Treatment Of Early Stage Prostate Cancer Research Articles

Comparison of Volumetric Modulated Arc Therapy and Fixed Field Intensity Modulated Radiotherapy for Radical Treatment of Early Prostate Cancer using Hypofractionated Radiotherapy

Objective: To investigate the dosimetric advantages of volumetric modulated arc therapy over intensity-modulated radiation therapy for radical treatment of early-stage prostate cancer.
 Study Design: Retrospective longitudinal study.
 Place and Duration of Study: Department of Radiation Oncology, Combined Military Hospital, Rawalpindi Pakistan, from Jan to Jun 2019.
 Methodology: Two treatment plans; one volumetric modulated arc therapy and other intensity-modulated radiation therapy, were made for 13 patients undergoing radical radiotherapy for early prostate cancer. Conformity index, Homogeneity index, the volume of rectum and bladder receiving a dose of 50 Gy or more, monitor units employed and treatment delivery time were compared between both techniques.
 Results: Volumetric modulated arc therapy plans showed statistically better conformity index and Homogeneity index with significantly lower doses to the rectum and bladder than intensity-modulated radiation therapy plans. The number of monitor units (MUs) employed and treatment delivery time were also reduced significantly with volumetric modulated arc therapy.
 Conclusion: Volumetric modulated arc therapy generates dose-metrically better radiotherapy plans than intensity-modulated radiation therapy and can deliver the required dose faster.Keywords: Hypofractionated radiotherapy, Intensity-modulated radiation therapy, Prostate cancer, Volumetric modulated arc therapy.

Optimisation and validation of a co-manipulated robot for brachytherapy procedure.

Low-dose rate brachytherapy is the referent treatment for early-stage prostate cancer and consists in manually inserting radioactive seeds within the organ to destroy tumorous cells. This treatment is inaccurate leading to side effects. Researchers developed robots to improve this technique. Despite ameliorating accuracy, they cannot be clinically used because of size and acceptability. Therefore, a 6-DOFparallel and co-manipulated robot is proposed to meet these requirements. To fulfil the application requirements, a compact design was modelled. The robot's optimal dimensions were defined by establishing kinematics and implementing genetic algorithm. The robot's relevance was evaluated by measuring workspace and needle placement errors. The robot fits into a cube of 300×300×300mm3 and provides a free-singularity workspace of 55×55×150mm3 with a possible end-effector rotation of 15° and a needle placement error <3mm. The results are promising and prove that our robot fulfils the application requirements and presents a beneficial alternative to the manual procedure.

The Role of Emotion in Cancer Surgery Decisions: Applying Concepts From Decision Psychology.

The Role of Emotion in Cancer Surgery Decisions: Applying Concepts From Decision Psychology.

Stereotactic body radiotherapy (SBRT) versus conventional fractionated intensity-modulated radiotherapy (CF-IMRT) for patients with early-stage localized prostate cancer: One-year late toxicity results from a prospective randomized phase II study.

27 Background: It remains uncertain whether stereotactic body radiotherapy (SBRT) is superior to conventional fractionated intensity-modulated radiotherapy (CF-IMRT) in the treatment of early-stage prostate cancer. Here we report the 1-year late toxicity results from this randomized phase II study comparing SBRT and CF-IMRT. Methods: The primary endpoint of this single centre randomized phase II study is the health-related quality of life (HRQOL), as measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) instrument. The secondary endpoints include toxicities, biochemical control and overall survival. We enrolled low and intermediate risk localized prostate cancer patients (T1-T2, Gleason score ≤7 and PSA &lt;20). Patients were randomly assigned in a 1:1 ratio to receive either CF-IMRT with 38 fractions of 2 Gy in 7.5 weeks (five fractions per week) or SBRT with 5 fractions of 7.25 Gy in 2 weeks (three fractions per week). Neoadjuvant androgen-deprivation treatment is optional for the intermediate risk patients. A 1-year late adverse event is defined as the first occurrence of worst severity of the adverse event within 1 year after the completion of RT, and it was evaluated with the Common Terminology Criteria for Adverse Events (version 4.0). Patient recruitment was completed in May 2017. Results: Between Jan 2015 and May 2017, 68 patients were recruited and 4 patients were not eligible. 64 patients were randomized to treatments with SBRT (n=31) or CF-IMRT (n=33). At 1- year follow-up, two grade 3 genitourinary (GU) late toxicities, one in each arm (3%), were reported. SBRT patients experienced significantly less ≥ grade 1 late gastrointestinal (GI) toxicities (SBRT vs IMRT: 64% vs 84%, p=0.041) and similar ≥grade 1 late GU toxicities (SBRT vs IMRT: 93% vs 100%, p=0.2307) to IMRT patients. Conclusions: SBRT results in significantly less 1-year late GI toxicities than CF-IMRT in with low and intermediate risk prostate cancer. The study is registered at ClinicalTrials.gov (NCT02339701). Clinical trial information: NCT02339701.

