Low-risk Localized Prostate Cancer Research Articles

A Single Institution’s Experience with Prostate Brachytherapy Seed Implants (1999-2009): Sexual Health Outcomes with and without Dose Escalation to Biologic Target Volumes

To evaluate sexual health outcomes following interstitial brachytherapy seed implant (SI) in a cohort of sexually active men treated for low-risk localized prostate cancer, for comparison of erectile dysfunction (ED) across two treatment methods: conventional peripheral loading versus with dose escalation to SPECT/CT defined biologic target volumes; a 10-year treatment history.

Long Term Outcomes of a Novel Five Fraction Hypofractionated Protocol for Low Risk Prostate Cancer

Extreme hypofractionation for prostate cancer is the delivery of large doses of radiation ( > 5 Gy) in a few fractions. The potential advantages of an extreme hyprofractionated regime are improved tumour control, minimal acute and late toxicities, and decreased treatment visits. We report the long term toxicities, biochemical and pathological outcomes of a prospective trial of low risk prostate cancer treated with a five fraction hypofractionated radiotherapy regime. A phase I/II study in which patients with low risk localized prostate cancer received 35 Gy in 5 fractions, once a week over 29 days. Treatment was delivered on standard linear accelerators with intensity modulated radiotherapy (IMRT) using daily imaging guidance and gold seed fiducial markers. Post-treatment long term follow up occurred every 6 months up to 5 years. Late toxicity was scored using Radiation Therapy Oncology Group (RTOG) late morbidity scoring criteria. Biochemical control (BC) was defined by the Phoenix definition (nadir + 2 ng/ml). Post-treatment biopsies were obtained at 3 years. As of May 2012, 84 patients have completed treatment with a median follow-up of 50 months (range 12 - 60 months). Median age was 67 years and median baseline PSA was 5.3 ng/ml. The following long term toxicities were observed: Grade 2: 4.7% GI, 4.7% GU, Grade 3+: 1% GI, 1% GU. Biochemical control was observed in 98% of patients. The one patient who has biochemical failure has a history of prostatitis and has a reported negative biopsy. Ninety-six percent were biopsy negative post-treatment. This novel technique of delivering a five fraction extreme hypofractionated schedule of radiotherapy is feasible, well tolerated and shows excellent pathologic and biochemical control for early risk prostate cancer.

Predictors of Health-related Quality of Life and Adjustment to Prostate Cancer During Active Surveillance

BackgroundActive surveillance (AS) is emerging as an alternative approach to limit the risk of overtreatment and impairment of quality of life (QoL) in patients with low-risk localised prostate cancer. Although most patients report high levels of QoL, some men may be distressed by the idea of living with untreated cancer. ObjectiveTo identify factors associated with poor QoL during AS. Design, setting, and participantsBetween September 2007 and March 2012, 103 patients participated in the Prostate Cancer Research International Active Surveillance (PRIAS) QoL study. Mental health (Symptom Checklist-90), demographic, clinical, and decisional data were assessed at entrance in AS. Health-related QoL (HRQoL) Functional Assessment of Cancer Therapy-Prostate version and Mini-Mental Adjustment to Cancer outcomes were assessed after 10 mo of AS. Outcome measurements and statistical analysisMultivariate logistic regression models were used to identify predictors of low (<25th percentile) HRQoL, adjustment to cancer, and a global QoL index at 10 mo after enrolment. Results and limitationsThe mean age of the study patients was 67 yr (standard deviation: ±7 yr). Lack of partner (odds ratio [OR]: 0.08; p=0.009) and impaired mental health (OR: 1.2, p=0.1) were associated with low HRQoL (p=0.006; area under the curve [AUC]: 0.72). The maladaptive adjustment to cancer (p=0.047; AUC: 0.60) could be predicted by recent diagnosis (OR: 3.3; p=0.072). Poor global QoL (overall p=0.02; AUC: 0.85) was predicted by impaired mental health (OR: 1.16; p=0.070) and time from diagnosis to enrolment in AS <5 mo (OR: 5.52; p=0.009). Influence of different physicians on the choice of AS (OR: 0.17; p=0.044), presence of a partner (OR: 0.22; p=0.065), and diagnostic biopsy with >18 core specimens (OR: 0.89; p=0.029) were predictors of better QoL. Limitations of this study were the small sample size and the lack of a control group. ConclusionsFactors predicting poor QoL were lack of a partner, impaired mental health, recent diagnosis, influence of clinicians and lower number of core samples taken at diagnostic biopsy. Educational support from physicians and emotional/social support should be promoted in some cases to prevent poor QoL.

