Natural History Of Prostate Cancer Research Articles

Pathophysiology of Bone Loss in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy and Lifestyle Modifications for the Management of Bone Health: A Comprehensive Review.

Androgen-deprivation therapy (ADT) is a systemic therapy administered for the management of advanced prostate cancer (PCa). Although ADT may improve survival, long-term use reduces bone mass density (BMD), posing an increased risk of fracture. Considering the long natural history of PCa, it is essential to preserve bone health and quality-of-life in patients on long-term ADT. As an alternative to pharmacological interventions targeted at preserving BMD, current evidence recommends lifestyle modifications, including individualized exercise and nutritional interventions. Exercise interventions include resistance training, aerobic exercise, and weight-bearing impact exercise, and have shown efficacy in preserving BMD. At the same time, it is important to take into account that PCa is a progressive and debilitating disease in which a substantial proportion of patients on long-term ADT are older individuals who harbor axial bone metastases. Smoking cessation and limited alcohol consumption are commonly recommended lifestyle measures in patients receiving ADT. Contemporary guidelines regarding lifestyle modifications vary by country, organization, and expert opinion. This comprehensive review will provide an evidence-based, updated summary of lifestyle interventions that could be implemented to preserve bone health and maintain quality-of-life throughout the disease course of PCa.

Role of metabolic imaging in diagnosis of primary, metastatic, and recurrent prostate cancer.

The present review describes the current role of metabolic imaging techniques such as multiparametric MRI (mpMRI), magnetic resonance spectroscopic imaging (MRSI), hyperpolarized MRSI, and positron emission tomography (PET) in the diagnosis of primary prostate cancer, surveillance of low-grade disease, detection of metastases, and evaluation of biochemical recurrence after therapy. The natural history of prostate cancer ranges from indolent disease that is optimally monitored by active surveillance, to highly aggressive disease that can be lethal. Current diagnostic methods remain imperfect in noninvasively distinguishing between silent versus aggressive tumors. Hence, there is a high demand for noninvasive imaging techniques that offer insight into biological behavior of prostate cancer cells. Characterization of prostate cancer metabolism is a promising area to provide such insights. Metabolic imaging may allow for greater detection and ultimately characterization of tumor based on aggressiveness and spread. Hence, it has the potential to monitor tumor activity, predict prognostic outcomes, and guide individualized therapies.

PD16-06 SURROGATE ENDPOINTS FOR OVERALL SURVIVAL FOR PATIENTS WITH METASTATIC HORMONE-SENSITIVE PROSTATE CANCER IN THE CHAARTED TRIAL

INTRODUCTION AND OBJECTIVE:Given the long natural history of prostate cancer (PC), intermediate clinical endpoints (ICEs) might aid in study design and expedite drug approvals, if surrogacy is met....

Comparison of 18F-sodium fluoride PET/CT, 18F-fluorocholine PET/CT and diffusion-weighted MRI for the detection of bone metastases in recurrent prostate cancer: a cost-effectiveness analysis in France

BackgroundThe diagnostic performance of 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18F-fluorocholine PET/CT (FCH) and diffusion-weighted whole-body magnetic resonance imaging (DW-MRI) in detecting bone metastases in prostate cancer (PCa) patients with first biochemical recurrence (BCR) has already been published, but their cost-effectiveness in this indication have never been compared.MethodsWe performed trial-based and model-based economic evaluations. In the trial, PCa patients with first BCR after previous definitive treatment were prospectively included. Imaging readings were performed both on-site by local specialists and centrally by experts. The economic evaluation extrapolated the diagnostic performances of the imaging techniques using a combination of a decision tree and Markov model based on the natural history of PCa. The health states were non-metastatic and metastatic BCR, non-metastatic and metastatic castration-resistant prostate cancer and death. The state-transition probabilities and utilities associated with each health state were derived from the literature. Real costs were extracted from the National Cost Study of hospital costs and the social health insurance cost schedule.ResultsThere was no significant difference in diagnostic performance among the 3 imaging modalities in detecting bone metastases. FCH was the most cost-effective imaging modality above a threshold incremental cost-effectiveness ratio of 3000€/QALY when imaging was interpreted by local specialists and 9000€/QALY when imaging was interpreted by experts.ConclusionsFCH had a better incremental effect on QALY, independent of imaging reading and should be preferred for detecting bone metastases in patients with biochemical recurrence of prostate cancer.Trial registrationNCT01501630. Registered 29 December 2011.