The role of immune checkpoint inhibitors inprostate cancer.

Prostate cancer (PC) is the most commonly diagnosed malignant tumour and the third cause of cancer deaths among men in Europe. The treatment of early-stage PC is very effective and in many cases allows achievement of a complete cure, whereas the treatment of metastatic prostate cancer (mPC) is still a huge challenge for clinicians. New therapeutic strategies for mPC are urgently needded. One of the most promising methods of treatment is anticancer immunotherapy including the monoclonal antibodies against immune checkpoint inhibitors. To present the potential possibilities of using checkpoint inhibitors blockage in the treatment of mPC, and to overview the results of recent research on immune checkpoint inhibitors in patients with PC. Recent studies suggest that monoclonal antibodies directed against immune checkpoint inhibitors in combination with traditional therapy may become a breakthrough in the treatment of mPC in the near future. The immunotherapy using monoclonal antibodies against immune checkpoint inhibitors seems to be a new opportunity for patients with advanced PC. The key to achieve the maximum anti-tumour response is to choose the best candidates for this therapy and determine the optimal sequence and combination of drugs. The introduction of immunotherapy as the standard treatment of patients with advanced PC requires further studies.

Testicular vs adrenal sources of hydroxy-androgens in prostate cancer

Neoadjuvant androgen deprivation therapy (NADT) is one strategy for the treatment of early-stage prostate cancer; however, the long-term outcomes of NADT with radical prostatectomy including biochemical failure-free survival are not promising. One proposed mechanism is incomplete androgen ablation. In this study, we aimed to evaluate the efficiency of serum hydroxy-androgen suppression in patients with localized high-risk prostate cancer under NADT (leuprolide acetate plus abiraterone acetate and prednisone) and interrogate the primary sources of circulating hydroxy-androgens using our recently described stable isotope dilution liquid chromatography mass spectrometric method. For the first time, three androgen diols including 5-androstene-3β,17β-diol (5-adiol), 5α-androstane-3α,17β-diol (3α-adiol), 5α-androstane-3β,17β-diol (3β-adiol), the glucuronide or sulfate conjugate of 5-adiol and 3α-adiol were measured and observed to be dramatically reduced after NADT. By comparing patients that took leuprolide acetate alone vs leuprolide acetate plus abiraterone acetate and prednisone, we were able to distinguish the primary sources of these androgens and their conjugates as being of either testicular or adrenal in origin. We find that testosterone, 5α-dihydrotestosterone (DHT), 3α-adiol and 3β-adiol were predominately of testicular origin. By contrast, dehydroepiandrosterone (DHEA), epi-androsterone (epi-AST) and their conjugates, 5-adiol sulfate and glucuronide were predominately of adrenal origin. Our findings also show that NADT failed to completely suppress DHEA-sulfate levels and that two unappreciated sources of intratumoral androgens that were not suppressed by leuprolide acetate alone were 5-adiol-sulfate and epi-AST-sulfate of adrenal origin.