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) in Perspective

Low risk localised prostate cancer may be able to be observed rather than treated according to the Prostate Cancer Intervention Versus Observation Trial (PIVOT). This review summarises the key issues surrounding the debate in the management of localised prostate cancer, and contextualises the PIVOT’s contribution.

Transperineal Implementation of Biocompatible Balloon in Patients Treated With Radiotherapy for Prostate Carcinoma: Feasibility and Quality Assurance Study in Terms of Anatomical Stabilization Using Image Registration Techniques

The purpose of this study was to evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace®) as well as the quality assurance of the procedure in terms of anatomical stabilization of the implant and reproductivity of treatment parameters during radiation therapy. Between December 2011 and February 2012, ten patients diagnosed with localized low risk prostate cancer, GS <7, PSA <10, cT1-2, were treated with external three dimensional conformal radiation therapy (3DCRT). Before the initiation of treatment, the Prospace® balloon was implanted by a minimally invasive procedure, though the perineum in the intermediate space between the rectum and the prostate. All patients underwent 3DCRT with 76-78 Gy in 38-39 daily fractions (2.0 Gy/ fraction). We evaluated the implant stabilization by examining by Computed Tomography its position right after implantation and three weeks after initiation of treatment, by using non-rigid registration technique. We also evaluated the acute toxicity according to EORTC/RTOG radiation toxicity criteria and also according to Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy, as well as pain related to Prospace implementation according to Visual Analogue Score (VAS). By using registration techniques, the Prospace device was found stable in sequential CTs with x,y,z-axis displacements up to 2.1 mm, 3 mm and 2.2 mm, respectively. The mean VAS score related to Prospace was 1.4(± 0.5) and the mean score of rectal toxicity according to S-RS score was 1.9(± 0.6). The implementation of PROSPACE is feasible. Implant’s position is relative stable. The procedure is minimally invasive with no recorded side effects. The incidence of patient-reported acute Gastrointestinal (GI) and Genitourinary (GU) toxicity as well as findings from flexible rectosigmoidoscopy, following high dose of 3DCRT after the prospace implantation, were low. The study is on-going and further results with analyzed data from more patients will be reported.

Presenting Treatment Options to Men with Clinically Localized Prostate Cancer: The Acceptability of Active Surveillance/Monitoring

Presenting treatment options to men with localized prostate cancer is difficult because of the lack of definitive evidence and the range of treatment options available. Active surveillance and monitoring programs are now a recognized treatment option for men with low-risk localized prostate cancer, but many patients are not fully aware of the details of such programs, and most still opt for immediate radical (surgery or radiotherapy) treatment. The provision of high-quality information with decision aids has been shown to increase the acceptability of active surveillance/monitoring programs. This chapter outlines techniques for providing high-quality information about active surveillance/monitoring, based on the findings of a randomized controlled trial of treatments for localized prostate cancer. The ProtecT (Prostate testing for cancer and Treatment) trial has randomized over 1500 men between active monitoring, radical surgery, and radical radiotherapy by ensuring that information was tailored to men's existing knowledge and views. Care was taken with the content, order, and enthusiasm of the presentation of treatments by recruitment staff, and clinicians and other health professionals were supported to feel comfortable with being open about the uncertainties in the evidence and helped to rephrase terminology likely to be misinterpreted by patients. These techniques of information provision should be added to the use of decision aids to enable patients diagnosed with clinically localized prostate cancer in routine practice to reach well-informed and reasoned decisions about their treatment, including full consideration of active surveillance and monitoring programs.

