5-year bPFS Research Articles

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer.

Phosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer. Patients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant. Ninety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial.

Multi-Institutional Analysis of Metastasis Directed Therapy with or without Androgen Deprivation Therapy in Oligometastatic Castration Sensitive Prostate Cancer.

Several prospective trials in oligometastatic castration sensitive prostate cancer (omCSPC) have shown metastasis-directed therapy (MDT) can delay time to progression and initiation of androgen deprivation therapy (ADT) compared to observation. However, the optimal integration of ADT with MDT remains unclear. Here we report a multi-national, multi-institutional retrospective cohort of omCSPC treated with MDT to characterize the long-term outcomes of patients treated with MDT alone or in combination with ADT. Patients with a controlled primary site and omCSPC (defined as ≤ 5 lesions on conventional imaging) treated with MDT with or without concurrent ADT and with at least 36 months follow-up were retrospectively screened across 13 institutions. The primary endpoints included biochemical progression free survival (bPFS) and radiographic progression free survival (rPFS) calculated using Kaplan-Meier method and stratified by treatment group (MDT alone vs MDT + ADT). Multivariable Cox regression was performed adjusted for variables found to be prognostic on univariate analysis. Among 414 patients screened, a total of 263 patients treated between 2003 and 2018 met inclusion criteria and included. Of these, 105 received MDT alone and 158 received MDT+ADT, with median follow-up of 49.5 and 54.5 months, respectively. The majority were metachronous (90%) and had bone lesions (60%). Median ADT duration was 21.3 months (IQR 12.0- 31.9). Patients who received ADT vs. no ADT had poorer prognostic features including 23% vs. 1% synchronous (p<0.001), and 55% vs 40% Gleason 8-10 (p = 0.012). ADT use was associated with a better 5-year bPFS 24% vs 11% (p<0.0001) and rPFS 41% vs 29% (p<0.001). On multivariable Cox regression adjusting for post-MDT PSA nadir and salvage therapy, ADT use maintained significance for both bPFS (HR 0.51 (0.36, 0.71), p<0.001) and rPFS (HR 0.67, 95% CI 0.46-0.96, p = 0.03). Long-term outcomes with MDT alone suggest a small proportion of patients experience sustained disease control. The addition of ADT appears to improve rPFS, however prospective studies are needed in order to allow for personalization of care in patients with omCSPC.

Outcomes in Locally Advanced Non-Metastatic Prostate Cancer Presenting with Low PSA at Diagnosis.

Men with low serum prostate-specific antigen (PSA) and high Gleason grade group (GGG) are thought to have poor outcomes compared to high PSA secretors. However, there is limited outcome data to support this. We report clinical outcomes from a single-institutional cohort of men presenting with locally advanced prostate cancer but low serum PSA. Data from electronic database of a UK tertiary cancer center was acquired for men with histological diagnosis of prostate adenocarcinoma, GGG 4 or 5, stage ≥cT3a, and PSA <10ug/L at diagnosis. Men with metastatic disease, or prior androgen deprivation therapy (ADT) were excluded. Biochemical progression was defined as per Phoenix criteria (PSA > nadir+2) for primary radiotherapy, or PSA >0.2 ug/L after primary prostatectomy (and post-operative radiotherapy, if received). Overall survival (OS, from date of diagnosis to death), metastasis-free survival (MFS, from diagnosis to first recorded metastasis or death), and biochemical progression free survival (bPFS, from diagnosis to biochemical progression or death) were estimated by Kaplan Meier method, and multivariable analysis performed using Cox proportional hazards method. Medical records of 7,200 men presenting with non-metastatic prostate cancer from 2013 to 2021 were screened, of which 270 men satisfying the eligibility criteria were included for this study. Initial analysis of 123 men shows median PSA at presentation 7.1 ug/L (IQR 5.6-8.5), and median age 70 years (IQR 65-75). Histology was GGG 4 in 47.6% and 5 in 52.4%. Tumor stage was cT3a in 56.6%, cT3b in 36.9%, and T4 in 6.6%. Pelvic nodes were involved in 5% patients. Majority (83.7%) were treated with radical radiotherapy (external beam alone 64.2%, brachytherapy boost 19.5%), with 24 months ADT; 11.4% underwent radical prostatectomy, and 4.9% received ADT alone. Three men (2.4%) received docetaxel, and one received abiraterone. At a median follow up of 66 months (IQR 27-77), 36 (29.3%) patients had biochemical failure. Total 23 (18.6%) patients had metastases at recurrence, which were visceral in 4%, bone-only in 10%, and nodal-only in 4%. Total 38 (30.6%) patients had died, 23% with prostate cancer and 11% due to other causes. Five-year bPFS was 65.9%, MFS 69.0%, and OS was 77.4%. GGG 5 (versus 4) was associated with significantly worse 5-year bPFS (59.4% vs 73.9%, HR 1.8, 95% CI 1.0-3.2, p = 0.05) and MFS (59.2% vs 81.6%, HR 2.2, 1.2-4.2, p = 0.02). On multivariable analysis including age and PSA at diagnosis, only GGG 5 was associated with worse bPFS (HR 1.8, 1.0-3.3, p = 0.05) and MFS (HR 2.42, 1.25-4.67, p = 0.009). Men with low secreting but high Gleason grade group prostate cancer are a relatively rare group with poor clinical outcomes despite being non-metastatic. Ongoing work (expected completion June 2023) will analyze remaining cases, and compare outcomes within an expanded multicentric cohort with matched controls having elevated PSA at presentation.

