Monotherapy For Prostate Cancer Research Articles

Incidence of subsequent primary cancers and radiation-induced subsequent primary cancers after low dose-rate brachytherapy monotherapy for prostate cancer in long-term follow-up

BackgroundAs aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs).MethodsDuring the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated.ResultsDuring the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively.ConclusionThe crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.

A radiobiological study of the schemes with a low number of fractions in high-dose-rate brachytherapy as monotherapy for prostate cancer

PurposeSchemes with high doses per fraction and small number of fractions are commonly used in high-dose-rate brachytherapy (HDR-BT) for prostate cancer. Our aim was to analyze the differences between published clinical results and the predictions of radiobiological models for absorbed dose required in a single fraction monotherapy HDR-BT.Material and methodsPublished HDR-BT clinical results for low- and intermediate-risk patients with prostate cancer were revised. For 13 clinical studies with 16 fractionation schedules between 1 and 9 fractions, a dose-response relation in terms of the biochemical control probability (BC) was established using Monte Carlo-based statistical methods.ResultsWe obtained a value of α/β = 22.8 Gy (15.1-60.2 Gy) (95% CI) much larger than the values in the range 1.5-3.0 Gy that are usually considered to compare the results of different fractionation schemes in prostate cancer radiotherapy using doses per fraction below 6 Gy. The doses in a single fraction producing BC = 90% and 95% were 22.3 Gy (21.5-24.2 Gy) and 24.3 Gy (23.0-27.9 Gy), respectively.ConclusionsThe α/β obtained in our analysis of 22.8 Gy for a range of dose per fraction between 6 and 20.5 Gy was much greater than the one currently estimated for prostate cancer using low doses per fraction. This high value of α/β explains reasonably well the data available in the region of high doses per fraction considered.

87 High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer: One Fraction May Not Be Enough

87 High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer: One Fraction May Not Be Enough

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

High-dose-rate brachytherapy as monotherapy for prostate cancer: The impact of cellular repair and source decay

PurposeThis work quantifies the influence of intrafraction DNA damage repair and cellular repopulation on biologically effective dose (BED) in Ir-192 high-dose-rate brachytherapy for prostate cancer. In addition, it examines the effect of source-decay–induced BED variation for patients treated at different time points in a source exchange cycle. Materials and MethodsCurrent fractionation schemes are based on simplified-form BED = nd(1 + d/(α/β)), which assumes that intrafraction repair, interfraction repair, and repopulation are negligible. We took accepted radiobiological parameters of Tk, Tp, and α from the recommendations of the AAPM TG-137, and recalculated the full-form BED. Fraction times were normalized to require 15 min for 20 Gy at 10 Ci. Calculations were carried out for both α/β = 1.5 and 3 Gy. ResultsAfter accounting for intrafraction repair, interfraction repair, and/or repopulation, full-form BED calculations showed significant values, as compared with simplified-form BED. For 1-fraction 20 Gy fractionation, the full-form BED was only 64–82% of the simplified-form BED. Dose protraction effects were milder for smaller prescriptions (6 Gy/Fx), where full form was 87–94%. With regard to source decay, BED varied >20% for patients treated at the beginning and the end of a source exchange cycle for 20 Gy single-fraction prescription. ConclusionsRepair and repopulation can be significant in monotherapy high-dose-rate for prostate cancer. As fractionation schemes are established, the simplified BED calculation may not be appropriate. Investigators should consider evaluating BED as a range rather than a discrete value when presenting results unless source activity is explicitly incorporated as well.

MRI-Guided Focal HDR Brachytherapy as Monotherapy for Prostate Cancer: Early Feasibility and Quality of Life Study

MRI-Guided Focal HDR Brachytherapy as Monotherapy for Prostate Cancer: Early Feasibility and Quality of Life Study

PV-0146 RTOG versus CTCAE score: reporting toxicity of HDR brachytherapy Monotherapy for prostate cancer

PV-0146 RTOG versus CTCAE score: reporting toxicity of HDR brachytherapy Monotherapy for prostate cancer

OC-0282 HDR brachytherapy Monotherapy for prostate cancer: a one-day schedule phase II trial acute toxicity

OC-0282 HDR brachytherapy Monotherapy for prostate cancer: a one-day schedule phase II trial acute toxicity

Treatment patterns of high-dose-rate and low-dose-rate brachytherapy as monotherapy for prostate cancer.