Changes in apparent diffusion coefficient and T2 relaxation during radiotherapy for prostate cancer

To evaluate regional and temporal changes in apparent diffusion coefficient (ADC) and T2 relaxation during radiation therapy (RT) in patients with low and intermediate risk localized prostate cancer. Seventeen patients enrolled on a prospective clinical trial where MRI was acquired every 2 weeks throughout eight weeks of image-guided prostate IMRT (78 Gy/39 fractions). ADC and T2 quantification used entire prostate, central gland, benign peripheral zone, and tumor-dense regions-of-interest, and mean values were evaluated for common response trends. Overall, the RT responses were greater than volunteer measurement repeatability, and week 6 appeared to be an optimum time-point for early detection. RT effects on the entire prostate were best detected using ADC (5-7% by week 2, P < 0.0125), effects on peripheral zone were best detected using T2 (19% reduction at week 6; P = 0.004) and effects on tumors were best detected using ADC (14% elevation at week 6; P = 0.004). ADC and T2 may be candidate biomarkers of early response to RT warranting further investigation against clinical outcomes.

Nasty or Nice? Findings from a UK Survey to Evaluate the Impact of the National Institute for Health and Clinical Excellence (NICE) Clinical Guidelines on the Management of Prostate Cancer

AimsAlthough the National Institute for Health and Clinical Excellence clinical guideline 58 (CG58) for prostate cancer management was expected to have a positive effect, several recommendations raised concern among UK physicians. We conducted a survey of UK oncologists in 2008 and a second, similar survey in 2010 to assess views on these recommendations and to evaluate the change in opinion over time. Materials and methodsTwo semi-structured questionnaires were issued by the British Uro-oncology Group to society members in September 2008 and October 2010. ResultsIn 2008, 61 UK oncologists completed the survey; 60% agreed that CG58 would make a positive contribution towards improving patient care. There was strong opposition towards active surveillance as the first-line treatment for men with low-risk localised prostate cancer (49% disagreement); implementing 5 yearly flexible sigmoidoscopy post-prostate radiotherapy (51% disagreement); offering follow-up outside of the hospital (e.g. by general practitioners in primary care) for men with a stable prostate-specific antigen for ≥2 years (44% disagreement); and recommendations against docetaxel retreatment (47% disagreement) or bisphosphonate use (58% disagreement). In 2010, 77 UK oncologists completed the survey. The results were largely consistent with 2008, although several recommendations, particularly for localised disease, seem to have promoted a change in clinical practice, suggesting that they are facilitating a standardised approach. Compared with 2008, the 2010 results indicate a shift in favour of active surveillance (80% agreement) and primary care follow-up (59% agreement), but increasing opposition for docetaxel retreatment (57% disagreement). Opinions remained divided for flexible sigmoidoscopy and bisphosphonates. ConclusionsDespite initial concerns, the CG58 seems to have had a positive impact on prostate cancer management in the UK, with adherence likely facilitating a standardised approach. However, with new data emerging, these findings underscore the need to regularly update guidelines. A revision of the CG58 is anticipated by 2014.

Initial Brazilian experience in the treatment of localized prostate cancer using a new generation cryotechnology: feasibility study

The objective of our study is to present the first Brazilian cryoablation experience in the treatment of low and intermediate risk localized prostate cancer using 3rd generation cryoablation and real-time biplanar transrectal ultrasonography. Ten Brazilian patients underwent primary cryoablation for localized prostate cancer between October 2010 and June 2011. All patients consented for whole gland primary cryotherapy. The procedures were performed by 3rd generation cryoablation with the Cryocare System ® (Endocare, Irvine, California). Preoperative data collection included patient demographics along with prostate gland size, Gleason score, serum prostate specific antigen, and erectile function status. Operative and post--operative assessment involved estimated blood loss, operative time, complications, serum PSA level, erectile function status, urinary incontinence, biochemical disease free survival (BDFS), and follow-up time. All patients in the study successfully underwent whole gland cryoablation. The mean of: age, prostate size, PSA level, and Gleason score, was 66.2 years old; 40.7 g; 7.8 ng/mL; and 6 respectively. All patients were classified as low or moderate D' Amico risk (5 low and 5 moderate). Erectile dysfunction was present in 50% of patients. The estimated blood loss was minimal, operative time was 46.1 minutes. All patients that developed erectile dysfunction post-treatment responded to oral or intracavernosal medications with early penile rehabilitation. All patients maintained urinary continence by the end of a 10 months evaluation period and none had biochemical relapse within the mean follow-up of 13 months (7-15 months). Our initial experience shows that cryoablation is a minimally invasive option for the treatment of localized prostate cancer. Short term data seems to be promising but longer follow-up is necessary to verify oncological and functional results.