Retrospective Review of Outcomes With Active Surveillance and Active Treatment for Early-Stage Prostate Cancer in a Contemporary Series

Retrospective Review of Outcomes With Active Surveillance and Active Treatment for Early-Stage Prostate Cancer in a Contemporary Series

A comparison of the acute toxicities using moderate hypo-fractionated intensity-modulated radiation therapy or volumetric modulated arc therapy for the treatment of early-stage prostate cancer

AbstractAimThis study compared the acute toxicities reported during radiotherapy treatment using either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) to deliver a moderate hypo-fractionated treatment for early-stage prostate cancer.Material and methodsAcute toxicities are routinely reported at the clinical site for all patients using the Common Terminology Criteria for Adverse Events. Toxicity assessment is performed on day 1 of treatment, then once weekly thereafter. The recorded toxicities of 40 cases treated with five-field IMRT, and 32 cases treated using VMAT were retrospectively compared. All cases were prescribed 73·68 Gy in 28 fractions. Eight symptoms were assessed; diarrhoea, proctitis, fatigue, pain, dermatitis, urinary frequency, urinary retention and urinary tract pain.ResultsIn terms of the overall toxicity recorded, VMAT was shown to reduce the toxicities of dermatitis, fatigue, pain and urinary frequency (p&amp;lt;0·05). Using IMRT, grade 2 toxicities were reported for proctitis, pain, urinary frequency, urinary retention and urinary tract pain. Using VMAT, grade 2 toxicities were reported for urinary frequency and urinary retention.FindingsThe research reported here is one of the first publications to demonstrate that VMAT is associated with decreased toxicities compared with IMRT for the treatment of early-stage prostate cancer.

Costs in different states of prostate cancer

Objectives. This cross-sectional study assesses resource use and costs in different states of prostate cancer (PCa) in a real-life setting. Costs were estimated as incremental costs due to cancer for a six-month period and they included direct medical costs, productivity costs and costs of informal care.Methods. Resource use and cost data, irrespective of who the payer was, were retrieved from the registries for 611 PCa patients in the Helsinki area in Finland. In addition, patients answered background questions concerning informal care, work capacity and educational status. Patients were divided into four mutually exclusive groups based on disease state and time from diagnosis: primary (local disease, first six months after diagnosis; n = 47), rehabilitation (local disease, 0.5–1.5 years after diagnosis or recurrence; n = 158), remission (local disease, more than 1.5 years after diagnosis; n = 317) and metastatic (after detection of metastases; n = 89).Results. Costs differed markedly between the states of disease. Mean direct health care costs for the six-month periods were: primary treatment state €2750, rehabilitation state €1143, remission state €760 and metastatic state €7423. Productivity costs were also highest (€4277) in the metastatic state. Overall, the average share of indirect costs was around one third of the total costs. However, when including informal care, their combined share of the total costs increased to around half or more.Conclusions. The results provided state-specific estimates of the direct health care and indirect costs of PCa in Finland. The treatment of metastatic disease is significantly more costly than treatment of early stage PCa. Although direct medical costs were higher compared to productivity costs, they should be taken into consideration when evaluating the costs of PCa.

MP32-18 A COMPARISON BETWEEN UROLOGY AND OTHER SPECIALITIES IN THE UTILIZATION OF TWITTER AT INTERNATIONAL CONFERENCES

diagnostic prostate-biopsy, as well as treatment for early-stage prostate-cancer, in Israel. METHODS: This is a population-based cohort study, using Clalit electronic-databases. Clalit is the largest HMO in Israel and insures over 4,000,000 subjects. Our cohort included all 220,861 Clalit male patients who were 75 or older in January 1st 2009. We recorded all PSA tests, diagnostic biopsies, and treatments for early-stage prostate-cancer, between the years 2009-2013. We performed a uni and multivariable analyses to determine patient and doctor related variables that were associated with PSA testing among elderly patients. RESULTS: Excluding patients who had a prior prostate-cancer diagnosis our final cohort included 213,814 subjects. During the study period, 187,228 PSA tests were performed on 55,886 subjects (26.1%). The median PSA was 2.15 ng/ml (IQR 0.92, 4.7). PSA tests were common even among subjects older than 85, with 10,594 of 79,731 subjects tested (13.3%). Prostate biopsies were performed on 1913 subjects. Of those, 818 were then diagnosed with prostate-cancer. One month following prostate biopsies we found 103 associated emergency department visits and even 4 deaths. On Multivariable analysis age, marital status and type of health insurance were independent predictors of PSA testing. Surprisingly, Charleston comorbidity was also an independent predictor (a higher Charleston score was associated with an increased risk of PSA testing). The vast majority of PSA tests were performed by family physicians (76%). The number of years of practice was the only Doctor associated predictors of PSA testing. Performing other screening tests was not associated with PSA testing. CONCLUSIONS: We have demonstrate a large overuse of PSA testing among elderly in Israel, even among those older than 85. As appose to PSA testing, which may be considered harmless, biopsies are defiantly not. Our study demonstrates that biopsies are also commonly performed and rarely may cause severe consequences. We are amongst the first studies to test doctor associated predictors. Future interventional studies are required to try and mitigate this phenomenon.