Single-Dose Focal Salvage High Dose Rate Brachytherapy for Locally Recurrent Prostate Cancer

AimsTo evaluate focal high dose rate (HDR) brachytherapy in locally recurrent prostate cancer. Materials and methodsPatients with biochemical relapse after non-surgical primary treatment for localised prostate cancer were selected after a negative screen for metastatic disease. Template mapping biopsies combined with multiparametric magnetic resonance imaging were used to identify the location of the tumour and the focal clinical target volume. The planning aim dose prescription was 19 Gy. Outcome measures were biochemical relapse-free survival and toxicity using International Prostate Symptom Score and Common Terminology Criteria for Adverse Events (version 4.0) scores. ResultsBetween March 2013 and December 2018, 50 patients underwent salvage HDR brachytherapy. The median follow-up was 21 months (range 1–53). Biochemical progression-free survival at 2 and 3 years was 63% and 46%, respectively. On multivariate analysis, only prostate-specific antigen nadir ≤0.5 ng/ml post-salvage (P = 0.03, hazard ratio 0.04) was associated with biochemical progression-free survival. Relapse was associated with distant metastases in 11/13 patients in whom this was investigated. Late grade 3 genitourinary toxicities were gross haematuria (three patients), severe lower urinary tract symptoms (two patients), erectile dysfunction (one patient) and urethral stricture requiring surgery (four patients). No acute and late grade 4 or 5 genitourinary and no grade 3 or higher gastrointestinal toxicities were recorded. ConclusionsFocal salvage HDR monotherapy achieves biochemical control in 46% of patients at 3 years with acceptable toxicity rates in selected patients. Biochemical relapse was related to a post-salvage prostate-specific antigen nadir of ≥0.5 ng/ml. Long-term outcomes are needed to assess the impact on the natural history of prostate cancer in these patients.

Single Dose Focal Salvage High-Dose-Rate Brachytherapy for Locally Recurrent Prostate Cancer

To evaluate focal high dose rate (HDR) brachytherapy in locally recurrent prostate cancer. Patients with biochemical relapse after non-surgical primary treatment for localized prostate cancer were selected after a negative screen for metastatic disease. Template mapping biopsies combined with multiparametric MRI were used to identify the location of the tumor and the focal clinical target volume. The planning aim dose prescription was 19Gy. Outcome measures were biochemical progression free survival (bPFS) and post treatment gastrointestinal (GI) & genitourinary (GU) toxicities using CTCAE v4.0 scores. Between March 2013 and December 2018, fifty-seven patients were included in this study. Median follow-up was 21 months bPFS at 2 and 3 years were 61% and 48%, respectively; median time to biochemical failure (BF) was 17 months. On multivariate analysis, the bPFS was best predicted by PSA nadir ≤0.5 ng/ml post-salvage (p<0.0001, hazard ratio 33.82), PSA doubling time ≥ 12 months post-salvage (p=0.01, hazard ratio 0.05) and primary PSA (p=0.01, hazard ratio 2.98). Late grade 3 GU toxicities were gross hematuria (5%), severe lower urinary tract symptoms (4%), erectile dysfunction (2%), and urethral stricture requiring surgery (5%). No acute and late ≥grade 4 GU and ≥grade 3 GI toxicities were recorded. Focal salvage HDR monotherapy is an effective treatment with acceptable toxicity rates in selected patients. Strong predictors of biochemical control in this study were PSA nadir post- salvage ≤ 0.5 ng/ml, PSA doubling time post salvage≥ 12 months and presenting PSA. Long term outcomes are needed to assess the impact on the natural history of prostate cancer in these patients.

Evolution of definitive external beam radiation therapy in the treatment of prostate cancer.