Secondary chemoprevention using short period (3 months) of LHRHa as an option for men with low-risk localized prostate cancer (LRPC) before active surveillance (AS).

e15105 Background: Definition of LRPC and candidates for AS remains problematic. Relevant markers that reflect tumor aggressiveness are still to be determined. When AS is used it can be difficult to assess disease progression despite surveillance with PSA and repeat biopsies. Moreover, 20-50% of patients on AS were over the windows of curability when radical treatment was triggered. The current knowledge of PC suggests that aggressiveness should be assessed not only in terms of clinical features but also in terms of response to Androgen Deprivation Therapy (ADT). Methods: 83 men with LRPC (T1c or T2a PC; PSA ≤10ng/ml; Gleason score ≤6) whom have chosen prostate cancer management without radical therapy were included. They then underwent AS after receiving one injection of ELIGARD-22.5. AS consisted of PSA every 3 months (mo) and biopsies (≥12 cores) every 12mo. Patients were stratified at diagnosis according to age at diagnosis, PSA, PSA density, PSA nadir, bio-testosterone, dynamic MRI staging, % positive cores and length of tumor on the diagnosis biopsy. Predictive factors of recurrent PC observed on biopsy were tested using a Cox regression and Markov models. Results: Mean age at diagnosis of LRPC was 64 years, (standard deviation, 6.2 years). Median time to follow-up after diagnosis biopsy was 31mo. Surveillance biopsies were positive for 37 men (44%) (7 with Gleason score&gt;6). In the subgroup of insignificant PC according EPSTEIN criteria surveillance biopsies were positives for 17/48 men (35%) (2 with Gleason score&gt;6). Expected results from literature on classical AS were 60-70% of positive biopsy and 10-21% of upgraded biopsy at the first repeat biopsy. Predictive factors of prostate cancer observed on biopsy were: PSA nadir at 3mo &lt;0,1ng/ml (OR=1.8; 95%CI 1.0 to 3.3 p=0.04), positive core biopsy&gt;1(OR=1.7; 95%CI 1.0 to 2.9; p=0,03), and &gt;T1c detectable tumor on MRI (OR=2.9; 95%CI 1.4 to 5.9; p=0.003). Conclusions: Results obtained with 3mo of LHRHa for LRPC suggest that ADT response can be used firstly to reduce prevalence of primary PC lesions and secondly in order to identify PC able to castration resistance and consequently which require radical treatment.

Biochemical survival and morbidity of high-intensity focused ultrasound (HIFU) as a primary monotherapy for low-risk localized prostate cancer: Outcomes from the @-registry following the ENLIGHT trial inclusion criteria.

e15194 Background: Prostate Cancer (PCa) HIFU (Ablatherm, EDAP-TMS, Lyon, France) is currently under investigation in the US. This study reports biochemical, biopsy and morbidity outcomes for a population of low risk localized PCa patients meeting ENLIGHT FDA trial inclusion criteria. These data were accrued from European HIFU centers using an online HIFU database (@-Registry) . Methods: The patient’s selection criteria for this study were: low risk prostate cancer patients (T1c to T2a, PSA&lt;10ng/ml, Gleason≤6), with a prostate A-P diameter and volume of &lt;25mm and &lt;40cc, and no pre-treatment hormone therapy. Kaplan-Meier analysis was performed to determine biochemical survival with failure defined as the Phoenix definition (PSA nadir+2). Morbidity data, need for salvage treatment and biopsy data were analyzed. Results: From 12 European centers, 358 men met the inclusion criteria. The baseline mean age, PSA and median Gleason sum were 69.7±6.4 years, 5.8±2.4 ng/ml and 6, respectively. Stage was 65.9% T1c and 34.1% T2a. Patients were followed for 6.6±3.1 years (range: 0.6 to 18 years). Median PSA nadir was 0.09 which was reached 13.9±10.7 weeks after HIFU. The salvage treatment rate was 8.7%, and the negative biopsy rate was 90.2% Actuarial BDFS at 5 and 10 years was 87% and 73% respectively. The morbidity data identified GradeI, II and III stress incontinence in 12.3%, 4.5% and 1.7% of the population, respectively. The Bladder Outlet Obstruction rate was 20.7% (urinary retention, urethral stenosis ). Urethro-rectal fistula was not observed. Conclusions: HIFU achieved good biochemical control at 10 years of follow-up for low riskPCa patients and negative biopsy rates were high. HIFU demonstrated an acceptable morbidity, especially with the lack of any serious events(specifically fistula). Bladder Outlet Obstruction was the most bothersome adverse event. HIFU appears as a valuable and safe therapy for long term low risk PCa treatment.

