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Brachytherapy- State Of The Art Radiotherapy In Prostate Cancer
BJU International
Abstract
Contemporary treatment options for prostate cancer are considered to have comparable efficacy. Therefore other differences such as treatment related toxicities, impact on quality of life, convenience, treatment time, and cost become important considerations in influencing treatment choice. The goal of brachytherapy is to achieve high precision, targeted radiotherapy utilising advanced computerised treatment planning and image guided delivery systems to achieve tailored ablative tumour dose to the prostate whilst sparing surrounding organs at risk to minimise potential toxicities. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Supplementary resource (1)
Data
November 2015
... An enlarged prostate may also lead to pubic arch interference and difficulties in needle placement within the prostate gland. 8 Brachytherapy insertions are not recommended following a transurethral resection of the prostate within the previous three to six months, and may not be possible in men with a large resection cavity. Patients need to have acceptable anaesthetic risks for general or spinal anaesthesia and not have a bleeding disorder or current therapy with blood thinning agents. ...
... If, after the planning process, it becomes clear that this dose is not going to be deliverable due to misplacement or movement of seeds causing a low dose region, this could be rectified by either repeat seed insertion or an EBRT boost. 8 In HDR brachytherapy, a remote afterloading system using Ir 192 is used. Flexible, hollow afterloading applicator needles (usually 15-20 per patient) are positioned directly into the prostate gland through a perineal template using direct transrectal ultrasound guidance under general or spinal anaesthetic (Figure 3). ...
Brachytherapy for prostate cancer involves placing radioactive seeds directly into the prostate, with the aim of protecting healthy surrounding tissue. This article reviews the current indications for brachytherapy treatment and the different options available. The practicalities and potential complications of treatment are also considered.
... Both modalities can be used either as a monotherapy or as a boost with EBRT. Monotherapies are generally used for low-and intermediate-risk PC, whereas combined therapy usually is used for intermediate-and highrisk PC [66]. The logistics are the main advantage of LDR: you can implant it with small shields, whereas HDR is applied in a specialised shielded room for radioprotection issue. ...
... LDR is accomplished in an outpatient single visit setting. Individual (loose) seeds or stranded seeds (seeds linked together in dissolvable suture material) are used in LDR [66]. Stranded seeds minimise seed migration and improve dose delivery [68,69]. ...
Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together ( shared decision-making ) while using patient decision aids.
... Its aim is to develop an optical fibre-based in-vivo dosimeter for prostatic and gynecological brachytherapy (BT). Brachytherapy is a form of radiotherapy performed through the temporary or permanent implantation of -emitting seeds in the patient's body, that allows delivering the dose within the cancer volume and avoids undue exposure of nearby healthy organs [1,2]. In particular, BT can be divided into High Dose Rate (HDR, > 12 Gy/h) and Low Dose Rate (LDR, from 0.4 Gy/h to 2 Gy/h). ...
Brachytherapy is a radiotherapy procedure performed with radioactive sources implanted into the patient's body, close to the area affected by cancer. This is a reference procedure for the treatment of prostate and gynecologic cancer due to the reduction of the dose released close to organs at risk (e.g., rectum, bladder, colon). For this reason, real-time dose verification and source localisation are essential for an optimal treatment plan. The ORIGIN collaboration aims to achieve this goal through a 16-fibre sensor system, designed to house a small volume of scintillating material in a transparent fibre tip to enable point-like measurements. The selected scintillating materials feature a decay time of about 500 μs and the signal associated with the primary γ -ray interaction results in the emission of a sequence of single photons distributed over time. Therefore, the dosimeter requires a detector with single-photon sensitivity and a system designed to provide dose measurements by photon counting. Uniformity of fibre response, system stability and reproducibility of measurements are key features of the dosimeter. The characterisation of the 16-channel dosimeter system equipped with thermo-electrically cooled Silicon Photomultipliers, carried out in the laboratory using an X-ray cabinet, is discussed and the results are compared with an earlier version equipped with SiPMs operated at room temperature.
... Brachytherapy (BT) is a radiotherapy procedure during which radioactive sources, called seeds, are implanted into the patient's body, in or close to the tumour [1][2][3][4]. According to the average activity of the source, clinical treatments are categorized as either Low Dose Rate (LDR, in the 0.4-2 Gy/h range) or High Dose Rate (HDR, in excess of 12 Gy/h) [5]. ...
Source localisation and real-time dose verification are at the forefront of medical research in brachytherapy, an oncological radiotherapy procedure based on radioactive sources implanted in the patient body. The ORIGIN project aims to respond to this medical community’s need by targeting the development of a multi-point dose mapping system based on fibre sensors integrating a small volume of scintillating material into the tip and interfaced with silicon photomultipliers operated in counting mode. In this paper, a novel method for the selection of the optimal silicon photomultipliers to be used is presented, as well as a laboratory characterisation based on dosimetric figures of merit. More specifically, a technique exploiting the optical cross-talk to maintain the detector linearity in high-rate conditions is demonstrated. Lastly, it is shown that the ORIGIN system complies with the TG43-U1 protocol in high and low dose rate pre-clinical trials with actual brachytherapy sources, an essential requirement for assessing the proposed system as a dosimeter and comparing the performance of the system prototype against the ORIGIN project specifications.
... In terms of cost-effectiveness, HDR IRT was proven to be less expensive when compared to ERT 44 . ...
OBJECTIVE: The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation.
PATIENTS AND METHODS: We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk.
RESULTS: We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously.
CONCLUSIONS: We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.
... Lymphadenectomy costs were based on the CMS payment for the HCPCS code 38571 [22]. Brachytherapy costs were based on a study by Chao and colleagues [23]. Metastatic treatment costs were based on a ratio of total healthcare costs for local/regional to total metastatic healthcare costs per person as determined by the Medicare claims analysis. ...
Background: Current detection methodologies are often unable to identify the location and extent of recurrent prostate cancer (PCa) leading potentially to ‘futile’ local therapies in the presence of metastatic disease. The use of ¹⁸ F-fluciclovine PET/CT may lead to better patient management.
Objective: The aim of this study was to quantify the economic impact and cost–consequence of using ¹⁸ F-fluciclovine PET/CT in PCa recurrence.
Study design: A decision analytic model based on recurrent PCa imaging guidelines.
Setting: US hospital.
Participants: PCa patients experiencing biochemical recurrence.
Intervention: ¹⁸ F-fluciclovine PET/CT was compared to conventional imaging.
Main outcome measure: Budget impact, correct diagnoses, futile treatments, and cost-consequence (cost per correct diagnosis)
Results: For a hypothetical hospital serving 500,000 individuals, the model showed the use of ¹⁸ F-fluciclovine reduced ‘futile’ therapies by 19.2%. Re-imaging costs were reduced by 40.2% (31.2 to 30,673 (46.8%). When including subsequent 5-year patient management, the cost per ‘correct’ diagnosis declined $410,206 (49.2%).
Conclusion: ¹⁸ F-fluciclovine PET/CT imaging may improve the clinical management of men with recurrent PCa with minimal increase in healthcare spending.
... O objetivo da braquiterapiá e alcanar alta precisão, utilizando planejamento de tratamento computadorizado avançado e sistemas guiados por imagem para atingir uma dose elevada na próstata, enquanto osórgososórgos adjacentes são poupados para minimizar potenciais toxicidades. Duas técnicas distintas de braquiterapia podem ser usadas para tratar o CaP: braquiterapia por baixa taxa de dose (LDR), no qual as sementes radioativas são permanentemente implantadas no tecido da próstata ou braquiterapia de alta taxa de dose (HDR), em que a fonte radioativá e colocada temporariamente na próstata através de agulhas implantadas [4,5,6]. Quando comparado com a terapia de feixe externo e prostatectomia radical, a braquiterapia tem o controle do câncer e taxas de sobrevivência a longo prazo similares, com um risco reduzido de efeitos colaterais [7,8,9]. ...
One of the most advanced methods for the treatment of early-stage prostate cancer and brachytherapy, which uses 125 I-incorporated titanium metal seeds, which is radioactive, and is implanted in the prostate volume. In recent studies, we investigated the possibility of applying the Sol-Gel (SG) method for the production of bioactive seeds, incorporated with radioactive Sm in silica glasses for cancer treatment. In this project, three SiO 2 - CaO system glass compositions were synthesized using the SG method. The chemical and physical composition of the seeds were analyzed by X-ray Diffraction and Atomic Absorption Analysis. A pilot in vivo and in vitro toxicity study was conducted on rabbit and PC-3 strain cells. The results showed that the ceramic matrices in the SiO 2 - CaO - Sm system showed no toxicity in the in vivo model and no post-implant inflammatory process, no restriction to in vitro cell growth. In conclusion, there is no seed toxicity and radiotoxicity will only occur during the period when the seeds present activity from 153 Sm.
... One such custodian for urologists is the BJU International journal which centralises quality evidence-based urological knowledge. For example, this journal has key papers in the myriad of localised and systemic [13] treatment of prostate cancer, such as active surveillance [14], robotic prostatectomy [15], brachytherapy [16], and even alternative treatments like phytotherapy [17]. In the same way, reputable organisations can summarise evidence-based knowledge into a centralised online library in simple language so that our patients do not have to sift through the ocean of unsorted information on the Internet. ...