Transfected Poly(I:C) Activates Different dsRNA Receptors, Leading to Apoptosis or Immunoadjuvant Response in Androgen-independent Prostate Cancer Cells

Despite the effectiveness of surgery or radiation therapy for the treatment of early-stage prostate cancer (PCa), there is currently no effective strategy for late-stage disease. New therapeutic targets are emerging; in particular, dsRNA receptors Toll-like receptor 3 (TLR3) and cytosolic helicases expressed by cancer cells, once activated, exert a pro-apoptotic effect in different tumors. We previously demonstrated that the synthetic analog of dsRNA poly(I:C) induces apoptosis in the androgen-dependent PCa cell line LNCaP in a TLR3-dependent fashion, whereas only a weak apoptotic effect is observed in the more aggressive and androgen-independent PCa cells PC3 and DU145. In this paper, we characterize the receptors and the signaling pathways involved in the remarkable apoptosis induced by poly(I:C) transfected by Lipofectamine (in-poly(I:C)) compared with the 12-fold higher free poly(I:C) concentration in PC3 and DU145 cells. By using genetic inhibition of different poly(I:C) receptors, we demonstrate the crucial role of TLR3 and Src in in-poly(I:C)-induced apoptosis. Therefore, we show that the increased in-poly(I:C) apoptotic efficacy is due to a higher binding of endosomal TLR3. On the other hand, we show that in-poly(I:C) binding to cytosolic receptors MDA5 and RIG-I triggers IRF3-mediated signaling, leading uniquely to the up-regulation of IFN-β, which likely in turn induces increased TLR3, MDA5, and RIG-I proteins. In summary, in-poly(I:C) activates two distinct antitumor pathways in PC3 and DU145 cells: one mediated by the TLR3/Src/STAT1 axis, leading to apoptosis, and the other one mediated by MDA5/RIG-I/IRF3, leading to immunoadjuvant IFN-β expression.

Comparing four volumetric modulated arc therapy beam arrangements for the treatment of early-stage prostate cancer.

IntroductionThis study compared four different volumetric modulated arc therapy (VMAT) beam arrangements for the treatment of early-stage prostate cancer examining plan quality and the impact on a radiotherapy department's resources.MethodsTwenty prostate cases were retrospectively planned using four VMAT beam arrangements (1) a partial arc (PA), (2) one arc (1A), (3) one arc plus a partial arc (1A + PA) and (4) two arcs (2A). The quality of the dose distributions generated were compared by examining the overall plan quality, the homogeneity and conformity to the planning target volume (PTV), the number of monitor units and the dose delivered to the organs at risk. Departmental resources were considered by recording the planning time and beam delivery time.ResultsEach technique produced a plan of similar quality that was considered adequate for treatment; though some differences were noted. The 1A, 1A + PA and 2A plans demonstrated a better conformity to the PTV which correlated to improved sparing of the rectum in the 60–70 Gy range for the 1A + PA and 2A techniques. The time needed to generate the plans was different for each technique ranging from 13.1 min for 1A + PA to 17.8 min for 1A. The PA beam delivery time was fastest with a mean time of 0.9 min. Beam-on times then increased with an increase in the number of arcs up to an average of 2.2 min for the 2A technique.ConclusionWhich VMAT technique is best suited for clinical implementation for the treatment of prostate cancer may be dictated by the individual patient and the availability of departmental resources.