Although the clinical significance of a diagnosis of prostate cancer for some men is debated, for many men it leads to significant morbidity and mortality. Radical treatment of clinically localized prostate cancer has been shown to improve survival in men with intermediate or high-risk disease. There is no high level evidence to support the superiority of radical prostatectomy, with or without adjuvant or salvage external beam radiotherapy in comparison to definitive radiotherapy with or without androgen deprivation, and the choice should be individualized. External beam radiation therapy practices are in constant evolution, and numerous strategies have been investigated to improve either efficacy or reduce toxicity, or both. Randomized controlled trials investigating strategies to improve efficacy, reduce toxicity, or both of external beam radiotherapy have been reviewed in men with prostate cancer without nodal or distant metastases. These strategies include the use of neo-adjuvant and adjuvant androgen deprivation, dose-escalation, hypofractionation, whole pelvic radiation therapy, incorporation of improved imaging, image- guided radiation therapy, and adjuvant systemic therapy. The evidence to date for these strategies is discussed, noting limitations in applying the results of reported trials to men treated in contemporary settings. A number of strategies have shown improvements in biochemical control using external beam radiotherapy. To date, only with the use of androgen deprivation therapy has this translated into improvements in disease specific and overall survival. This may reflect the long natural history of prostate cancer and high incidence of competing risks. Technological advances have enabled dose escalation with reduced toxicity, of paramount importance given the long natural history. The use of external beam radiation therapy in prostate cancer is evolving with numerous strategies incorporated to improve outcomes. The optimum dose and fractionation and use of androgen deprivation or systemic adjuvants for each man is unclear based on current evidence and prognostic and predictive parameters. Patient preferences play an important role in chosen therapy. It is hoped that future studies better capture all prostate cancer- and treatment- related morbidity to clarify the optimal therapy choices for each man with prostate cancer.

464 - Natural history of prostate cancer on active surveillance: Stratification by MRI using the PRECISE recommendations in a UK cohort over 11 years

464 - Natural history of prostate cancer on active surveillance: Stratification by MRI using the PRECISE recommendations in a UK cohort over 11 years

A natural history model for planning prostate cancer testing: Calibration and validation using Swedish registry data.

Recent prostate cancer screening trials have given conflicting results and it is unclear how to reduce prostate cancer mortality while minimising overdiagnosis and overtreatment. Prostate cancer testing is a partially observable process, and planning for testing requires either extrapolation from randomised controlled trials or, more flexibly, modelling of the cancer natural history. An existing US prostate cancer natural history model (Gulati et al, Biostatistics 2010;11:707-719) did not model for differences in survival between Gleason 6 and 7 cancers and predicted too few Gleason 7 cancers for contemporary Sweden. We re-implemented and re-calibrated the US model to Sweden. We extended the model to more finely describe the disease states, their time to biopsy-detectable cancer and prostate cancer survival. We first calibrated the model to the incidence rate ratio observed in the European Randomised Study of Screening for Prostate Cancer (ERSPC) together with age-specific cancer staging observed in the Stockholm PSA (prostate-specific antigen) and Biopsy Register; we then calibrated age-specific survival by disease states under contemporary testing and treatment using the Swedish National Prostate Cancer Register. After calibration, we were able to closely match observed prostate cancer incidence trends in Sweden. Assuming that patients detected at an earlier stage by screening receive a commensurate survival improvement, we find that the calibrated model replicates the observed mortality reduction in a simulation of ERSPC. Using the resulting model, we predicted incidence and mortality following the introduction of regular testing. Compared with a model of the current testing pattern, organised 8 yearly testing for men aged 55–69 years was predicted to reduce prostate cancer incidence by 14% and increase prostate cancer mortality by 2%. The model is open source and suitable for planning for effective prostate cancer screening into the future.

TGF-BETA IN THE NATURAL HISTORY OF PROSTATE CANCER.

SUMMARYAll transforming growth factors beta (TGFß) are cytokines that regulate several cellular functions such as cell growth, differentiation and motility. They may also have a role in immunosuppression. Their role is important for normal prostate development. TGFß is active in the regulation of balance between epithelial cell proliferation and apoptosis through stromal epithelia via the androgen receptor action. TGFß protects and maintains prostate stem cells, an important population necessary for prostate tissue regeneration. However, TGFß is shown to have a contrasting role in prostate tumor genesis. In the early stages of tumor development, TGFß acts as a tumor suppressor, whereas in the later stages, TGFß becomes a tumor promoter by inducing proliferation, invasion and metastasis. In this review, we outline complex interactions that TGFß-mediated signaling has on prostate tumor genesis, focusing on the role of these interactions during the course of prostate cancer and, in particular, during disease progression.