157 LONG-TERM OUTCOMES ACCORDING TO RISK CATEGORY OF PROSTATE CANCER IN A NATION-WIDE, POPULATION-BASED STUDY

You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History I1 Apr 2012157 LONG-TERM OUTCOMES ACCORDING TO RISK CATEGORY OF PROSTATE CANCER IN A NATION-WIDE, POPULATION-BASED STUDY Jennifer Rider, Fredrik Sandin, Katja Fall, and Pär Stattin Jennifer RiderJennifer Rider Boston, MA More articles by this author , Fredrik SandinFredrik Sandin Uppsala, Sweden More articles by this author , Katja FallKatja Fall Örebro, Sweden More articles by this author , and Pär StattinPär Stattin Umeå, Sweden More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.208AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are very limited data on long-term outcomes among men diagnosed with prostate cancer (PCa) from cohorts that incorporate information on risk categories. We aimed to separately assess death from PCa, cardiovascular disease (CVD), and other causes for men with PCa according to risk category defined by clinical stage, Gleason score and serum levels of PSA at diagnosis. METHODS We utilized a population-based cohort study of 117,328 PCa cases in the National Prostate Cancer Register (NPCR) of Sweden diagnosed between 1991-2009 categorized into five risk categories according to the National Comprehensive Cancer Network. The cumulative probability of death for up to 15 years of follow-up was estimated using a period analysis and by treating death from PCa, death from CVD, and death from other causes as competing events. Estimates were stratified by risk group and by age. The observed overall mortality was also compared to expected mortality as estimated by use of population death rates from the Swedish male population matched to the study population by age and calendar year. RESULTS As shown in Figure 1, the cumulative risk of death from PCa and other causes, respectively, at 15 years following diagnosis ranged from 7.2% (95% CI: 5.9-8.6%) and 38.6% (36.0-41.3%) for men with low-risk disease, to 68.9% (67.7-70.1%) and 28.1% (95% CI: 26.9-29.2%) for men presenting with distant metastases. At 15 years, CVD alone was responsible for the greatest proportion of deaths among PCa patients with low- and intermediate-risk disease. Regardless of age, observed mortality was no different than expected among men with localized low-risk PCa. Risk of excess mortality increased steadily with longer follow-up among men with localized intermediate-risk, localized high-risk, regionally metastatic, and metastatic disease at diagnosis. CONCLUSIONS The majority of deaths among men with localized disease - even disease considered high risk at diagnosis - are from causes other than PCa. Our results not only highlight the need for more refined tools for PCa diagnosis and therapeutic selection, but also demonstrate the importance of strategies to reduce CVD and other preventable causes of death among men with PCa. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e65 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jennifer Rider Boston, MA More articles by this author Fredrik Sandin Uppsala, Sweden More articles by this author Katja Fall Örebro, Sweden More articles by this author Pär Stattin Umeå, Sweden More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Biochemical, pathologic, toxicity, and quality-of-life outcomes in a five-fraction hypofractionated accelerated radiotherapy treatment using standard linear accelerators and gold seed fiducials.