Comparative effectiveness of aggressive versus nonaggressive treatment among men with early‐stage prostate cancer and differing comorbid disease burdens at diagnosis

This study sought to compare the effectiveness of aggressive versus nonaggressive treatment in reducing cancer-specific mortality for older men with early-stage prostate cancer across differing comorbid disease burdens at diagnosis. In total, the authors sampled 140,553 men aged ≥ 66 years with early-stage prostate cancer who were diagnosed between 1991 and 2007 from the Surveillance, Epidemiology, and End Results-Medicare database. Propensity-adjusted competing-risks regression analysis was used to compare the risk of cancer-specific mortality between men who received aggressive versus nonaggressive treatment among comorbidity subgroups. In propensity-adjusted competing-risks regression analysis, aggressive treatment was associated with a significantly lower risk of cancer-specific mortality among men who had Charlson scores of 0, 1, and 2 but not among men who had Charlson scores ≥ 3 (subhazard ratio, 0.85; 95% confidence interval, 0.62-1.18). The absolute reduction in 15-year cancer-specific mortality between men who received aggressive versus nonaggressive treatment was 6.1%, 4.3%, 3.9%, and 0.9% for men with Charlson scores of 0, 1, 2, and ≥ 3, respectively. Among men who had well-differentiated and moderately-differentiated tumors, aggressive treatment again was associated with a lower risk of cancer-specific mortality for those who had Charlson scores of 0, 1, and 2 but not for those who had Charlson scores ≥ 3 (subhazard ratio, 1.14; 95% confidence interval, 0.70-1.89). The absolute reduction in 15-year cancer-specific mortality between men who received aggressive versus nonaggressive treatment was 3.8%, 3%, 1.9%, and -0.5% for men with Charlson scores of 0, 1, 2, and ≥ 3, respectively. The cancer-specific survival benefit from aggressive treatment for early-stage prostate cancer diminishes with increasing comorbidity at diagnosis. Men with Charlson scores ≥ 3 garner no survival benefit from aggressive treatment.

Clinical Controversies: Proton Therapy for Prostate Cancer

Proton therapy has been used in the treatment of prostate cancer for several decades, and interest surrounding its use continues to grow. Proton-based treatment techniques have evolved significantly over this period, and several centers now routinely use technologies such as pencil-beam scanning. However, whether the theoretical dosimetric advantages of the proton beam translate into clinically meaningful improvements for prostate cancer patients is unknown, and outcomes from single-arm experiences using whole courses of proton beam therapy in the treatment of early-stage prostate cancer have shown mixed results when compared with contemporary intensity-modulated radiotherapy. A randomized trial comparing proton beam therapy with intensity-modulated radiotherapy in early-stage disease has been launched and will be important in defining the role for proton therapy in this setting. We review the available evidence and present the current state of proton beam therapy for prostate cancer.

A new approach to understanding racial disparities in prostate cancer treatment

Previous studies addressing racial disparities in treatment for early-stage prostate cancer have focused on the etiology of undertreatment of black men. Our objective was to determine whether racial disparities are attributable to undertreatment, overtreatment, or both. Using the SEER-Medicare dataset, we identified men 67–84 years-old diagnosed with localized prostate cancer from 1998 to 2007. We stratified men into clinical benefit groups using tumor aggressiveness and life expectancy. Low-benefit was defined as low-risk tumors and life expectancy <10 years; high-benefit as moderate-risk tumors and life expectancy ≥10 years; all others were intermediate-benefit. Logistic regression modeled the association between race and treatment (radical prostatectomy or radiotherapy) across benefit groups. Of 68,817 men (9.8% black and 90.2% white), 56.2% of black and 66.3% of white men received treatment (adjusted odds ratio (OR)=0.65; 95% CI, 0.62–0.69). The percent of low-, intermediate-, and high-benefit men who received treatment was 56.7%, 68.4%, and 79.6%, respectively (P=<0.001). In the low-benefit group, 51.9% of black vs. 57.2% of white patients received treatment (OR=0.74; 95% CI, 0.67–0.81) compared to 57.2% vs. 69.6% in the intermediate-benefit group (OR=0.64; 95% CI, 0.59–0.70). Racial disparity was largest in the high-benefit group (64.2% of black vs. 81.4% of white patients received treatment; OR=0.57; 95% CI, 0.48–0.68). The interaction between race and clinical benefit was significant (P<0.001). Racial disparities were largest among men most likely to benefit from treatment. However, a substantial proportion of both black and white men with a low clinical benefit received treatment, indicating a high level of overtreatment.