PurposeMonotherapy with high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy are both recommended modalities for prostate cancer. The choice between HDR and LDR is dependent on patient, physician, and hospital preferences. We sought to identify treatment patterns and factors associated with receipt of HDR or LDR monotherapy.Material and methodsWe queried the National Cancer Database (NCDB) for patients with localized low- or intermediate-risk prostate cancer treated with HDR or LDR monotherapy. Descriptive statistics were used to analyze patterns of HDR vs. LDR. Patient characteristics were correlated with HDR vs. LDR using multivariable logistic regression.ResultsWe identified 50,326 patients from 2004-2014: LDR 37,863 (75.2%) vs. HDR 12,463 (24.8%). Median follow-up was 70.3 months. The overall use of monotherapy declined over time. HDR application declined relative to LDR. In 2004, 27.0% of cases were HDR compared to 19.2% in 2014. Factors associated with increased likelihood of HDR on multivariable analysis included: increasing age (OR: 1.01, 95% CI: 1.01-1.01), cT2c disease (OR: 1.25, 95% CI: 1.11-1.41), treatment at an academic center (OR: 2.45, 95% CI: 2.24-2.65), non-white race (OR: 1.34, 95% CI: 1.27-1.42), and income > $63,000 (OR: 1.73, 95% CI: 1.59-1.88). LDR was more common in 2010-2014 (OR: 0.59, 95% CI: 0.54-0.65), Charlson-Deyo comorbidity index > 0 (OR: 0.89, 95% CI: 0.84-0.95), and for patients receiving hormone therapy (OR: 0.88, 95% CI: 0.83-0.93). No difference in prostate-specific antigen (PSA) or Gleason score and receipt of HDR vs. LDR was observed. Mean overall survival was 127.0 months for HDR and 125.4 for LDR, and was not statistically different.ConclusionsWe observed an overall decrease in brachytherapy (BT) monotherapy use since 2004 for localized prostate cancer. Despite similar survival outcomes, the use of HDR monotherapy declined relative to LDR.

High-Dose-Rate Brachytherapy As Monotherapy for Prostate Cancer: A Meta-analysis of Biochemical Control Rates and Dose Fractionation

To analyze published biochemical control data for different fractionation schemes obtained using high-dose-rate brachytherapy as monotherapy for prostate cancer and to determine optimal dose per fraction by including the effect of intrafraction DNA repair. A meta-analysis was conducted on 31 studies, published between 2009-2017, which estimated biochemical control using Kaplan-Meier (KM) method for 3692 patients: 1413 low-risk (LR), 1161 intermediate-risk (IR), and 470 high risk (HR) (648 unspecified). In these studies, risk was classified using NCCN standards and biochemical control was defined using the Phoenix definition. We compared reported biochemical control as a function of biologically effective dose (BED) calculated using various methods. To account for intrafraction repair, BED was calculated with and without the Lea-Catcheside dose protraction factor for a range of source activities and dose rates. Clinical data suggests prostate cancer has a fast rate of repair which is on the same order of magnitude of delivery time, especially for single fractions. Biologically optimal dose per fraction for a given number of fractionation schemes was determined based on BED. Reported biochemical control rates were ≥ 85% for LR patients in nearly all studies, with the notable exception of a 1-fraction study with biochemical control rates of 66% at a KM projection of 6 years. Among the 31 studies, fractionations ranged from 1 to 9 fractions with BEDs of 180-299 Gy (α/β=1.5 Gy) and 108-167 Gy (α/β=3 Gy). BED was reduced by up to 31.9% (α/β=1.5 Gy) and 29.5% (α/β=3 Gy) for 1-fraction delivery when including corrections for intrafraction repair. The poor biochemical control seen with single fractions may be attributed to underestimating the effect of intrafraction repair. Table 1 shows calculated prescription doses required to match a BED of 207 Gy (α/β=1.5 Gy) including intrafraction repair for the 6x7 Gy scheme (biochemical control of 94% at 8 years). To achieve this BED, a 1-fraction delivery may require 21 (α/β=1.5 Gy) or 22.3 Gy (α/β=3 Gy). Prescription doses may need to be even higher for single fractions as the effects of tumor hypoxia and reoxygenation are neglected. In general, excellent clinical outcomes are achievable with HDR brachytherapy as monotherapy for prostate cancer patients – this study focused on LR. The relatively poor biochemical control rates observed for single fractions suggests multi-fraction HDR brachytherapy may be more clinically effective. If single fractions are used, cautious dose escalation should be considered to improve biochemical control.Abstract 3482# of FxClinically Used [Gy/Fx]Reported Biochemical Control Rates for Low-Risk (LR) Prostate Cancer PatientsRecommended Rx Doses [Gy/Fx]11966% @ 6 y21212-13.592% @ 5 y13.5310-11.585% @ 5 y10.548.5-9.594% @ 5 y966-7.594% @ 8 y776.5N/A [IR patients only]6.586N/A [IR patients only]69685% @ 5 y5.5 Open table in a new tab