Introduction:
To compare (1) the quality of prostate cancer health information on the Internet, (2) the difference in quality between websites appearing earlier or later in the search, and (3) the sources of sponsorship for each of these websites.
Materials and methods:
The top 150 listed websites on the Google search engine for each of the 11 search terms related to prostate cancer were analysed. Quality was assessed on whether the website conforms to the principles of the Health On the Net Foundation. Each of these websites was then reviewed to determine the main source of sponsorship. Statistical analysis was performed to determine if the proportion of HON accreditation varied among the different cohorts of listed websites and among the 11 search terms used.
Results:
In total, 1650 websites were analysed. Among these, 10.5% websites were HON-accredited. The proportion of HON-accredited websites for individual search terms ranged from 3.3% to 19.3%. In comparison with the search term of "Prostate cancer," four search terms had statistically significant odds ratio of the rate of HON accreditation. Websites 51-150 were statistically less likely to have HON accreditation than websites 1-50. The top three website sponsors were journal/universities (28.8%), commercial (28.1%), and physician/surgeon (26.9%).
Conclusions:
The lack of validated and unbiased websites for prostate cancer is concerning especially with increasing use of the Internet for health information. Websites sponsored or managed by the government and national departments were most likely to provide impartial health information for prostate cancer. We need to help our patients identify valid and unbiased online health resources.
... Brachytherapy has been widely used for the treatment of localized prostate cancer with acceptable oncological outcomes and toxicity rates [122][123][124] . Radiotherapy techniques Radiofrequency ablation under TRUS guidance has been investigated in animal models of prostate cancer 132,133 . ...
Globally, the increased uptake of serum PSA level screening led to an increase in the number of diagnoses of low-risk and intermediate-risk prostate cancer. Traditionally, these patients have been considered for either active surveillance programmes or radical whole-gland therapies, such as prostatectomy or radiotherapy. Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue. This approach might result in reduced morbidity when compared with whole-gland therapies. In current practice, much controversy surrounds optimal patient selection and preoperative tumour localization strategies. Focal therapy modalities include cryotherapy, high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, radiofrequency ablation and focal brachytherapy. However, as long-term oncological data for focal therapies are lacking, formal recommendations for its use cannot be made.
... However, undesirable side effects of any radical procedure (surgery or radiation) including urinary incontinence, along with a rise in the uptake of active surveillance have led to their judicious use. Arguments for and against open and laparoscopic versus robotic-assisted radical prostatectomy (RARP) abound but some data suggest RARP may result in better early continence outcomes for men when compared with other approaches [1][2][3]. ...
The aim of the study was to evaluate the effect of pelvic floor muscle (PFM) assessment and training before and after robot-assisted laparoscopic radical prostatectomy (RARP) in improving PFM strength and urinary continence. We performed an analysis of a database of patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP) performed by two urologists from 2011 to 2013. Pelvic floor muscle (PFM) activation and strength were graded by a trained pelvic floor physiotherapist. Patients were given an exercise program, grouped according to the strength of their pelvic floor as graded by assessment, to complete before and after surgery. PFM strength was recorded preoperatively, 4 days post-catheter removal and 4 weeks post-catheter removal. Continence was recorded at 4 weeks postop and was defined as the requirement of no continence aids. A total of 98 patients had RARP and a preoperative physiotherapy assessment plus postoperative appointments at around 1 and 4 weeks post-RARP. The majority of men improved their PFM strength regardless of preoperative strength with no significant predictors of postoperative strength found. Age was the only significant predictor of postoperative incontinence. In this pilot study, a majority of patients increased their pelvic floor strength with time. Pelvic floor physiotherapy is an important modifiable patient factor, which does have an impact in improving patients’ urinary continence by strengthening the pelvic floor muscles. Patient age influences response to pelvic floor physiotherapy.
... As seen in our series, many men with biopsy Gleason 3 + 4 disease are offered radical surgery. An alternative is radiotherapy, with the options of external beam radiotherapy (EBRT) or brachytherapy [12]. Low dose rate brachytherapy can be used as monotherapy with 3 + 4 disease, particularly if only low-volume disease (percent cores involved <33%) is present. ...
Objective
To examine the feasibility of active surveillance for low volume Gleason sum (GS) 3 + 4 disease compared to GS 3 + 3 disease.
Patients and Methods
Retrospective review of 929 patients, with biopsy proven GS 3 + 3 and 3 + 4 PCa, undergoing upfront radical prostatectomy (RP) was performed. Suitability for AS was adapted from protocols by Royal Marsden Hospital, University of Toronto, and PRIAS by allowing Gleason 3 + 4 disease.
The outcomes assessed were adverse pathology at RP (upgrading ≥GS 4 + 3 and/or upstaging ≥pT3) and biochemical recurrence (BCR) after RP.
Results
Adverse pathology at RP was compared between GS 3 + 3 vs 3 + 4 groups. When selecting patients using Royal Marsden ( n = 714) or University of Toronto ( n = 699) protocols, there was statistically significantly more adverse pathology at RP in GS 3 + 4 group (21% vs 31%, P = 0.0028 and 19% vs 33%, P =<0.001 respectively). Using the more stringent PRIAS protocol ( n = 198), there was no statistical significant difference in groups.
There was no difference in BCR survival between biopsy GS 3 + 3 and 3 + 4 groups, regardless of which AS protocol assessed. Pre‐operative PSA and clinical staging were the predictors for BCR.
Conclusion
Presence of Gleason 3 + 4 at biopsy, when compared to 3 + 3, increases the risk of adverse pathology being present at radical prostatectomy for less stringent selection criteria. When considering AS, a stricter protocol such as PRIAS, limiting PSA density and number of positive cores to ≤2, appears to decrease the risk of adverse pathology. No differences in BCR were seen between biopsy 3 + 3 and 3 + 4 disease, regardless of AS selection criteria.
Flexible needles are navigated through anatomical pathways to reach deep seated tissues for minimally invasive surgical procedures. During such risky navigation, anatomical obstacles and the target malignant tissue regions could be dislodged due to excessive stress upon needle-tissue interaction. Hence, knowledge about the interactive forces is essential to execute a safe needle steering procedure during percutaneous cancerous treatments. This paper proposes an adaptive learning rate based multilayer perceptron technique for determining Young’s modulus of tissue at each stage of navigation and then utilizing this value to predict the deflection of flexible needle in tissue environment. To validate the accuracy of predictions, an energy-based model is incorporated into the analysis. Simulation results demonstrate that the proposed model can efficiently predict Young’s modulus in just 0.59 secs. To further validate the efficacy of this novel methodology, extensive experimental studies are conducted, including rigorous statistical analysis using ANOVA with a 5 % accuracy level. The effectiveness of neural networks is underscored through a two-sample t-test across 5 different trials, revealing consistently low mean absolute errors, typically below 1.5 kPa, except in trial 3. These findings highlight the reliability of the proposed novel technique in predicting Young’s modulus and ensuring accurate needle deflection predictions.
There has been a shift in recent years on the treatment of low- and intermediate-risk prostate cancer from the whole-gland prostatectomy or radiotherapy, in the attempt to avoid overtreatment of clinically insignificant disease and prevent unnecessary treatment-related side effects. Focal therapy for prostate cancer encompasses a few different modalities with the aim of targeting an ‘index lesion’ of cancer within the prostate, without having to perform radical whole-gland treatment, serving as a middle ground for patients who seek treatment, while minimising potential side effects by maintaining as much normal prostate tissue as possible. This chapter aims to summarise the published data on focal therapy, covering several modalities. It also addresses the published data and reviews on focal therapy for prostate cancer. PubMed, Google scholar, and Cochrane Library were searched, with emphasis on recent multicentre studies, examining the role for focal therapy, the index lesion, disease localisation, and a few focal ablation strategies. Cryotherapy, high-intensity focused ultrasound, laser ablation, irreversible electroporation and focal brachytherapy have all shown promising initial data as an alternative option to whole-gland therapy in intermediate-risk prostate cancer, with varying degrees of oncological effectiveness on failure-free survival/ re-treatment rates, and metastasis-free survival, as well as effects on urinary and sexual function. All modalities require further research into oncological effectiveness and safety. Focal therapy shows promise as a viable option for the treatment of carefully selected patients with well-defined intermediate-risk prostate cancer, although further research, clinical trials and long-term data is still required, and patients require close follow-up.
PURPOSE
To review common reported side effects and complications after primary LDR-BT (monotherapy) and discuss some of the technical aspects that could impact the treatment outcomes.
METHODS AND MATERIALS
A literature search was undertaken using medical subject headings (MeSH) complemented by the authors’ personal and institutional expertise.
RESULTS
The reported incidence of acute and late grade 2 or above urinary, bowel and sexual side effects is very variable across the literature. The learning curve and the implant quality have a clear impact on the toxicity outcomes. Being aware of some of the technical challenges encountered during the procedure and ways to mitigate them could decrease the incidence of side effects. Careful planning of seed placement and seed deposition allow sparing of the organs at risk and a lower incidence of urinary and gastro-intestinal toxicity.
CONCLUSIONS
Low dose-rate brachytherapy remains a standard monotherapy treatment in the setting of favorable-risk prostate cancer. High disease control and low long-term toxicities are achievable in expert hands with a good technique.