Factors Associated with the Adoption of Minimally Invasive Radical Prostatectomy in the United States

Minimally invasive radical prostatectomy has supplanted radical retropubic prostatectomy in popularity despite the absence of strong comparative effectiveness data demonstrating its superiority. We examined the influence of patient, surgeon and hospital characteristics on the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy. Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data we identified 11,732 men who underwent radical prostatectomy from 2003 to 2007. We assessed the contribution of patient, surgeon and hospital characteristics to the likelihood of undergoing minimally invasive radical prostatectomy vs radical retropubic prostatectomy using multilevel logistic regression mixed models. Patient factors (36.7%) contributed most to the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy, followed by surgeon (19.1%) and hospital (11.8%) factors. Among patient specific factors Asian race (OR 1.86, 95% CI 1.27-2.72, p = 0.001), clinically organ confined tumors (OR 2.71, 95% CI 1.60-4.57, p <0.001) and obtaining a second opinion from a urologist (OR 3.41, 95% CI 2.67-4.37, p <0.001) were associated with the highest use of minimally invasive radical prostatectomy while lower income was associated with decreased use of minimally invasive radical prostatectomy. Among surgeon and hospital specific factors, higher surgeon volume (OR 1.022, 95% CI 1.015-1.028, p <0.001), surgeon age younger than 50 years (OR 2.68, 95% CI 1.69-4.24, p <0.001) and greater hospital bed size (OR 1.001, 95% CI 1.001-1.002, p <0.001) were associated with increased use of minimally invasive radical prostatectomy, while solo or 2 urologist practices were associated with decreased use of minimally invasive radical prostatectomy (OR 0.48, 95% CI 0.27-0.86, p = 0.013). The adoption of minimally invasive radical prostatectomy vs radical retropubic prostatectomy is multifactorial, and associated with specific patient, surgeon and hospital related factors. Obtaining a second opinion from another urologist was the strongest factor associated with opting for minimally invasive radical prostatectomy.

Effective Treatment for Early-Stage Prostate Cancer — Possible, Necessary, or Both?

In 2010, prostate cancer was diagnosed in approximately 217,000 men in the United States. More than 90% of patients with newly diagnosed prostate cancer have localized (clinical stage T1 or T2) disease.1 Men with early-stage prostate cancer face the treatment dilemma posed by the urologist Dr. Willet Whitmore: “If treatment for cure is necessary, is it possible? If possible, is it necessary?” The Scandinavian Prostate Cancer Group Study 4 (SPCG-4) has provided important evidence that effective treatment is both necessary and possible for many men with early-stage prostate cancer. In a 2008 report of SPCG-4, radical prostatectomy, as compared with . . .