HDR Monotherapy in Prostate Cancer: Radiobiological Considerations When Determining Biologically Effective Dose in Clinical Trials

HDR Monotherapy in Prostate Cancer: Radiobiological Considerations When Determining Biologically Effective Dose in Clinical Trials

EP-1768: What is the proper dose in single fraction HDR brachytherapy as monotherapy for prostate cancer?

EP-1768: What is the proper dose in single fraction HDR brachytherapy as monotherapy for prostate cancer?

814 - Nationwide multicenter retrospective study on high-dose-rate brachytherapy as monotherapy for prostate cancer

814 - Nationwide multicenter retrospective study on high-dose-rate brachytherapy as monotherapy for prostate cancer

High-dose rate brachytherapy as monotherapy in prostate cancer: A systematic review of its safety and efficacy

ContextHigh-dose rate brachytherapy (HDR-BT) is an increasingly popular treatment for patients with localized prostate cancer (PC). ObjectiveTo assess the safety and efficacy of HDR-BT as monotherapy in PC. Acquisition of evidenceA systematic literature review was conducted through searches on MEDLINE (PubMed), Cochrane Library, CDR, ClinicalTrials and EuroScan. We assessed safety and efficacy indicators. Summary of the evidenceWe selected 2 reviews and 12 uncontrolled studies, included in these 2 reviews. In terms of efficacy, local control in 6 studies was 97–100%. The biochemical progression-free survival varied as follows: 85–100% for low risk and 79–92% for high risk. Survival free of metastases was >95% at 8 years, except in one study where the survival rate was 87% at 5 years. The overall survival was ≥95% in 8 studies. In terms of safety, most of the studies recorded acute and long-term genitourinary and gastrointestinal complications, especially grade ≥2. Only 3 studies found grade 4 complications. All studies, except for one without complications, observed genitourinary complications that were more frequent and severe than the gastrointestinal complications. Two studies assessed the quality of life and showed an initial reduction in various domains and subsequent partial or total recovery, except in the sexual domain. ConclusionsHDR-BT is effective as monotherapy, especially in cases of low to intermediate risk. There is insufficient information on high-risk patients. The short to medium-term toxicity was acceptable. Further research needs to be funded to provide more information on the long-term safety and efficacy of this treatment.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27Gy/2 fractions for 69 patients (13%), 45.5Gy/7 fractions for 168 (32%), 49Gy/7 fractions for 149 (28%), 54Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1year, 112 (21%) for 1-3years, and 54 (10%) for >3years. Median follow-up time was 5.9years (range, 0.4-18.1years), with a minimum of 2years for surviving patients. After 5years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

Oncologic Outcomes After Robot-assisted Radical Prostatectomy: A Large European Single-centre Cohort with Median 10-Year Follow-up