This research is motivated by the need of real-time needle tracking solutions in brachytherapy procedures for improving targeting accuracy. We compared two different modelling approaches to estimate brachytherapy 3D needle deflection during insertion into soft tissue from reaction forces and moments measured at the base of the needle: an analytical model based on beam deflection theory and, a data-driven model using a multilayer perceptron artificial neural network (ANN). Verification of the analytical model as well as training, validation, and testing of the ANN model were performed with experimental data obtained from over 120 insertion tests into gelatine tissue phantoms including a variety of needle types and tissue properties. The ANN model has lower prediction errors and is more robust to changes in testing conditions, with accurate predictions in 3 out of 4 tested scenarios; whereas the analytical model predictions are not statistically comparable to ground truth values in any of the tested scenarios. ANN models show a big potential for online 3D tracking of brachytherapy needles in a clinical context in comparison with beam theory analytical models. A simple neural network trained with numerous needle insertions into representative biological soft tissue could estimate needle tip position with submillimetre accuracy.
We present the concept of a new methodology to fast simulate the doses in brachytherapy with permanent implants, based on the knowledge of the seeds arrangement, adding previously simulated doses in an equivalent medium in terms of the atomic composition of the organ in question.
To perform the doses calculations we use Monte Carlo simulations. We simulated a cylindrical I-125 seed and compared our results against published data. Our proposal is to have the doses simulated previously in different arrangement of seed-absorbents, and then, considering the spacial positions of the seeds after the implants, these doses can be directly added, obtaining a very fast computation of the total dose. Two phantoms of prostates with permanent implant seeds in 2D and 3D arrangements were simulated.
The results of the proposed methodology were compared with two complete Monte Carlo simulations in 2D and 3D designs. Differences in doses were analysed, obtaining statistical discrepancies of less than 1% and reducing the simulation time by more than 4 orders of magnitude. With the proposed methodology, it is possible to perform rapid dose calculations in brachytherapy, using laptop or desktop computers.
The fundamental limitations of systemic therapeutic administration have prompted the development of local drug delivery platforms as a solution to increase effectiveness and reduce side effects. By confining therapeutics to the site of disease, local delivery technologies can enhance therapeutic index. This review highlights recent advances and opportunities in local drug delivery strategies for cancer treatment in addition to challenges that need to be addressed to facilitate clinical translation. The benefits of local cancer treatment combined with technological advancements and increased understanding of the tumor microenvironment, present a prime breakthrough opportunity for safer and more effective therapies.
Minimally invasive surgery has ushered in an era of popularized robotic-assistance for numerous urological procedures. There continues to be a great deal of interest in improving robotic technologies further. Concomitant robot-assisted laparoscopic radical prostatectomy and trans-rectal ultrasound has been employed to better visualize the neurovascular bundles and other adjacent critical structures during prostatectomy. There have also been attempts to improve prostate biopsy, brachytherapy and percutaneous renal interventions using robot-guidance. A magnetic resonance-safe robot has been designed and safely used to directly biopsy suspicious. Additionally, robot-guided brachytherapy seed placement for prostate cancer treatment has proven feasible and highly accurate. Lastly, robot-guidance for percutaneous renal access has been shown to be accurate and rapid. The evolution of robotic systems may facilitate the development of targeted therapies in urology. The growing emphasis on precision and reproducibility in medicine will likely put robotic technology at the forefront of future urological procedures.
Objective: Brachytherapy is one of several curative treatments for localized prostate cancer (PCa). The objective of this study was to report biochemical recurrence-free survival (BRFS), metastatic-free survival (MFS) and PCa-specific mortality after low-dose brachytherapy, stratified according to the D’Amico risk classification in a large Danish cohort.
Materials and methods: The study population comprised 502 men treated with brachytherapy in 1998–2012. BRFS was defined by the Phoenix criteria. Kaplan–Meier survival analysis was used to estimate BRFS and MFS. The cumulative PCa mortality was analysed using competing risk analyses. Multivariable Cox regression analysis was used to estimate risk of biochemical recurrence.
Results: In total, 206 men were classified with low-risk PCa, 265 men with intermediate-risk PCa and 33 men with high-risk PCa. Median follow-up was 6.6 years [95% confidence interval (CI) 6.2–7.0]. The 10 year BRFS was 90% (95% CI 83–97), 75% (95% CI 65–87) and 75% (95% CI 59–92) in men with low-, intermediate- and high-risk PCa, respectively. The 10 year MFS was 95% (95% CI 89–100), 93% (95% CI 88–98) and 78% (95% CI 57–99) in men with low-, intermediate- and high-risk PCa, respectively. The 10 year cumulative incidence of PCa mortality was 1% (95% CI 0–3), 5% (95% CI 0–12) and 11% (95% CI 0–25) for men with low-, intermediate- and high-risk PCa, respectively.
Conclusions: Low-dose brachytherapy offers good short- to intermediate-term cancer control in selected men with localized PCa. Further studies are needed for safety analyses and for comparison with other treatment modalities.
Statement of significance:
A new type of tissue marker for local administration to non-palpable breast tumors has been developed. The surgical guidance marker is based on derivatives of the biomaterial sucrose acetate isobutyrate and unlike currently used markers it is injectable in the tissue using thin needles, reducing the discomfort to the patients significantly. The marker confers CT contrast and has radioactive properties, meaning it also could find use in brachytherapy. The design of the iodine-125 labeled fiducial tissue marker enables control of dosimetry as well as a choice of iodine isotope used. The marker is anticipated to be clinical applicable due to its contrast performance in mice and its potential for enhanced flexibility in surgical procedures, compared to current methods.
Purpose:
To evaluate local recurrence in younger men treated with low-dose-rate (LDR) (125)I brachytherapy (BT) for localized prostate cancer.
Patients and methods:
A total of 192 patients (≤65-years-old) were treated with LDR (125)I-BT ± hormone therapy. Local failure was defined as any prostate-specific antigen (PSA) rise leading to salvage treatment or biochemical failure according to the Phoenix definition. A bounce was defined as a rise in the nadir of ≥0.2 ng/mL followed by spontaneous return. Proportions were compared using Fisher's exact tests; continuous variables using the unpaired t-test or its non-parametric equivalent. Cox proportional hazards models were applied for multivariable survival analysis.
Results:
Median follow-up was 66 months. The 5‑year local recurrence-free survival was 96.1%. Biopsy-proven local recurrence developed in 13 patients, 4 had a Phoenix-defined recurrence at the last follow-up. Androgen deprivation therapy was started in 1 patient without proven recurrence. Univariable risk factors for local recurrence were: at least 50% positive biopsies, intermediate risk, treatment with neoadjuvant hormone therapy, low preimplantation volume receiving 100% of the prescribed dose, and no bounce development. Hormone-naïve patients not attaining a PSA value <0.5 ng/mL during follow-up also had a higher risk of local recurrences. Cox regression demonstrated that the variables "at least 50% positive biopsies" and "bounce" significantly impacted local failure (hazard ratio, HR 1.02 and 11.59, respectively). A bounce developed in 70 patients (36%). Younger patients and those treated with a lower activity per volume had a higher chance of developing a bounce in the Cox model (HR 0.99 and 0.04, respectively).
Conclusion:
For younger men, LDR BT is a valid primary curative treatment option in low-risk and is to consider in intermediate-risk localized prostate cancer.
Accurate robotic targeting using magnetic resonance imaging (MRI) may serve as an important tool in permitting more accurate prostate cancer detection and focal treatments. Magnetic resonance-guided in-gantry biopsies are performed directly during MRI, eliminating issues with cross-modality image registration. Multiple studies indicate that magnetic resonance-guided biopsy is efficacious in the setting of previously failed transrectal ultrasound-guided biopsy. A challenge to utilizing this technology has been the development of magnetic resonance-safe robots. The PneuStep motor, a novel pneumatic step motor, and a robot-assisted targeting device have been developed to permit magnetic resonance-safe robot-guided biopsy that is largely free of human error, referred to as the MrBot. The MrBot has been utilized in a pilot study of transperineal direct MRI-guided biopsy in a population of men with elevated prostate-specific antigen, previous negative biopsy, and presence of a cancer suspicious region on MRI. No complications occurred, there were no unsuccessful biopsy attempts, and targeting was highly accurate. Magnetic resonance-guided robotic assistance has also been used to improve brachytherapy performance. The MrBot has been studied for this purpose in preclinical models, with promising results of accurate seed placement. Robot-assisted MR-guided targeting is promising technology that may aid in the diagnosis and treatment of prostate cancer.
The use of multiparametric magnetic resonance imaging (mp-MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request mp-MRI. Radiologists should be able to recognize the normal post-treatment MRI findings. Fibrosis and atrophic remnant seminal vesicles after prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, cryosurgery, and hormonal therapy tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images (T2WI) due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration either within or outside the gland. The authors provide a pictorial review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy, cryosurgery, and hormonal therapy.