Focal therapy of prostate cancer

The aim of this study was to summarize the latest evidence, as well as the rationale behind using focal therapy for the treatment of prostate cancer. With patients becoming more educated, knowledge of the available evidence is key when discussing treatment. In older works, the natural history of prostate cancer has been described as being multifocal, driven by one index lesion. This represents the key argument for most experts, why focal therapy is feasible in prostate cancer. Most modalities have similar results. For high-intensity focussed ultrasound (HIFU), a pooled data analysis with a median follow-up of 2.2 years showed a negative biopsy rate of 77% with a salvage therapy free rate of 92%. A matched pair analysis comparing irreversible electroporation with robot-assisted radical prostatectomy showed a better side effect profile for focal therapy in evenly matched groups, yet with worse disease-free survival. Interestingly, the better outcomes concerning continence and erectile function did not translate into better patient-reported outcomes. Focal therapy modalities are generally well tolerated and show good results in terms of continence and potency. Long-term follow-up is not available, and inclusion criteria for trials are not yet uniform. Newer technologies, such as photodynamic therapy, are being developed, as well as improvements to older techniques, such as HIFU.

Radiothérapie du cancer de la prostate localisé chez le sujet âgé : l’hypofractionnement modéré est-il le traitement de référence ?

Radiation therapy technique and schedules could be adapted to patient's age because of a natural history of prostate cancer perceived as different, taking into account the comorbidities of patients but also a particular tolerance of elderly subjects. Thus, in localized prostate cancer, evaluation of associated diseases is essential before considering a treatment that will be of interest only if the life expectancy is greater than 10 years. When a curative approach is decided, radiotherapy holds a place of choice. Due to the recent results of randomized studies evaluating moderate hypofractionnated radiotherapy, showing a carcinological equivalence compared to a standard fractionation, this reduction in the duration of treatment appears particularly indicated in this elderly population. This approach permits to maintain the quality of life of patients, potentially with lower costs for society. The purpose of this article is to present the results of randomized trials of moderate hypofractionnation and discuss their application in the population of elderly patients with localized prostate cancer.

Abstract B026: Axl may support dormancy of disseminated tumor cells by inducing cell clustering and decreasing proliferation of metastatic prostate cancer cells

Abstract While the majority of prostate cancer (PCa) patients are cured by radical prostatectomy and/or radiation, 10-15% of these men eventually develop recurrent disease in the form of lethal metastases. The most common site for PCa metastasis is the bone marrow. The time from primary tumor removal to recurrence can range from 1-2 years to decades, and constitutes a period of minimal residual disease in which cancer cells remain in the body but are clinically undetectable. It is thought that these disseminated tumor cells (DTCs) are able to maintain a state of cellular dormancy in the bone marrow in which they are not proliferating or dying, and may be the seeds for lethal metastases. By understanding the mechanism(s) that regulate dormancy, we may be able to prevent metastasis altogether. Our group has previously found that the secreted bone marrow factor Gas6 and the expression of its receptor Axl are associated with dormant DTCs in xenograft mouse models. Thus, we hypothesize that Gas6 signaling through Axl mediates dormancy. In this study, we sought to functionally support this hypothesis both in vitro and in human PCa tissue. Overexpression of Axl in the C42B PCa cell line decreased proliferation in vitro, and this was independent of Gas6 when Axl was highly overexpressed. Axl overexpression also led to aggregation of C42B cells, suggestive of a possible role in circulating tumor cell (CTC) clustering to survive the circulation and inhabit the bone marrow. Furthermore, immunohistochemical staining of a PCa tissue microarray showed almost no Axl positivity in cancer cells, regardless of Gleason score and other clinical outcomes. Negative staining was also observed in sections from liver, lymph node, and tibial metastases. Consistent with this, Axl expression correlates with decreased incidence of biochemical recurrence and increased overall survival in the GRID and TCGA databases, respectively. These results indicate an antiproliferative role for Axl in PCa, and suggest its temporal expression during the natural history of PCa. Ongoing work includes assessing the expression of Axl on patient CTCs and DTCs, and using xenograft mouse models of metastasis to analyze the effects of Axl overexpression and knockout in PCa cell lines. Citation Format: Haley D. Axelrod, Kenneth C. Valkenburg, Jessica L. Hicks, Angelo M. DeMarzo, Kenneth J. Pienta. Axl may support dormancy of disseminated tumor cells by inducing cell clustering and decreasing proliferation of metastatic prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B026.

The natural history of prostate cancer on MRI: lessons from an active surveillance cohort.