186 Background: Biological dose escalation through hypofractionated image-guided radiotherapy (H-IGRT) holds the promise of improved patient outcomes, system capacity but decreased cost. In 2006 we initiated a prospective trial of H-IGRT of patients with low risk localized prostate cancer. In this report, we report the toxicities, quality of life (QOL), biochemical and pathologic outcomes of this cohort with more mature follow-up. Methods: A phase I/II study in which patients with T1-2b, Gleason≤6, and PSA≤10 ng/ml prostate cancer received 35 Gy in 5 fractions, once a week over 29 days. No patients received hormone therapy. Treatment was delivered with intensity modulated radiotherapy (IMRT) on standard linear accelerators, with daily image guidance using gold seed fiducials, and a 4 mm CTV-PTV margin. CTCAE v3.0 and RTOG late morbidity scores were used to assess acute and late toxicities, respectively. QOL was assessed by the Expanded Prostate Cancer Index Composite (EPIC). Biochemical control (BC) was defined by the Phoenix definition, adjusted for benign bounce. Results: As of September 2011, 83 patients have completed treatment with a median follow-up of 42 months (range 12–60 months). Median age was 67y (42 – 82y). 78 patients (92%) were T1a-c; all had Gleason 6 cancers; median PSA was 5.3 (0.8 – 9.9 ng/ml). 82 (99%) had BC; the remaining patient had a negative biopsy and a history of chronic prostatitis. The median PSA on last visit was 0.69 ng/ml (.02 – 2.6 ng/ml). Of 59 patients who have had a biopsy to date, 2 (3%) were positive but both are under BC. The following toxicities were observed: acute grade 3+: 0% GI, 1% GU, 0% fatigue; late grade 3+: 1% GI, 1% GU. Median transformed QOL scores at baseline (0.5 SD) and 36mo follow-up are: urinary – 95% (4.1), 93%; bowel – 96% (4.8), 96%; sexual – 65% (13.7), 51%; and hormonal – 95% (5.3), 95%. Conclusions: This novel technique employing standard linear accelerators to deliver an extreme hypofractionated schedule of radiotherapy is feasible, well tolerated and shows excellent pathologic and biochemical control. A randomized study versus standard fractionation should be performed.

Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient's quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted photodynamic therapy (VTP). Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities.

21 The impact of preoperative factors on positive surgical margin after robotic radical prostatectomy in low-risk localised prostate cancer

21 The impact of preoperative factors on positive surgical margin after robotic radical prostatectomy in low-risk localised prostate cancer

POD-07.08 Morbidity of High Intensity Focused Ultrasound (HIFU) as a Primary Monotherapy for Low-Risk Localized Prostate Cancer: Outcomes from the ENLIGHT Trial

Prostate HIFU is currently under investigation under an FDA granted Investigational Device Exemption. Herein we report the morbidity profile observed during the ENLIGHT Trial of primary HIFU performed as a monotherapy. Traditional morbidities of incontinence, stricture and erectile dysfunction and bowel injury were evaluated prospectively as a component of the trial.

Focal Therapy is an Option for the Majority of Localised Prostate Cancers: A Histopathological Study of Contemporary UK Radical Prostatectomies

Objectives: Focal therapy for prostate cancer offers a management option intermediate between active surveillance and radical therapy for small volume, low grade localised prostate cancer. We studied a series of UK radical prostatectomies (RP) performed for organ-confined prostate cancer to identify the proportion of cases potentially suitable for pure lesion only focal therapy (PLFT) or focal hemi-gland ablation (FHA). Methods: The pathological features of 309 RP specimens were studied. Patients were grouped into the following categories: group A: unifocal cancer; group B: multifocal disease where only the index cancer was significant (Epstein's criteria); group C: unilateral multifocal significant disease; group D: bilateral multifocal significant disease. Results: 56% (172) patients were candidates for PLFT, including 70 group A cases plus 102 group B cases. Group C comprised 4% (11) cases who are candidates for FHA. Thus 60% (183) cases were candidates for either PLFT or FHA. Conclusions: A significant number of patients are potential candidates for focal therapy in this RP series. We encourage prospective clinical trials investigating the oncological safety and outcomes of focal therapy in treating low and intermediate risk localised prostate cancer.