Background:
Salvage therapeutic options for biochemical failure after primary radiation-based therapy include radical prostatectomy, cryoablation, high-intensity focused ultrasound (HIFU), brachytherapy (for post-EBRT patients) and androgen deprivation therapy (ADT). ADT and salvage prostate cryoablation (SPC) are two commonly considered treatment options for RRPC. However, there is an urgent need for high-quality clinical studies to support evidence-based decisions on treatment choice. Our study aims to determine the feasibility of randomising men with RRPC for treatment with ADT and SPC.
Methods:
The randomised controlled trial (CROP) was developed, which incorporated protocols to assess parameters relating to cryotherapy procedures and provide training workshops for optimising patient recruitment. Analysis of data from the recruitment phase and patient questionnaires was performed.
Results:
Over a period of 18 months, 39 patients were screened for eligibility. Overall 28 patients were offered entry into the trial, but only 7 agreed to randomisation. The majority reason for declining entry into the trial was an unwillingness to be randomised into the study. ‘Having the chance of getting cryotherapy' was the major reason for accepting the trial. Despite difficulty in retrieving cryotherapy temperature parameters from prior cases, 9 of 11 cryotherapy centres progressed through the Cryotherapists Qualification Process (CQP) and were approved for recruiting into the CROP study.
Conclusions:
Conveying equipoise between the two study arms for a salvage therapy was challenging. The use of delayed androgen therapy may have been seen as an inferior option. Future cohort studies into available salvage options (including prostate cryotherapy) for RRPC may be more acceptable to patients than randomisation within an RCT.
Although the optimal treatment for patients with high-risk prostate cancer remains unclear, combined radiotherapy and androgen-deprivation therapy (ADT) has become the standard of care; however, more recently, this paradigm has been challenged. In contemporary surgical series, using a multimodal approach with primary radical prostatectomy and adjuvant radiotherapy, when appropriate, had comparable efficacy in patients with high-risk disease to radiotherapy in combination with ADT. Furthermore, perioperative and postoperative morbidity associated with radical prostatectomy seem to be similar in patients with low-risk, intermediate-risk, or high-risk prostate cancer. Importantly, downstaging and downgrading of a substantial proportion of tumours after surgery suggests that many patients might be overtreated using radiotherapy and ADT. Indeed, the potential benefits of surgery include the ability to obtain tissues that can provide accurate histopathological information and, therefore, guide further disease management, in addition to local control of disease, a potentially reduced risk of developing metastases, and avoidance of long-term ADT. Thus, patients with high-risk disease should be offered a choice of first-line treatments, including surgery. However, effective management of high-risk prostate cancer is likely to require a multimodal approach, including surgery, radiotherapy, and neoadjuvant and adjuvant ADT, although the optimal protocols remain to be determined.
To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB).
The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS.
Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography-based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography-magnetic resonance image fusion is viewed as useful, but not mandatory.
Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians.
Dose escalation in order to improve the biochemical control in prostate cancer requires the application of irradiation techniques with high conformality. The dosimetric selectivity of three radiation modalities is compared: high-dose-rate brachytherapy (HDR-BT), intensity-modulated radiation radiotherapy (IMRT), and helical tomotherapy (HT).
Ten patients with prostate adenocarcinoma treated by a 10-Gy HDR-BT boost after external-beam radiotherapy were investigated. For each patient, HDR-BT, IMRT and HT theoretical treatment plans were realized using common contour sets. A 10-Gy dose was prescribed to the planning target volume (PTV). The PTVs and critical organs' dose-volume histograms obtained were compared using Student's t-test.
HDR-BT delivers spontaneously higher mean doses to the PTV with smaller cold spots compared to IMRT and HT. 33% of the rectal volume received a mean HDR-BT dose of 3.86 + or - 0.3 Gy in comparison with a mean IMRT dose of 6.57 + or - 0.68 Gy and a mean HT dose of 5.58 + or - 0.71 Gy (p < 0.0001). HDR-BT also enables to better spare the bladder. The hot spots inside the urethra are greater with HDR-BT. The volume of healthy tissue receiving 10% of the prescribed dose is reduced at least by a factor of 8 with HDR-BT (p < 0.0001).
HDR-BT offers better conformality in comparison with HT and IMRT and reduces the volume of healthy tissue receiving a low dose.
231 Background: Early biochemical detection and subsequent slow progression of recurrent prostate cancer after primary radiotherapy permit the delivery of potentially curative local salvage therapy (LST). Several LST options are available, including cryotherapy, brachytherapy (BT), and radical prostatectomy (RP). We studied the rates at which patients are offered, and receive LST after failure of primary radiotherapy. Methods: Patients with localized prostate cancer who received primary radiotherapy with curative intent between 1999-2000 were identified in the British Columbia radiotherapy database. Data on clinicopathologic features, primary therapy, PSA kinetics, and salvage therapy were collected retrospectively. We excluded patients with T4 tumors, PSA >40, or age >72 years at time of primary therapy. Biochemical recurrence (BCR) was defined by the Phoenix criteria. Patients were also deemed radiation failures if salvage therapy was started without meeting criteria for BCR. Results: Out of 1785 patien...
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Background: Active surveillance (AS) is considered appropriate for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, with grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may also be an initial option for men with favorable intermediate-risk PC. We estimated and compared the risk of PC-specific mortality (PCSM) following high dose radiation therapy and androgen deprivation therapy as appropriate amongst men with low, favorable intermediate, unfavorable intermediate, and high-risk PC. Methods: The study consisted of 6,595 consecutively treated men (median age: 68 years) with localized or locally advanced PC at the Chicago PC Center between 1997 and 2013. Fine and Gray competing risks regression analyses (table) were used to assess the risk of PCSM in men with favorable intermediate, unfavorable intermediate or high-risk compared to low-risk PC, adjusting for age at and year of treatment. Results: After median follow-up of 7.76 years, 820 men died: 72 of PC. While men with favorable intermediate-risk did not have significantly increased risk of PCSM as compared to low-risk PC (adjusted hazard ratio (HR) 1.28, 0.63-2.62 95% confidence interval (CI), p-value 0.49), men with high (adjusted HR 9.91, 5.48-17.94 95% CI, p-value <0.0001) or unfavorable intermediate-risk PC (adjusted HR 3.17, 1.60-6.30, p-value 0.001) did. Eight-year point estimates of PCSM were low: 0.68% [0.32-1.31% 95% CI] and 0.44% [0.25-0.75% 95% CI] for men with favorable intermediate and low-risk PC, respectively. Conclusions: Men with low and favorable intermediate-risk PC have similar and low estimates of PCSM during the first decade following standard management. These results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC. [Table: see text]
Purpose:
We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer.
Materials and methods:
Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months.
Results:
At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity.
Conclusions:
Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.
Purpose:
We reviewed the outcomes in men treated with permanent prostate brachytherapy (PPB).
Material and methods:
A total of 1,449 consecutive patients with a mean age of 68 years treated with PPB between 1992 and 2000 and mean pretreatment prostate specific antigen (PSA) 10.1 ng/ml were included in this study. Of the patients 55% presented with Gleason 6 tumors and 28% had Gleason 7 disease. A total of 400 patients (27%) were treated with neoadjuvant hormones and 301 (20%) were treated in combination with external radiation plus PPB. Several biochemical freedom from recurrence (BFR) definitions were determined. Statistical analysis consisted of log rank testing, Kaplan-Meier estimates and Cox regression analysis.
Results:
Median followup was 82 months with 39 patients at risk at for 144 months. Overall and disease specific survival at 12 years was 81% and 93%, respectively. The 12-year BFR was 81%, 78%, 74% and 77% according to the American Society for Therapeutic Radiology and Oncology (ASTRO), ASTRO-Kattan, ASTRO-Last Call and Houston definitions, respectively. The 12-year ASTRO-Kattan BFR using risk stratification was 89%, 78% and 63% in patients at low, intermediate and high risk, respectively (p = 0.0001). Multivariate analysis identified the dose that 90% of the target volume received (p <0.0001), pretreatment PSA (p = 0.001), Gleason score (p = 0.002), the percent positive core biopsies (p = 0.037), clinical stage (p = 0.689), the addition of hormones (p = 0.655) and the addition of external radiation (p = 0.724) for predicting BFR-ASTRO. Five-year disease specific survival was 44% in patients with a PSA doubling time of less than 12 months vs 88% in those with a PSA doubling time of 12 months or greater (p = 0.0001).
Conclusions:
PPB offers acceptable 12-year BFR in patients who present with clinically localized prostate cancer. Implant dosimetry continues as an important predictor for BFR, while the addition of adjuvant therapies such as hormones and external radiation are insignificant. In patients who experience biochemical failure it appears that PSA doubling time is an important predictor of survival.