Multiparametric magnetic resonance imaging (mpMRI) is being used increasingly in the setting of active surveillance (AS) for prostate cancer. We investigated changes in the mpMRI appearance of lesions on AS, to show the variability of volume measurements in visible lesions and assess change in lesion size according to grade. We retrospectively retrieved 86 men on AS (NICE guidelines) with more than one mpMRI (the first before 2013). Two radiologists, in consensus, were blinded to patient demographics and date of scan. The scans were randomly reported to reduce any bias. For visible lesions, we measured volume by planimetry on the sequence best showing the most conspicuous (index) tumour and attributed a 5-point Likert score. 43/86 men did not have a visible lesion on the initial mpMRI (≤2/5). Of these, 5/43 had developed a lesion scoring ≥3/5 ata median of 3.6 years of follow up. 40/86 had a lesion scoring ≥3/5 on two or more scans. There was a significant increase in volume over 3.6 years by a median of 10% (p < 0.01)-by a median of 6% for Gleason 3+3 and 18% for 3+4 (p = 0.058). Thirty-five men had a visible lesion on two scans separated by <2 years; of these, 21/35 showed a 78% median increase in tumour size between the two scans and 11/35 showed an apparent 25% median decrease in lesion size. A total of 17% of men with no visible lesion developed a visible lesion at a median follow up of 3.6 years. It is possible to show significant growth in patients with a visible lesion, but variability in volume measurements between scans means that it is difficult to reliably detect increases of this order. This variability may inform the design of mpMRI protocols in AS and the time between follow up scans.

Optimal Management of Prostate Cancer Based on its Natural Clinical History.

Prostate cancer is the most common malignancy in males and, despite a marked improvement in diagnostic techniques, a not small percentage of prostate tumours is still diagnosed in advanced stage. It is now clear that prostate cancer passes through distinct phases during its natural history, starting from an initial phase, in which the disease has a locoregional extent, until a very late phase when it becomes refractory to hormone therapy. It is important to distinguish between local disease, in which tumor may be considered localized in the gland and a systemic disease characterized by high tumor burden and/or dissemination of circulating tumour cells. All the prostate cancers, at first diagnosis, are characterized by high sensitivity to the androgen deprivation therapy (ADT); however, during the natural history, after a variable period, they become castration resistant. In the past, few therapy options were available for castration resistant prostate cancer, while at present much more approaches can be employed, both hormone-based therapies and chemotherapy regimens. Hypercastration agents are defined as drugs capable to target the androgenandrogen receptor axis even in castrate resistant conditions. Abiraterone and enzalutamide are the only two hypercastration agents available for clinical use. Osteoclast targeted agents, such as zoledronic acid and denosumab can always been employed, but their use should be limited to the castrate resistant setting. The optimal understanding of all phases characterizing the natural history of prostate cancer may certainly be useful for the selection of the best therapeutic options in prostate cancer.

Nuclear Medicine in Prostate Cancer: A New Era for Radiotracers.

Natural history of prostate cancer (PCa) is extremely variable, as it ranges from indolent and slow growing tumors to highly aggressive histotypes. Genetic background and environmental factors co-operate to the genesis and clinical manifestation of the tumor and include among the others race, family, specific gene variants (i.e., BRCA1 and BRCA2 mutations), acute and chronic inflammation, infections, diet and drugs. In this scenario, remaining actual the clinical interest of bone scan (BS) in detecting skeletal metastases, an important role in diagnostic imaging may be also carried out by, positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI), which combine morphological information provided by CT and MRI with functional and metabolic data provided by PET acquisitions. With respect to PET radiotracers, being ancillary the usefulness of F-18 fluoro-deoxyglucose and not yet demonstrated the cost-effectiveness of F-18 Fluoride respect to BS, the main role is now played by choline derivatives, in particular by 11C-choline and 18F-fluorocholine. More recently, a greater interest for both diagnostic and therapeutic purposes has been associated with radiotracers directed to prostate-specific membrane antigen (PSMA), a transmembrane protein expressed on the cell surface, which showed high selective expression in PCa, metastatic lymph nodes and bone metastases. Several PSMA-targeted PET tracers have been developed many of which showing promising results for accurate diagnosis and staging of primary PCa and re-staging after biochemical recurrence, even in case of low prostate specific antigen values. In particular, the most widely used PSMA ligand for PET imaging is a 68Ga-labelled PSMA inhibitor, 68Ga-PSMA-HBED-CC (68Ga-PSMA-11). 99mTc-HYNIC-Glu-Urea-A for single photon emission computed tomography, and 177Lu-PSMA-617 for radioligand therapy has also been applied in humans, with interesting preliminary results related to a possible theranostic approach. A potential role of PSMA radioligands in radio-guided surgery has also been proposed.