BackgroundRobot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (>5 yr) oncologic efficacy. ObjectiveTo evaluate long-term oncologic outcomes following RARP. Design, setting, and participantsProspective cohort study of 885 patients who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single European centre and followed up until 2016. InterventionRARP as monotherapy. Outcome measurements and statistical analysisBiochemical recurrence (BCR)–free survival (BCRFS), salvage therapy (ST)–free survival (STFS), prostate cancer–specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method, and event-time distributions were compared using the log-rank test. Variables predictive of BCR and ST were identified using Cox proportional hazards models. Results and limitationsWe identified 167 BCRs, 110 STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS, CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median follow-up of 10.5 yr. On multivariable analysis, the strongest independent predictors of both BCR and ST were preoperative Gleason score, pathological T stage, positive surgical margins (PSMs), and preoperative prostate-specific antigen. PSM >3mm/multifocal but not ≤3mm independently affected the risk of both BCR and ST. Study limitations include a lack of centralised histopathologic reporting, lymph node and post-operative tumour volume data in a historical cohort, and patient-reported outcomes. ConclusionsRARP appears to confer effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by ≤3mm PSM, but further follow-up is required to determine any impact on CSS. Patient summaryRobot-assisted surgery for prostate cancer is effective 10 yr after treatment. Very small (<3mm) amounts of cancer at the cut edge of the prostate do not appear to impact on recurrence risk and the need for additional treatment, but it is not yet known whether this affects the risk of death from prostate cancer.

Outcome of radical prostatectomy in primary circulating prostate cell negative prostate cancer.

IntroductionAround 90% of prostate cancers detected using the serum prostate specific antigen (PSA) as a screening test are considered to be localised. However, 20–30% of men treated by radical prostatectomy experience biochemical failure within two years of treatment. The presence of primary circulating prostate cells (CPCs) in the blood of these men implies a dissemination of the tumour and could indicate a greater risk of treatment failure.ObjectiveTo evaluate the use of the number of primary CPCs detected before surgery in the prediction of biochemical failure at ten years.HypothesisThe dissemination of cancer cells to distant sites will determine the patient’s prognosis. The absence of primary CPCs in men undergoing radical prostatectomy for prostate cancer may imply a less aggressive disease and therefore could be utilised as a prognostic factor to predict biochemical failure after surgery.Methods and patientsA single-centre observational study of a cohort of 285 men who underwent radical prostatectomy as monotherapy for prostate cancer, in whom the number of CPCs prior to treatment was determined, and who were followed up for ten years to determine biochemical failure. A Cox proportional risks with polynomial fractions analysis was used to predict biochemical failure based on the number of primary CPCs detected. A decision curve analysis was performed for the model obtained.ResultsKaplan–Meier curves for biochemical free survival at ten years was 47.34% (95% CI 38.71–55.48%). It is important to note that in CPC negative men, the ten years Kaplan–Meier biochemical-free survival was 90.35% (95% CI 75.0–96.27) whereas in men who were primary CPC positive, the biochemical free survival rate was 30.00% (95% CI 20.34–40.60%).The Coxs´model to predict biochemical failure using transformed data with a power of minus one for the number of primary CPCs detected, showed a Harrell´s C concordance index of 0.74 and a decision analysis curve showing a net benefit of CPC detection over other risk factors to predict biochemical failure.ConclusionsThe number of primary CPCs detected before surgery permits a good prediction of subsequent biochemical failure in men undergoing radical prostatectomy as monotherapy for prostate cancer. Men negative for primary CPCs have a biochemical-free survival of over 90% at ten years and should be considered for curative surgery.

Braquiterapia de alta tasa de dosis como monoterapia en cáncer de próstata: una revisión sistemática sobre eficacia y seguridad

ContextHigh-dose rate brachytherapy (HDR-BT) is an increasingly popular treatment for patients with localised prostate cancer (PC). ObjectiveTo assess the safety and efficacy of HDR-BT as monotherapy in PC. Acquisition of evidenceA systematic literature review was conducted through searches on MEDLINE (PubMed), Cochrane Library, CDR, ClinicalTrials and EuroScan. We assessed safety and efficacy indicators. Summary of the evidenceWe selected 2 reviews and 12 uncontrolled studies, included in these 2 reviews. In terms of efficacy, local control in 6 studies was 97-100%. The biochemical progression-free survival varied as follows: 85-100% for low risk and 79-92% for high risk. Survival free of metastases was >95% at 8 years, except in one study where the survival rate was 87% at 5 years. The overall survival was ≥95% in 8 studies. In terms of safety, most of the studies recorded acute and long-term genitourinary and gastrointestinal complications, especially grade ≥2. Only 3 studies found grade 4 complications. All studies, except for one without complications, observed genitourinary complications that were more frequent and severe than the gastrointestinal complications. Two studies assessed the quality of life and showed an initial reduction in various domains and subsequent partial or total recovery, except in the sexual domain. ConclusionsHDR-BT is effective as monotherapy, especially in cases of low to intermediate risk. There is insufficient information on high-risk patients. The short to medium-term toxicity was acceptable. Further research needs to be funded to provide more information on the long-term safety and efficacy of this treatment.