Importance
Active surveillance (AS), per the National Comprehensive Cancer Network (NCCN) guidelines, is considered for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, given the grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may be appropriate for men presenting with favorable intermediate-risk PC.Objective
To estimate and compare the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM) following brachytherapy among men with low and favorable intermediate-risk PC.Design, Setting, and Participants
Prospective cohort study of 5580 consecutively treated men (median age, 68 years) with localized adenocarcinoma of the prostate treated with brachytherapy at the Prostate Cancer Foundation of Chicago between October 16, 1997, and May 28, 2013.Intervention
Standard of practice per the NCCN guidelines.Main Outcomes and Measures
Fine and Gray competing risks regression and Cox regression analyses were used to assess whether the risks of PCSM and ACM, respectively, were increased in men with favorable intermediate-risk vs low-risk PC. Analyses were adjusted for age at brachytherapy, year of treatment, and known PC prognostic factors.Results
After median follow-up of 7.69 years, 605 men had died (10.84% of total cohort), 34 of PC (5.62% of total deaths). Men with favorable intermediate-risk PC did not have significantly increased risk of PCSM and ACM compared with men with low-risk PC (adjusted hazard ratio [HR], 1.64; 95% CI, 0.76-3.53; P = .21 for PCSM; adjusted HR, 1.11; 95% CI, 0.88-1.39; P = .38 for ACM). Eight-year adjusted point estimates for PCSM were low: 0.48% (95% CI, 0.23%-0.93%) and 0.33% (95% CI, 0.19%-0.56%) for men with favorable intermediate-risk PC and low-risk PC, respectively. The respective estimates for ACM were 10.45% (95% CI, 8.91%-12.12%) and 8.68% (95% CI, 7.80%-9.61%).Conclusions and Relevance
Men with low-risk PC and favorable intermediate-risk PC have similarly low estimates of PCSM and ACM during the first decade following brachytherapy. While awaiting the results of ProtecT, the randomized trial of AS vs treatment, our results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC.
Objective
To analyze oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer (PCa) and to compare outcomes of patients within and outside the EAU guideline criteria (organ-confined PCa ≤ T2b, Gleason score ≤ 7 and preoperative PSA < 10 ng/mL) for SRP.Patients and MethodsA total of 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analyzed. Kaplan-Meier curves assessed time to biochemical recurrence (BCR), metastasis-free survival (MFS) and cancer specific survival (CSS). Cox regressions addressed factors influencing BCR and MFS. BCR was defined as PSA>0.2 ng/ml and rising, continence as the use of 0-1 safety pad per day and potency as an IIEF-5 score ≥18.ResultsMedian follow-up was 36 months. Following SRP 42.0% of the patients experienced BCR, 15.9% developed metastasis and 5.5% died from PCa. Patients fulfilling EAU guideline criteria were less likely to have positive lymph nodes and had significantly better BCR-free survival (5-year BCR-free survival 73.9% vs. 11.6% (p=0.001), respectively). In multivariate analysis, LDR-brachytherapy as primary treatment (p=0.03) and presence of positive lymph nodes at SRP (p=0.02) were significantly associated with worse BCR-free survival. The presence of positive lymph nodes or Gleason score > 7 at SRP were independently associated with metastasis. Urinary continence-rate 1 year after SRP was 74%. Seven patients (12.7%) experienced complications ≥III (Clavien grade).Conclusion
Salvage radical prostatectomy is a safe procedure providing good cancer control and reasonable urinary continence. Oncologic outcomes are significantly better in patients who met EAU guideline recommendations.This article is protected by copyright. All rights reserved.
Objectives
To analyse the impact of the uro-oncology multidisciplinary meeting (MDM) at an Australian tertiary centre on patient management decisions, and to develop criteria for patient inclusion in MDMs.Methods
Over a 3-month period, all cases presented at our weekly uro-oncology MDM were prospectively assessed, by asking the presenting clinician to state their provisional management plans and comparing this with the subsequent consensus decision. The impact of the MDM was graded as high if there was a major change in the management plan or if a plan was developed where there was none.ResultsOver the study period, 120 discussions about 107 patients were recorded. Prostate, urothelial, kidney and testis cancer represented 46 (38.3%), 36 (30%), 26 (21.6%) and 12 (10%) of the discussions, respectively. The MDM made high impact changes to the original plan in 32 (26.7%) cases. High impact changes were nearly twice as likely to occur in patients with metastatic disease as in those without metastases (P < 0.05). Primary cross referral between disciplines occurred in 40 (33.3%) cases, including 66.7% of testicular and 42% of bladder cancers but only 26% of prostate and 19% of kidney cancers (P < 0.02).Conclusions
The uro-oncology MDM alters management plans in about one-quarter of cases. Additionally, MDMs also serve other purposes, such as cross-referral or consideration for clinical trials. Patients should be discussed in MDMs if multimodal therapy may be required, clinical trial eligibility is being considered or if metastasis or recurrence is noted.
Objective
To investigate the results of performing laparoscopic radical prostatectomy (LRP) in patients with high-risk prostate cancer (HRPC): PSA ≥20 ng/ml +/- biopsy Gleason ≥8 +/- cT≥2c.Patients and methodsOf a total of 1,975 patients having LRP during a 159 month period from 2000-2013, 446 (22.6%) had HRPC; all patients were staged by pre-operative MRI or CT and isotope bone scanning.Median patient age (with range) = 64.0 (36-79) years; BMI = 27.0 (18-43) kg/m2; PSA = 8.1 (0.1-93) ng/ml and biopsy Gleason = 8 (6-10).All patients had a pelvic lymphadenectomy, which was done using an extended template after April 2008 (53.3%).Neurovascular bundle (NVB) preservation was done in 41.5% (bilateral = 26.3%; unilateral = 15.2%) of patients; an incremental or partial nerve-sparing technique was used in 99 of the 302 (32.8%) NVBs preserved.ResultsMedian gland weight = 58.5 (20-161) g; operating time = 180 (92-330) minutes; blood loss = 200 (10-1400) ml; post-op. hospital stay = 3.0 (2-7) nights; catheterization time = 14 (2-35) days; complication rate = 7.6%; node count = 16 (2-51); lymph node positivity = 16.2%; node involvement = 2 (1-8); margin positivity = 26.0%; up-grading = 2.5%; down-grading = 4.3%; up-staging from T1/2 to T3 = 24.7%; down-staging from T3 to T1/2 = 6.1%.No cases were converted to open surgery and 3 patients were transfused (0.7%) after surgery.At a mean follow-up of 24.9 (3-120) months 79.2% of patients were free of biochemical recurrence, 91.8% were continent and 64.4% of previously-potent non-diabetic men <70 years were potent after bilateral nerve preservation.Conclusion
The low morbidity, 55.4% specimen-confined rate, 26.0% positive surgical margin rate, 79.2% biochemical disease free survival, 91.8% continence rate and 64.4% potency rate at 35.2 months seen in this study serve as evidence firstly that surgery is an effective treatment for patients with HRPC, curing many and representing the first step of multi-modal treatment for others, and that LRP for HRPC appears to be as effective as open RP in this context.
Conventional clinical staging for prostate cancer has many limitations. This study evaluates the impact of adding MRI scans to conventional clinical staging for guiding decisions about radiotherapy target coverage.
This was a retrospective review of 115 patients who were treated between February 2002 and September 2005 with radical radiotherapy for prostate cancer. All patients had MRI scans approximately 2 weeks before the initiation of radiotherapy. The T stage was assessed by both conventional clinical methods (cT-staging) as well as by MRI (mT-staging). The radiotherapy target volumes were determined first based on cT-staging and then taking the additional mT staging into account. The number of times extracapsular extension or seminal vesicle invasion was incorporated into target volumes was quantified based on both cT-staging and the additional mT-staging.
Extracapsular extension was incorporated into target volumes significantly more often with the addition of mT-staging (46 patients (40%) ) compared with cT-staging alone (37 patients (32%) ) (P = 0.002). Seminal vesicle invasion was incorporated into target volumes significantly more often with the addition of mT-staging (21 patients (18%) ) compared with cT-staging alone (three patients (3%) ) (P < 0.001). A total of 23 patients (20%) had changes to their target coverage based on the mT-staging.
MRI scans can significantly change decisions about target coverage in radical radiotherapy for prostate cancer.
Objective
To evaluate the rates at which patients are offered and receive local salvage therapy (LST) after failure of primary radiotherapy for localized prostate cancer, as it is the only potentially curative treatment for localized recurrence but appears to be underutilized when compared with androgen-deprivation therapy (ADT) or observation.
Materials and methods
Patients with localized prostate cancer who received primary radiotherapy with curative intent between 1999 and 2000 were identified in the British Columbia Tumour Registry. Exclusion criteria included patient age >72 years, prostate-specific antigen>40 ng/ml, and clinical stage T4 at diagnosis. Data on clinicopathologic features, primary therapy, prostate-specific antigen kinetics, and salvage therapy were collected retrospectively. Radiation failure was defined as biochemical recurrence according to the Phoenix criteria or by initiation of salvage therapy.
Results
Of 1,782 patients treated in the study period, 1,067 met inclusion criteria. Of these, 257 failed radiation therapy. Radiation therapy failure was managed with observation (>12 mo) in 126 patients and ADT in 119. Of the observed patients, 66 subsequently received ADT. Five patients (1.8%) received LST (3 radical prostatectomy and 2 brachytherapy).
Conclusions
Only 2% of patients relapsing after radiation therapy for localized prostate cancer received LST. Although the benefits of LST are unproven, these findings reveal a possible underutilization of LST and indicate a need for enhanced collaboration between specialties to optimize care of this challenging cohort.
Background:
The diagnosis of prostate cancer has long been plagued by the absence of an imaging tool that reliably detects and localises significant tumours. Recent evidence suggests that multi-parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. This review serves as a background to a recent USANZ position statement. It aims to provide an overview of MRI techniques and to critically review the published literature on the clinical application of MRI in prostate cancer.