The somatic clinico-genomics of localized, non-indolent prostate cancer

Prostate cancer is the second most frequently diagnosed non-skin male malignancy worldwide, with over 1.1 million new diagnoses each year. Population screening based on serum prostate-specific antigen (PSA) has shifted the disease burden toward earlier stage, localized disease. However, clinical outcomes for localized prostate cancer are highly heterogeneous, despite the use of clinical prognostic factors (PSA, Gleason grade, and TNM stage). Recent advances in massively-parallel DNA sequencing and computational biology have permitted detailed genomic analyses of all major human cancer types, including prostate cancer. However, the long natural history of prostate cancer has largely precluded rapid translation of this knowledge into clinical practice. Herein, we provide a “state of the field” overview of prostate cancer genomics, with particular focus on localized, non-indolent disease. We discuss recurrent somatic aberrations, across multiple mutational classes, which characterize this disease state, and suggest strategies through which an improved understanding of these molecular aberrations may be utilized in the curative setting. Finally, we summarize the major outstanding questions in prostate cancer genomics, and discuss hypotheses and potential strategies to begin to address these questions.

Biochemical recurrence after radical prostatectomy: what does it mean?

ABSTRACTBackgroundRadical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM).Review designA simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy.ObjectiveTo provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM.

Germline BRCA mutation in male carriers-ripe for precision oncology?

Prostate cancer (PC) is one of the known heritable cancers with individual variations attributed to genetic factors. BRCA1 and BRCA2 are tumour suppressor genes with crucial roles in repairing DNA and thereby maintaining genomic integrity. Germline BRCA mutations predispose to multiple familial tumour types including PC. We performed a Pubmed database search along with review of reference lists from prominent articles to capture papers exploring the association between BRCA mtuations and prostate cancer risk and prognosis. Articles were retrieved until May 2017 and filtered for relevance, and publication type. We explored familial PC genetics; discussed the discovery and magnitude of the association between BRCA mutations and PC risk and outcome; examined implications of factoring BRCA mutations into PC screening; and discussed the rationale for chemoprevention in this high-risk population. We confirmed that BRCA1/2 mutations confer an up to 4.5-fold and 8.3-fold increased risk of PC, respectively. BRCA2 mutations are associated with an increased risk of high-grade disease, progression to metastatic castration-resistant disease, and 5-year cancer-specific survival rates of 50 to 60%. Despite the growing body of research on DNA repair genes, deeper analysis is needed to understand the aetiological role of germline BRCA mutations in the natural history of PC. There is a need for awareness to screen for this marker of PC risk. There is similarly an opportunity for structured PC screening programs for BRCA mutation carriers. Finally, further research is required to identify potential chemopreventive strategies for this high-risk subgroup.

Definitive Radiotherapy for Older Patients with Prostate Cancer: Experience of a Medical Center in Taiwan

Whether age predicts treatment outcome of prostate cancer remains controversial. With the aging of the world population, properly understanding the effect of age may facilitate both treatment decision-making and defining the natural history of prostate cancer. Consecutive 581 patients with locally-confined adenocarcinoma of the prostate who received radical definitive radiotherapy(RT) (76–78 Gy) between 2004 and 2015 at a medical center in Taiwan were reviewed retrospectively. Median age was 78 years. The median follow-up was 66 months. The 5-year biochemical failure-free survival(BFFS), distant metastasis-free survival(DMFS), disease-specific survival(DSS), and overall survival(OS) rates were 84.9%, 93.8%, 97.8%, and 86.6%, respectively, for all patients. Comparing those above and below the age of 80, no difference in 5-year BFFS, DMFS, or DSS was found. Multivariate Cox regression analysis showed that tumor stage, Gleason score, initial PSA, and latency before RT were significant risk factors of BFFS. The latency before RT was significantly longer in the older group than in the under 80 group. Delay to start RT might explain the previous finding of inferior disease control in older patients in other studies. With the exception of OS, no other differences in outcomes or toxicities were observed in older patients.