corresponding increases in incidence for men treated with orchiectomy were 16 and 12/1000 person-years, respectively. Men treated with orchiectomy, GnRH agonists, and antiandrogen monotherapy, had SIR for hip fracture of 2.0 (95% Confidence Interval 1.8-2.2), 1.6 (95% CI 1.5-1.8) and 0.9 (95% CI 0.7-1.1), respectively. Men treated with a curative intent (radical prostatectomy or radiotherapy) or managed with surveillance had no increased risk of fractures. Older men had the highest incidence of fractures while younger men had the highest relative risk. Conclusion: Prostate cancer patients treated with GnRH agonists or orchiectomy have significantly increased risk of fractures requiring hospitalisation while patients treated with antiandrogen monotherapy had no increase in such fractures. In absolute terms the excess risk in men treated with GnRH agonists corresponded to almost 10 extra fractures leading to hospitalisation per 1000 patient-years. Effects on bone density should be considered for

BACKGROUND: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events. OBJECTIVE: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis. DESIGN, SETTING, AND PARTICIPANTS: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden. MEASUREMENTS: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events. RESULTS AND LIMITATIONS: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28-1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated. CONCLUSIONS: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis.

BACKGROUND: The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa. METHODS: The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa. RESULTS: In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7% (95% CI, 5.6%-8.5%), 1.3% (0%-2.6%), and 1.6% (0.6%-2.6%) for these 3 cancers, respectively. From a uro-oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort. CONCLUSIONS: Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms.

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.

One of the great challenges in breast cancer treatment today is to customize adjuvant treatment to each patient’s individual needs. To do this it is necessary to learn more about the prognostic and treatment predictive factors that determine the risk of relapse and response to a certain mode of treatment. This thesis describes studies on the effect of amplified in breast cancer 1 (AIB1), a coactivator of the oestrogen receptor, on prognosis and tamoxifen response through a controlled trial on premenopausal patients randomized to tamoxifen or a control group. AIB1 was found to be a negative prognostic factor, although patients with high AIB1 responded very well to tamoxifen. The findings were validated in two independent cohorts, one consisting of premenopausal patients not receiving tamoxifen, and the other of pre- and postmenopausal patients receiving tamoxifen. It has recently been suggested that the effect of AIB1 is modified by paired box 2 gene product (PAX2). PAX2 is a transcription factor important during embryogenesis, and may also play a role in carcinogenesis. This is the first time PAX2 has been investigated in well-defined cohorts of patients receiving or not receiving tamoxifen. PAX2 was not found to affect prognosis on its own, or to modify the effect of AIB1. The second part of this thesis focuses on contralateral breast cancer (CBC). Within their lifetime, previous breast cancer patients have a 2-20% risk of developing a second tumour in the contralateral breast. From the trial on premenopausal patients randomized to tamoxifen or control, it was found that without tamoxifen 12% developed CBC within a median follow-up period of 14 years. This risk was even higher in the youngest women (<40 years), in which 20% developed CBC. Treatment with tamoxifen reduced the risk by 50% in all patients, and by 90% in the youngest women. Since CBC is still a rather rare event, previous studies are often small or based only on register data. Detailed patient, tumour

Current treatment of metastatic breast cancer (MBC) aims at achieving meaningful clinical responses, improved quality of life, long-term remissions, prolonged survival, and dares to hope for a cure in a small percentage of cases. This article will discuss both consensus and controversies in the management of MBC in the context of the new evolving breast cancer molecular classification. Hormonal therapy remains the mainstay of management of MBC Luminal A and B. Data is emerging on management of ErbB2-positive HR-positive MBC by combining hormonal manipulation and targeted anti-ErbB2 therapy and has recently received regulatory approval in Europe and USA. The optimal use and duration of single agent or combination chemotherapy is discussed. Data and controversies surrounding the use of newer agents such as nab-paclitaxel, ixabepilone, eribulin, and PARP inhibitors as well as trastuzumab is reviewed. Better understanding of pathophysiology has paved the way for the introduction of newer anti-ErbB2 agents such as lapatinib, pertuzumab, T-DM1 and neratinib. Controversies regarding bevacizumab and anti-angiogenesis are discussed. Bisphosphonates have significantly reduced skeletal related events and made significant improvements in the quality of life of patients with MBC. Newer anti-RANK Ligand antibodies show promising results. Significant advances in the understanding of molecular biology of breast cancer have been made and should lead to an improvement in the outcome of MBC. More possibilities of cure can become an attainable goal in the near future., Journal Article, Review, SCOPUS: re.j, info:eu-repo/semantics/published

Objective. Radical prostatectomy (RP) has become the most common treatment for localized prostate cancer in Sweden. Outcome is extremely good for pT2 stage with Gleason score 6 or less, but more than every fourth operated patient will have a pT3 stage on full amount specimen histology. According to several reports the risk of biochemical recurrence is quite high, especially in stage pT3, on active surveillance after surgery alone. In 1994 the authors recognized this fact at their clinic and decided to apply a new multimodality treatment concept. Material and methods. During 10 years, between 1 January 1995 and 1 January 2005, 98 pT3 patients were treated with a triple treatment: 8 months of neoadjuvant/adjuvant luteinizing hormone-releasing hormone (LH-RH) analogue treatment, RP and immediate adjuvant radiotherapy (RT) 3 months after RP. RT was delivered to 60 Gy in 30 fractions to the prostatic bed to all the patients. The cumulative risk of progression was calculated with the Kaplan-Meier method. The impact of risk factors was evaluated by the Cox proportional hazard model. Results. Ninety-eight (74 pT3a and 24 pT3b) patients were followed with a mean observation time from operation until October 2007 of 71.6 (median 65.5, range 35-146) months. The mean follow-up time to biochemical failure, death or last measurement of prostate-specific antigen (PSA) was 57.8 (median 57.0, range 3-132) months. Fifteen patients out of 98 had experienced biochemical failure. Only Gleason score had an independent impact on the risk of PSA progression. Complications were mild and temporary and no serious adverse events were registered. Conclusions. Patients with locally advanced prostate cancer have a high risk of progression after RP as single therapy. Postoperative RT has been shown to improve the outcome. Neoadjuvant/adjuvant hormonal therapy has been shown to improve the outcome after RT. Bringing this knowledge together offering a multimodality therapy with neoadjuvant/adjuvant