Technical aspects:
The combination of anatomical (T2-weighted) MRI with at least two of the three functional MRI parameters - which include diffusion-weighted imaging, dynamic contrast-enhanced imaging and spectroscopy - will detect greater than 90% of significant (moderate to high risk) tumours; however MRI is less reliable at detecting tumours that are small (<0.5 cc), low grade (Gleason score 6) or in the transitional zone. The higher anatomical resolution provided by 3-Tesla magnets and endorectal coils may improve the accuracy, particularly in primary tumour staging.
Screening:
The use of mpMRI to determine which men with an elevated PSA should undergo biopsy is currently the subject of two large clinical trials in Australia. MRI should be used with caution in this setting and then only in centres with established uro-radiological expertise and quality control mechanisms in place. There is sufficient evidence to justify using MRI to determine the need for repeat biopsy and to guide areas in which to focus repeat biopsy.
Image-directed biopsy:
MRI-directed biopsy is an exciting concept supported by promising early results, but none of the three proposed techniques have so far been proven superior to standard biopsy protocols. Further evidence of superior accuracy and core-efficiency over standard biopsy is required, before their costs and complexities in use can be justified.
Treatment selection and planning:
When used for primary-tumour staging (T-staging), MRI has limited sensitivity for T3 disease, but its specificity of greater than 95% may be useful in men with intermediate-high risk disease to identify those with advanced T3 disease not suitable for nerve sparing or for surgery at all. MRI appears to be of value in planning dosimetry in men undergoing radiotherapy, and in guiding selection for and monitoring on active surveillance.
The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high-dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30Gy in 3 fractions of HDR brachytherapy regimen. The D5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86Gy. The mean HDR fractionation equivalent dose, D98%, was 27.93 ± 0.84Gy. The V100% of the prostate target was 95.57% ± 3.47%. The V100% of the bladder and the rectum were 717.16 and 79.6mm(3), respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D98% to D80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D10% and D5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.
The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities.
Purpose:
We assess the risk of urinary incontinence after transurethral prostate resection in patients previously treated with prostate brachytherapy.
Materials and methods:
A total of 2,495 patients underwent brachytherapy with or without external beam radiation therapy for the diagnosis of prostate cancer between June 1990 and December 2009. Patients who underwent transurethral prostate resection before implantation were excluded from study. Overall 79 patients (3.3%) underwent channel transurethral resection of the prostate due to urinary retention or refractory obstructive urinary symptoms. Correlation analyses were performed using the chi-square (Pearson) test. Estimates for time to urinary incontinence were determined using the Kaplan-Meier method with comparisons using logistic regression and Cox proportional hazard rates.
Results:
Median followup after implantation was 7.2 years. Median time to first transurethral prostate resection after implantation was 14.8 months. Of the 79 patients who underwent transurethral prostate resection after implantation 20 (25.3%) had urinary incontinence compared with 3.1% of those who underwent implantation only (OR 10.4, 95% CI 6-18, p<0.001). Of the 15 patients who required more than 1 transurethral prostate resection, urinary incontinence developed in 8 (53%) compared with 19% of patients who underwent only 1 resection (OR 4.9, 95% CI 1.5-16, p=0.006). Exclusion of patients who underwent multiple transurethral prostate resections still demonstrated significant differences (18.8% vs 3.1%, OR 7.1, 95% CI 3.6-13.9, p<0.001). Median time from last transurethral prostate resection to urinary incontinence was 24 months. On linear regression analysis, hormone use and transurethral prostate resection after implantation were associated with urinary incontinence (p<0.05). There was no correlation between the timing of transurethral prostate resection after implantation and the risk of incontinence.
Conclusions:
Urinary incontinence developed in 25.3% of patients who underwent transurethral prostate resection after prostate brachytherapy. The risk of urinary incontinence correlates with the number of transurethral prostate resections. Patients should be counseled thoroughly before undergoing transurethral prostate resection after implantation.
Purpose:
To compare postoperative dosimetry and acute toxicity of new 0.5-mm (125)I seeds in 20-gauge (20G) diameter prostate brachytherapy (PB) needles with standard 0.8-mm seeds in 18G needles.
Methods and materials:
Postoperative dosimetry was performed on 100 consecutive PB patients treated with ThinSeeds in 20G needles and compared with 100 consecutively treated PB patients using standard-sized seeds and needles (18G). Dosimetry was performed on postoperative Day 1 CT scans. Acute urinary retention was also compared between these two groups. Acute toxicity was evaluated in 22 consecutively treated patients with thinner seeds/needles and compared with 22 consecutive concurrent patients treated with standard seeds and needles. All patients were evaluated by pre- and post-PB self-administered surveys, physical examinations on post-PB Day 1, and telephone surveys on Day 7. Endpoints included dysuria, acute urinary retention, hematuria, perineal pain/bruising, and International Prostate Symptom Score.
Results:
Post-PB dosimetric comparison demonstrated that the V100 (95% vs. 91%), D90 (161Gy vs.149Gy), V150 (55% vs. 45%), and RV100 (0.43cc vs. 0.30cc) were significantly (p<0.0004) higher in the 20G group. Urinary retention rates were 8% and 7% and median catheter-dependent durations were 7 and 14 days for the 20G and 18G groups, respectively. No significant differences were found for dysuria, hematuria, or International Prostate Symptom Score. Post-PB Day 1 perineal bruising and pain scores on Days 1 and 7 were significantly less (p<0.04) in 20G cohort.
Conclusions:
Smaller diameter needles and seeds resulted in improved post-PB Day 1 V100 and D90 dosimetry, and significantly less acute perineal pain and bruising.
Purpose:
To evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer.
Methods and materials:
One thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n=207), HDR with four fractions (n=252), or IMRT (n=869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42-44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival.
Results:
Overall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was 9,938; 17,514; and 4045 and 4962 and $4824 per 1% improvement in BC.
Conclusions:
In this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.
A well-established body of literature supports the use of high-dose-rate (HDR) brachytherapy as definitive treatment for localized prostate cancer. Most of the articles describe HDR as a boost with adjuvant external beam radiation, but there is a growing experience with HDR monotherapy.
The American Brachytherapy Society has convened a group of expert practitioners and physicists to develop guidelines for the use of HDR in the management of prostate cancer. This involved an extensive literature review and input from an expert panel.
Despite a wide variation in doses and fractionation reported, HDR brachytherapy provides biochemical control rates of 85-100%, 81-100%, and 43-93% for low-, intermediate-, and high-risk prostate cancers, respectively. Severe toxicity is rare, with most authors reporting less than 5% Grade 3 or higher toxicity. Careful attention to patient evaluation for appropriate patient selection, meticulous technique, treatment planning, and delivery are essential for successful treatment.
The clinical outcomes for HDR are excellent, with high rates of biochemical control, even for high-risk disease, with low morbidity. HDR monotherapy, both for primary treatment and salvage, are promising treatment modalities.
What's known on the subject? and What does the study add?
Very few comparative studies to date evaluate the results of treatment options for prostate cancer using the most sensitive measurement tools. PSA has been identified as the most sensitive tool for measuring treatment effectiveness. To date, comprehensive unbiased reviews of all the current literature are limited for prostate cancer.
This is the first large scale comprehensive review of the literature comparing risk stratified patients by treatment option and with long-term follow-up. The results of the studies are weighted, respecting the impact of larger studies on overall results. The study identified a lack of uniformity in reporting results amongst institutions and centres.
A large number of studies have been conducted on the primary therapy of prostate cancer but very few randomized controlled trials have been conducted. The comparison of outcomes from individual studies involving surgery (radical prostatectomy or robotic radical prostatectomy), external beam radiation (EBRT) (conformal, intensity modulated radiotherapy, protons), brachytherapy, cryotherapy or high intensity focused ultrasound remains problematic due to the non-uniformity of reporting results and the use of varied disease outcome endpoints. Technical advances in these treatments have also made long-term comparisons difficult. The Prostate Cancer Results Study Group was formed to evaluate the comparative effectiveness of prostate cancer treatments. This international group conducted a comprehensive literature review to identify all studies involving treatment of localized prostate cancer published during 2000–2010. Over 18 000 papers were identified and a further selection was made based on the following key criteria: minimum/median follow-up of 5 years; stratification into low-, intermediate- and high-risk groups; clinical and pathological staging; accepted standard definitions for prostate-specific antigen failure; minimum patient number of 100 in each risk group (50 for high-risk group). A statistical analysis (standard deviational ellipse) of the study outcomes suggested that, in terms of biochemical-free progression, brachytherapy provides superior outcome in patients with low-risk disease. For intermediate-risk disease, the combination of EBRT and brachytherapy appears equivalent to brachytherapy alone. For high-risk patients, combination therapies involving EBRT and brachytherapy plus or minus androgen deprivation therapy appear superior to more localized treatments such as seed implant alone, surgery alone or EBRT. It is anticipated that the study will assist physicians and patients in selecting treatment for men with newly diagnosed prostate cancer.