Highlights of This Issue

The value of neoadjuvant hormone therapy (NHT) before radical prostatectomy, for the treatment of early-stage prostate cancer, is not clear. Here, Sorrentino and colleagues found that NHT boosted IL-7 and IFNγ-inducible protein (IP)-10/CXCL10 expression in the prostate and promoted cytotoxic-effector T cell influx. However, NHT also induced thymus and activation-regulated chemokine (TARC)/CCL17 production in the prostate and draining lymph nodes and increased their Foxp3+CD25+CD127- T regulatory cell content. The concomitant recruitment of cytotoxic-effector and regulatory cells left their intratumoral balance unchanged and did not improve disease-free survival. These findings may help guide treatment decision-making in prostate cancer.The last decade has seen exciting progress in multiple myeloma research, leading to changes in treatment paradigms for the disease. In this issue of CCR Focus, guest editor Kenneth Anderson discusses some of the recent advances in myeloma research and also addresses challenges in translating this progress into better patient care. Topics covered include the underlying molecular biology of multiple myeloma; premalignant forms of the disease and potential prevention strategies; complexities in selecting upfront therapies; myeloma drugs in the pipeline and suggestions for combination therapies; improving the personalization of treatment; and progress in treating bone-related complications.Chondroitin sulfate proteoglycans are a family of extracellular matrix glycoproteins highly upregulated in gliomas. These proteins form large complexes that facilitate tumor growth while limiting the local diffusion of therapeutic agents. In this issue, Dmitrieva and colleagues found that digestion of chondroitin sulfate by bacterial chondroitinase enhanced distribution and spread of oncolytic viruses within the tumor. Furthermore, they showed that an oncolytic virus armed with bacterial chondroitinase had enhanced spread and therapeutic efficacy against gliomas, without increasing tumor invasion or migration. This approach against the tumor microenvironment shows promise as a therapeutic strategy for glioma.Ovarian clear cell carcinomas (OCCC) are a drug-resistant and aggressive type of epithelial ovarian cancer. In this issue, Tan and colleagues revealed that OCCCs are heterogeneous at the genomic level by performing highresolution microarray-based comparative genomic hybridisation. Unsupervised hierarchical clustering analysis identified two distinct clusters of OCCCs with distinct clinical outcomes, independent of their histologic features. Multivariate analysis showed that suboptimal debulking surgery and genomic cluster were independent predictors of progression-free survival. These findings provide evidence that OCCCs are genomically heterogeneous despite having similar histologic features and that this genomic heterogeneity is clinically significant.

From bad to worse: comorbidity severity and quality of life after treatment for early-stage prostate cancer

Commonly used measures of comorbidity assess comorbidity number and type but not severity. We sought to evaluate the impact of comorbidity severity on longitudinal health-related quality of life (HRQOL) in men treated with radical prostatectomy (RP) or radiation therapy (RT) using the Total Illness Burden Index for prostate cancer (TIBI-CaP). We sampled 738 men with non-metastatic prostate cancer treated with RP or RT from the Cancer of the Prostate Strategic Urologic Research Endeavor registry. We examined the impact of comorbidity severity on generic and disease-specific HRQOL at baseline and at 6, 12, 18 and 24 months post-treatment. Men with worse TIBI-CaP comorbidity had significantly lower baseline and post-treatment HRQOL in all domains at all time points. In a multivariate model, men with moderate or severe TIBI-CaP comorbidity had significantly worse HRQOL scores at 12 and 24 months after treatment in all domains except sexual and urinary function (P<0.05); in these domains, severe comorbidity was predictive of lower HRQOL (P<0.05). Comorbidity groups had similar absolute declines in HRQOL from baseline to 6 and 24 months after treatment. Although comorbidity groups experienced similar long-term declines from baseline HRQOL after treatment, men with more severe comorbidity had significantly lower baseline scores and therefore poorer long-term HRQOL.

A Review of Low-Dose-Rate Prostate Brachytherapy—Techniques and Outcomes

Prostate cancer is the most common male cancer in the United States and the second leading cause of male cancer death. The main therapeutic modalities for the treatment of prostate cancer are surgery, external beam radiation therapy, hormonal therapy, and brachytherapy. In recent years, brachytherapy has been increasingly utilized for the treatment of early-stage prostate cancer. Technological advances, including improvements in imaging, planning, and postimplant quality assessment by dosimetry have led to widespread use of brachytherapy. Outcomes for prostate brachytherapy have been shown to be equivalent, in selected patients, to those of other treatment modalities for prostate cancer, including radical prostatectomy and external beam radiation therapy. Further, prostate brachytherapy has quality-of-life benefits in comparison to these other treatment modalities, particularly in the domain of sexual function. This paper describes the history of low-dose rate brachytherapy; current techniques for brachytherapy implantation and postoperative dosimetric evaluation; recent outcomes studies; recent quality-of-life analyses; and current and future prostate brachytherapy developments, including open clinical trials. As research in prostate brachytherapy continues, it is likely that this modality will play an increasingly important role in the treatment of early-stage prostate cancer patients in the future.