Stereotactic body radiation therapy: an emerging technique for prostate cancer treatment

AbstractPurpose: Stereotactic Body Radiation Therapy (SBRT) is treatment using stereotactic techniques outside of the brain. SBRT involves accurate delivery of an extremely hypofractionated treatment which should be beneficial for tumours with a low α/β ratio. The focus of the review is on low risk localised prostate cancer due to the low α/β ratio and lack of research into the region. This will help to determine if further research into SBRT for prostate cancer is warranted. Methods: A review of the literature was performed to discover the history and current use of SBRT for various body sites. Results: SBRT has been investigated for lung and liver cancers with studies finding toxicity and survival outcomes equivalent to conventional radiation therapy. Research into the use of SBRT in other body sites has also been conducted. However, short follow up times, small patient populations and lack of randomised trials mean the results are not of the highest reliability. The same limitations are true of studies examining SBRT for prostate cancer. Despite these limitations, positive acute toxicity and survival outcomes were observed across five studies into SBRT for prostate cancer. Conclusion: There has been no published study into the use of SBRT for prostate cancer within Australia. Theoretical modelling suggests prostate cancer will respond well to the hypofractionated treatment provided by SBRT. Good clinical outcomes with reduced treatment times are possible with SBRT making it a more convenient treatment option for the patient. SBRT also allows greater patient throughput in radiation oncology departments.

Active surveillance for low-risk prostate cancer: an update

Active surveillance is now an accepted management strategy for men with low-risk localized prostate cancer, in recognition of the knowledge that the majority of men with such cancers are likely to die from other causes. The most obvious benefit of active surveillance is the reduction of morbidity associated with surgery by delaying or avoiding radical gland therapy. Other advantages include lower overall costs to the health-care system and potentially a better quality of life. These advantages should be balanced against the risks of delayed therapy, the most considerable of which being development of more-aggressive disease. Appropriate selection criteria and the definition of triggers for intervention with radical therapy are critical components of an active surveillance protocol. The ability to accurately identify and cure the men whose cancers will progress using clinical, biopsy and imaging data is yet to be resolved, as is the psychological burden of living with an untreated cancer. The benefit of 5α-reductase inhibitors as secondary chemoprevention in men on active surveillance is a new avenue of research. Focal therapy, which has the similar aim of reducing morbidity while maintaining oncological control, is an emerging competitor for active surveillance. Nevertheless, active surveillance is an appealing management option for selected men with prostate cancer.

Pathologic outcomes in patients with clinically low-risk prostate cancer deemed eligible for active surveillance.

110 Background: Active surveillance (AS) is becoming increasingly popular as a treatment option for men with clinically localized low-risk prostate cancer. Gleason score ≤ 6 and clinical stage ≤ T2a are selection criteria for AS. However, Gleason upgrading or upstaging from the diagnostic biopsy to the surgical specimen is not uncommon. We thus sought to identify risk factors that could more accurately predict Gleason upgrading and/or upstaging in AS-eligible men. Methods: 786 patients from our prospective database of 2,412 men who underwent robotic-assisted radical prostatectomy by a single surgeon from January 2005 to August 2010 would have fulfilled standard AS criteria (Gleason sum ≤ 6, clinical stage ≤T2a disease, PSA &lt;10ng/ml, &lt;3 positive cores and ≤50% cancer present in a single core). This formed the basis of our study cohort. Clinicopathologic parameters, including number of cores at initial biopsy, biopsy cancer volume, preoperative PSA, number of cancer-positive cores, body mass index, and prostate volume were recorded prospectively. Data were evaluated using chi- square and multivariate logistic regression analyses. Receiver operator characteristic curves (ROC) were constructed to determine the optimal cutoff values. Results: 320 of 786 AS-eligible patients (40.7%) had Gleason upgrading at final pathology following radical prostatectomy. Upstaging was present in 591 patients (75.1%). 626 patients (79.6%) had Gleason upgrading and/or upstaging. On univariate analysis, BMI, PSA density, preoperative PSA, lower prostate volume and maximum percentage of cancer in biopsy cores were predictors of Gleason upgrading and/or upstaging. On multivariate analysis, all variables, except for BMI and PSA density, lost statistical significance. PSA density &gt; 0.1 ng/ml/cm3 and BMI &gt;29 kg/m2 are the optimal cutoff values based on ROC analysis. Conclusions: PSA density and BMI are significant predictors of Gleason upgrading and/or upstaging, and should be incorporated into contemporary selection criteria for AS protocols. No significant financial relationships to disclose.