Purpose:
Prostate brachytherapy is an increasingly used treatment option for low- to intermediate-risk prostate cancer (PCa). However, patients with preexisting lower urinary tract symptoms (LUTS) and PCa, who would otherwise be good brachytherapy candidates, are often contraindicated because of the risk of postoperative urinary morbidity. We report our clinical experience with limited transurethral resection of the prostate (LTURP) and/or transurethral incision of the prostate (TUIP) months before brachytherapy to treat patients with LUTS and low- to intermediate-risk PCa.
Methods and materials:
Of 258 men undergoing prostate brachytherapy at our institution between 1998 and 2011, 42 were treated with planned LTURP and/or TUIP well before (mean, 5.7 months) seed implantation. Transurethral surgery was considered before brachytherapy for patients who at presentation required α-blocker therapy for LUTS, had an International Prostate Symptom Score greater than 14 off α-blockers, or had an elevated postvoid residual (>100 mL). Patients only proceeded to brachytherapy once LUTS resolved.
Results:
All 42 patients in our series underwent TUIP (25), LTURP (7), or TUIP/LTURP (10) with mean 5.7 months before prostate brachytherapy for low- or intermediate-risk PCa. Mean International Prostate Symptom Score, peak flow rate, and postvoid residual significantly improved after transurethral surgery, and improvement persisted at the latest followup. No patient developed retention, urethral necrosis, or urinary incontinence after transurethral surgery or brachytherapy (median followup, 39 months and range, 1-121).
Conclusions:
Planned LTURP and/or TUIP more than 4 months before brachytherapy is a safe and effective treatment strategy for men with LUTS and low- to intermediate-risk PCa.
To describe the acute and late rectal toxicity in 1006 prostate brachytherapy patients implanted 1998-2003. To determine whether rectal dose-volume histogram as well as patient and treatment factors were associated with rectal toxicity.
Median followup was 60.7 months. Rectal dosimetry was calculated as dose-volume histogram of the rectum using Day 28 CT-based dosimetry and expressed as volume of the rectum in cc receiving 50%, 100%, and 150% of the prescription dose (VR(50cc), VR(100cc), and VR(150cc), respectively). Univariate and multivariate analyses were performed to examine the influence of patient, implant, dosimetry, and learning curve factors on the development of acute and late toxicities using a modified Radiation Therapy Oncology Group (RTOG) scale. Acute toxicity was analyzed using logistic regression and late toxicity using Cox proportional hazards regression. Analysis of variance was used to examine the association between rectal toxicity and rectal dose.
Rectal dosimetry in 93.5% and rectal toxicity in 96.2% have been recorded. Median VR(100)=1.05cc. Late RTOG Grades 0, 1, 2, 3, and 4 were recorded in 68%, 23%, 7.3%, 0.9%, and 0.2% patients, respectively. On multivariate analysis, acute RTOG ≥2 rectal toxicity was associated with urinary retention (p=0.036) and learning curve (p=0.015); late RTOG ≥2 was associated with the presence of acute toxicity (p=0.0074), higher VR(100) (p=0.030) and learning curve (p=0.027).
Late rectal RTOG ≥2 rectal toxicity in this cohort was 8%. Increased VR(100), presence of acute rectal toxicity, and learning curve were associated with higher rate of late RTOG ≥2 toxicity. Severe late rectal toxicity after prostate brachytherapy was rare.
High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients.
There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.
The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%.
High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.
To evaluate the 10-year outcomes of intermediate- and high-risk prostate cancer patients treated with a prospective dose escalation hypofractionated trial of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR) brachytherapy boost.
From 1992 to 2007, 472 patients were treated with a HDR boost at William Beaumont Hospital. They had at least one of the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason score of ≥7, or clinical stage ≥T2b. Patients received 46-Gy P-EBRT and an HDR boost. The HDR dose fractionation was divided into two dose levels. The prostate biologically equivalent dose (BED) low-dose-level group received <268 Gy, and the high-dose group received >268 Gy . Phoenix biochemical failure (BF) definition was used.
Median follow-up was 8.2 years (range, 0.4-17 years). The 10-year biochemical failure rate of 43.1% vs. 18.9%, (p < 0.001), the clinical failure rate of 23.4% vs. 7.7%, (p < 0.001), and the distant metastasis of 12.4% vs. 5.7%, (p = 0.028) were all significantly better for the high-dose level group. On Cox multivariate analysis, higher BED levels (p = 0.017; hazard ratio [HR] = 0.586), pretreatment PSA assays (p < 0.001, HR = 1.022), and Gleason scores (p = 0.004) were significant variables for reduced biochemical failure. Higher dose levels (p, 0.002; HR, 0.397) and Gleason scores (p < 0.001) were significant for clinical failure. Grade 3 genitourinary complications were 2% and 3%, respectively, and grade 3 gastrointestinal complication was <0.5%.
This prospective trial using P-EBRT with HDR boost and hypofractionated dose escalation demonstrates a strong dose-response relationship for intermediate- and high-risk prostate cancer patients. The improvement at 10 years for locoregional control with higher radiation doses (BED, > 268 Gy) has significantly decreased biochemical and clinical failures as well as distant metastasis.
To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I(125) brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience.
Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I(125) monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots.
Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups.
I(125) monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.
To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change.
Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months.
By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose.
EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.
We report on a retrospective comparison of biochemical outcomes using an ultra-high dose of conventionally fractionated intensity-modulated radiation therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR) brachytherapy to increase the biologically effective dose of IMRT.
Patients received IMRT of 86.4Gy (n=470) or HDR brachytherapy (21Gy in three fractions) followed by IMRT of 50.4Gy (n=160). Prostate-specific antigen (PSA) relapse was defined as PSA nadir+2. Median followup was 53 months for IMRT alone and 47 months for HDR.
The 5-year actuarial PSA relapse-free survival (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%, and 93% vs. 71%, for National Comprehensive Cancer Network low- (p=0.71), intermediate- (p<0.001), and high-risk (p=0.23) groups, respectively. Treatment (p=0.0006), T stage (p<0.0001), Gleason score (p<0.0001), pretreatment PSA (p=0.0037), risk group (p<0.0001), and lack of androgen-deprivation therapy (p=0.0005) were significantly associated with improved PRFS on univariate analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p=0.0012, hazard ratio [HR]=0.184); age (p=0.0222, HR=0.965); and risk group (p<0.0001, HR=2.683) were associated with improved PRFS on multivariate analysis.
Dose escalation of IMRT by adding HDR brachytherapy provided improved PRFS in the treatment of prostate cancer compared with ultra-high-dose IMRT, independent of risk group on multivariate analysis, with the most significant benefit for intermediate-risk patients.
To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer.
Between September 2008 and March 2009, we transperitoneally injected 9 mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18 mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200 cGy followed by intensity-modulated radiation therapy to 5,040 cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme.
Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 +/- 3mm (mean +/- SD) and 10 +/- 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 +/- 13 cGy with Hylaform vs. 106 +/- 20 cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04).
By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.
Health-related quality of life (HRQOL) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available. The aim of the present study was to prospectively assess long-term HRQOL 6 years after (125)I prostate brachytherapy.
A total of 127 patients treated with (125)I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL questionnaire at five time-points: before treatment and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTCQLQ-C30), and the tumor-specific EORTC prostate cancer module (EORTC-PR25). A change in a score of >/=10 points was considered clinically relevant.
Overall, the HRQOL at 6 years after (125)I prostate brachytherapy did not significantly differ from baseline. Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms, bowel symptoms, pain, physical functioning, and sexual activity (p <.01), most changes were not clinically relevant. A statistically significant improvement at 6 years was seen for mental health, emotional functioning, and insomnia (p <.01). The only clinically relevant changes were seen for emotional functioning and sexual activity.
This is the first study presenting prospective HRQOL data up to 6 years after (125)I prostate brachytherapy. HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment. (125)I prostate brachytherapy did not adversely affect patients' long-term HRQOL.
A course of one to three large fractions of high dose rate (HDR) interstitial brachytherapy is an attractive alternative to intensity modulated radiation therapy (IMRT) for delivering boost doses to the prostate in combination with additional external beam irradiation for intermediate risk disease. The purpose of this work is to quantitatively compare single-fraction HDR boosts to biologically equivalent fractionated IMRT boosts, assuming idealized image guided delivery (igIMRT) and conventional delivery (cIMRT). For nine prostate patients, both seven-field IMRT and HDR boosts were planned. The linear-quadratic model was used to compute biologically equivalent dose prescriptions. The cIMRT plan was evaluated as a static plan and with simulated random and setup errors. The authors conclude that HDR delivery produces a therapeutic ratio which is significantly better than the conventional IMRT and comparable to or better than the igIMRT delivery. For the HDR, the rectal gBEUD analysis is strongly influenced by high dose DVH tails. A saturation BED, beyond which no further injury can occur, must be assumed. Modeling of organ motion uncertainties yields mean outcomes similar to static plan outcomes.
Published clinical information on the safety and efficacy of (131)Cs implants is limited. We provide consensus recommendations for (131)Cs prostate brachytherapy based on experience to date.
The Cesium Advisory Group (CAG) consists of experienced (131)Cs users. Recommendations are based on three clinical trials, one of which has completed accrual and has been published in the peer reviewed literature, and combined CAG experience of more than 1200 (131)Cs implants.