Limited improvement of incorporating primary circulating prostate cells with the CAPRA score to predict biochemical failure-free outcome of radical prostatectomy for prostate cancer

ObjectiveTo establish a prediction model for early biochemical failure based on the Cancer of the Prostate Risk Assessment (CAPRA) score, the presence or absence of primary circulating prostate cells (CPC) and the number of primary CPC (nCPC)/8ml blood sample is detected before surgery. Patients and methodsA prospective single-center study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinical-pathological findings were used to calculate the CAPRA score. Before surgery blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen and P504S, and the presence or absence of CPCs and the number of cells detected/8ml blood sample was registered. Patients were followed up for up to 5 years; biochemical failure was defined as a prostate-specific antigen>0.2ng/ml. The validity of the CAPRA score was calibrated using partial validation, and the fractional polynomial Cox proportional hazard regression was used to build 3 models, which underwent a decision analysis curve to determine the predictive value of the 3 models with respect to biochemical failure. ResultsA total of 267 men participated, mean age 65.80 years, and after 5 years of follow-up the biochemical-free survival was 67.42%. The model using CAPRA score showed a hazards ratio (HR) of 5.76 between low and high-risk groups, that of CPC with a HR of 26.84 between positive and negative groups, and the combined model showed a HR of 4.16 for CAPRA score and 19.93 for CPC. Using the continuous variable nCPC, there was no improvement in the predictive value of the model compared with the model using a positive-negative result of CPC detection. The combined CAPRA-nCPC model showed an improvement of the predictive performance for biochemical failure using the Harrell׳s C concordance test and a net benefit on DCA in comparison with either model used separately. The use of primary CPC as a predictive factor based on their presence or absence did not predict aggressive disease or biochemical failure. ConclusionAlthough the use of a combined CAPRA-nCPC model improves the prediction of biochemical failure in patients undergoing radical prostatectomy for prostate cancer, this is minimal. The use of the presence or absence of primary CPCs alone did not predict aggressive disease or biochemical failure.

Fractionated high-dose-rate brachytherapy as monotherapy in prostate cancer: Does implant displacement and its correction influence acute and late toxicity?

PurposeIn fractionated high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) with one implant for several fractions, dose delivery relies on reproducibility of catheter positions. However, caudal displacement of implanted catheters does occur between fractions and needs to be corrected. Our protocol prescribes correction of displacements > 3 mm. We investigated whether displacement and its corrections influence acute and late toxicity incidences. Methods and MaterialsWe analyzed 162 PCa patients treated with HDR-BT monotherapy between 2007 and 2013. The implant remained in situ between the 4 fractions. Catheter displacement was assessed before each fraction using lateral X-ray images and corrected if needed. Genitourinary (GU) and gastrointestinal (GI) acute and late toxicities were assessed using clinical record forms and patient self-assessment questionnaires. ResultsImplant displacement corrections (DC) were needed in 71 patients (43.8%) whereas no DCs were needed in 91 patients (56.2%). No statistically significant differences were seen in acute and late grade ≥ 2 GU and GI toxicity incidences between DC and no DC groups. The maximum displacement nor the number of corrections had any influence on toxicity. ConclusionsThe occurrence and subsequent correction of implant displacements exceeding 3 mm during fractionated HDR-BT monotherapy for PCa did not lead to increased incidences of acute or late GU and GI toxicity. This indicates that our clinical protocol to correct displacements > 3 mm results in safe treatment regarding organ at risk toxicity.