We recommend using 1.059cGyh(-1)U(-1) as the dose rate constant for the IsoRay source. The prescription for monotherapy implants is 115Gy and when combined with 45-50Gy external beam it is 85Gy. Suggested individual source strength ranges from 1.6 to 2.2U. The release criterion for (131)Cs implants is 6mRh(-1) at 1m. (131)Cs brachytherapy should be performed differently from (125)I and (103)Pd brachytherapy: source placement is further from the urethra and rectum; the prostate V(150) should be < or =45%; sufficient margins may be obtained while limiting source placement to the capsule or close to the capsule. The increased dose rate may cause degradation of postimplant quantifiers due to edema. However, large variability in the magnitude and rate of resolution of edema make determination of the most representative postoperative imaging time impossible. The CAG recommends postimplant imaging on the day of the implant. Recommended postimplant evaluation goals include prostate D(90) greater than the prescription dose; maintaining D(u)(,30)<140% of the prescription dose and keeping V(r)(,100)<0.5cm(3).
It was the consensus of the CAG that optimal (131)Cs implants should be performed differently from those performed with (125)I or (103)Pd. Guidelines have been established to allow for safe and effective delivery of (131)Cs prostate brachytherapy.
A computerized planning procedure has been developed for CT-guided transperineal prostate implants. The segment for custom planning of perineal needle orientations allows placement of I-125 seeds in the entire prostate gland while avoiding the pubic bones. Least-squares optimization (LSO) is used to obtain the seed-loading pattern along the needles. The optimized seed distribution produces a better fit between treatment and target volumes than that obtained from our previous manual technique. Also, the present semi-automatic technique reduces planning time by about a factor of 10 compared to that of the manual approach.
To review post implant morbidity in patients with prior transurethral prostate resection (TURP).
Nineteen patients with stage T1-T2 prostatic carcinoma and prior TURP were treated with I-125 or Pd-103 implantation from 1991 through 1994. Follow-up ranged from 1 to 6 years (median: 3 years). The time from TURP to implantation ranged from 2 months to 15 years (median: 3 years).
Only one patient developed mild urinary stress incontinence, 6 months following his I-125 implant. The actuarial freedom from permanent urinary incontinence at 3 years after implantation was 94%. No patient required urethral dilatation for urethral stricture. Eleven patients were sexually potent prior to implantation. At 3 years after treatment, all patients had maintained potency.
In our experience, there has been remarkably little adverse sequelae following I-125 or Pd-103 implantation in patients with a prior history of TURP.
Our aim was to define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer.
In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%.
Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH. Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry. Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably.
These data provide a picture of current practice regarding the management of BPH and prostate cancer.
Urinary retention is a frequently reported complication following radioactive seed implantation of the prostate. If retention is refractory, a post-implant transurethral prostatic resection may ultimately be required to relieve obstruction, leading to an increased risk of urinary incontinence. In this series the incidence of prolonged urinary retention was determined, and the effect of pretreatment and treatment related factors was analyzed to identify high risk patients.
A total of 251 patients with organ confined prostate carcinoma underwent transperineal prostate seed implantation. Of the patients 114 were implanted with 103palladium (103Pd) and 137 with 125iodine seeds. Of the patients who were implanted with 103Pd 90 received 3 months of neoadjuvant hormonal therapy. All patients had International Prostate Symptom Scores (I-PSS) recorded before implantation to assess the degree of urinary symptoms. In the patients receiving neoadjuvant hormones prostate volumes and I-PSS were recorded before initiation of hormone treatment and 3 months later at the time of implant.
Urinary retention developed in 14 patients requiring catheterization for more than 48 hours. Median time to onset was 1 day after implant. Of these patients 6 ultimately required transurethral prostatic resection to relieve urinary obstruction. No patient had urinary incontinence following implantation or transurethral prostatic resection. Multivariate analysis revealed that pretreatment I-PSS, and combined treatment with hormonal therapy and 103Pd predicted for the development of retention. Patients with I-PSS 20 or greater had a 29% risk, I-PSS 10 to 19, 11% risk and I-PSS less than 10, 2% risk of retention. Neither patient age, clinical stage, prostate specific antigen, Gleason score, use of 125I nor prostate volume was significant. A subgroup analysis of patients receiving hormonal therapy and 103Pd revealed that those with persistent urinary symptoms (I-PSS 10 or greater) following 3 months of hormonal therapy had the greatest risk of prolonged retention (37%).
The overall risk of prolonged urinary retention following prostate implantation was low in our series. Using the I-PSS questionnaire, high risk patients can be identified before treatment. Patients with significant pretreatment urinary symptoms or persistent urinary symptoms following 3 months of hormonal therapy and then implantation with 103Pd have the greatest risk.
Ultrasound-guided interstitial implantation of radioactive seeds is a common treatment for early stage prostate cancer. One of the risks associated with this therapy is seed embolization to the lung. This paper reports on the incidence and possible adverse effects of seed migration.
Two hundred ninety consecutive patients were treated with permanent radioactive seed brachytherapy for prostate cancer between January 1 and December 31, 1995. One hundred fifty-four patients were treated with iodine-125 (I-125), and 136 patients were treated with palladium-103 (Pd-103). All but one patient had a routine post implant chest radiograph (CXR), leaving 289 evaluable patients.
Twenty radioactive seed pulmonary emboli were identified in 17 patients; 3 patients had two emboli each. The radioactive seed pulmonary embolism rate for the entire group of patients was 5.9%. Acute pulmonary symptoms were not reported by any patient in this series. One hundred forty-six study patients were implanted with free seeds alone (136 Pd-103 and 11 I-125), and 143 were implanted with linked seed embedded in a vicryl suture for the peripheral portions of their implants. The radioactive seed embolization rate by patient was 11% (16/146) versus 0.7% (1/143) for free seed implants and implants utilizing linked seeds, respectively. The difference was statistically significant, p = 0.0002. No patient had detectable morbidity as a consequence of seed emboli.
The use of linked seeds embedded in vicryl sutures for the peripheral portion of permanent radioactive seed prostate implants significantly reduced the incidence of pulmonary seed embolization in patients treated with the Seattle technique.
To determine the clinical utility of the percentage of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for men with PSA-detected or clinically palpable prostate cancer.
A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men while accounting for the previously established risk groups that are defined according to pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage. The findings were then tested using an independent surgical database that included data for 823 men.
Controlling for the known prognostic factors, the percentage of positive prostate biopsies added clinically significant information (P <.0001) regarding time to PSA failure after RP. Specifically, 80% of the patients in the intermediate-risk group (1992 AJCC T2b, or biopsy Gleason 7 or PSA > 10 ng/mL and </= 20 ng/mL) could be classified into either an 11% or 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated in the intermediate-risk patients using an independent surgical data set.
The validated stratification of PSA outcome after RP using the percentage of positive prostate biopsies in intermediate-risk patients is clinically significant. This information can be used to identify men with newly diagnosed and clinically localized prostate cancer who are at high risk for early (</= 2 years) PSA failure and, therefore, may benefit from the use of adjuvant therapy.
Patients with localized prostate cancer who had a prior open prostatectomy or transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) may be at risk for greater morbidity when treated with brachytherapy. This analysis examines the morbidity following brachytherapy using the real-time method to determine if patients with a history of TURP are at increase risk for developing complications.
An ultrasound-guided transperineal interactive prostate seed was implanted in 419 patients with T1-T2 prostate cancer. All patients were implanted using a peripheral weighting of sources (75%) with the interior sources placed at least 5 mm from the urethra. The patients were divided into two groups: group 1 consisted of 376 patients (89.7%) without a prior TURP, and group 2 consisted of 43 patients (10.3%) who had a TURP prior to their implant. The mean age, prostate-specific antigen level, Gleason score, clinical stage, prostate volume, isotope implanted, and number of patients treated with neoadjuvant hormone therapy were comparable for both groups.
Median follow-up for group 1 was 12 months and for group 2 was 18 months. No patients suffered from radiation-related proctitis or cystitis in either group of patients. Two patients in group 2 implanted with iodine 125 and who had a history of two prior TURPs developed mild superficial urethral necrosis (SUN). The actuarial freedom from developing superficial urethral necrosis at 4 years was 84% in patients with a history of prior TURP. There were no episodes of SUN in group 1 and no cases of incontinence reported in either group of patients. The actuarial rate of potency was 78% at 2 years.
Whereas other techniques of seed implantation report incontinence in patients who had a prior open prostatectomy or TURP, the real-time method combined with peripheral loading avoids this complication.
The clinical utility of the percentage of positive prostate biopsies in predicting prostate specific antigen (PSA) outcome after radical prostatectomy (RP) or external-beam radiation therapy (EBRT) for men with PSA-detected or palpable prostate cancer is not established.
A Cox regression multivariable analysis was used to determine whether percent-positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men, while accounting for the previously established risk groups based on the pretreatment PSA concentration biopsy Gleason score, and the 1992 American Joint Commission on Cancer clinical T stage.
In the intermediate-risk group, 80% of the patients (stage T(2b) or biopsy Gleason 7 or PSA 10-20 ng/mL) could be classified into either an 11% or an 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated using an independent surgical (N = 823) and radiation (N = 473) data set. Percent-positive prostate biopsies added clinically significant information regarding time to PSA failure after RP.
The percentage of positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome after RP or EBRT.