Salvage Whole-Pelvic Radiation and Long-Term Androgen-Deprivation Therapy in the Management of High-Risk Prostate Cancer: Long-Term Update of the McGill 0913 Study.

To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT (LT-ADT). From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 μg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.

Impact of prostate radiotherapy on survival outcomes in clinically node-positive prostate cancer: A multicentre retrospective analysis

PurposeTo evaluate clinical outcomes for cN1M0 prostate cancer treated with varied modalities. Materials and methodsMen with radiological stage cN1M0 prostate cancer on conventional imaging, treated from 2011-2019 with various modalities across four centres in the UK were included. Demographics, tumour grade and stage, and treatment details were collected. Biochemical and radiological progression-free survival (bPFS, rPFS) and overall survival (OS) were estimated using Kaplan Meier analyses. Potential factors impacting survival were tested with univariable log-rank test and multivariable Cox-proportional hazards model. ResultsTotal 337 men with cN1M0 prostate cancer were included, 47% having Gleason grade group 5 disease. Treatment modalities included androgen deprivation therapy (ADT) in 98.9% men, either alone (19%) or in combinations including prostate radiotherapy (70%), pelvic nodal radiotherapy (38%), docetaxel (22%), or surgery (7%). At median follow up of 50 months, 5-year bPFS, rPFS, and OS were 62.7%, 71.0%, and 75.8% respectively. Prostate radiotherapy was associated with significantly higher bPFS (74.1% vs 34.2%), rPFS (80.7% vs 44.3%) and OS (86.7% vs 56.2%) at five years (log rank p < 0.001 each). On multivariable analysis including age, Gleason grade group, tumour stage, ADT duration, docetaxel, and nodal radiotherapy, benefit of prostate radiotherapy persisted for bPFS [HR 0.33 (95% CI 0.18–0.62)], rPFS [HR 0.25 (0.12–0.51)], and OS [HR 0.27 (0.13–0.58)] (p < 0.001 each). Impact of nodal radiotherapy or docetaxel was not established due to small subgroups. ConclusionAddition of prostate radiotherapy to ADT in cN1M0 prostate cancer yielded improved disease control and overall survival independent of other tumour and treatment factors.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients. PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment. A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL. The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Long-term prognosis and prognostic factors of brachytherapy and propensity score matched comparisons of the outcomes between brachytherapy and radical prostatectomy: a retrospective cohort study.

To report outcomes of patients undergoing brachytherapy (BT), investigate factors associated with biochemical progression-free survival (bPFS) and to compare its long-term prognosis with that of radical prostatectomy (RP) in localized prostate cancer. The clinical data of 87 elderly patients with localized prostate cancer who underwent BT at Huadong Hospital affiliated to Fudan University from January 2009 to December 2016 were retrospectively analyzed. Patient prognoses and associated factors were investigated using univariate and multivariate Cox regression models. The clinical data of the 142 patients with localized prostate cancer who underwent RP during the same period were also collected. By using propensity score matching (PSM), the 42 patients who underwent BT were matched to 42 patients who underwent RP, and the differences in the survival curves were investigated using the Kaplan-Meier method. The median follow-up period of the patients who underwent BT was 101 months. The 5- and 10-year overall survival (OS) rates of the patients who underwent BT were 82.8% and 64.0%, respectively, while the 5- and 10-year bPFS rates were 97.2% and 87.5%, respectively. The preoperative clinical Tumor (T) stage was identified as a prognostic factor of bPFS, as patients who underwent BT whose clinical stage was T3 had a worse prognosis than those whose clinical stage was T1-T2 (HR =0.097, P=0.049). After PSM, the average follow-up time of the BT group was 90 months and that of the RP group was 94 months. No significant differences in bPFS or cause-specific survival were observed between the 2 groups. The OS of the RP group was significantly higher than that of the BP group (P=0.030). Among the patients with a prostate volume >35 mL, those who underwent BT had significantly higher pPFS than those who underwent RP (P=0.041). In the localized prostate cancer, BT and RP offered similar oncological control in the localized prostate cancer. Stage T3 prostate cancer who undergo BT was associated with worse biochemical failure and was the only variable significantly predictive of biochemical recurrence.

Salvage Radiotherapy Plus Androgen Deprivation Therapy for High-Risk Prostate Cancer with Biochemical Failure after High-Intensity Focused Ultrasound as Primary Treatment.

We conduct a retrospective analysis of salvage radiotherapy plus androgen deprivation therapy (SRT+ADT) for high-risk prostate cancer patients with biochemical failure after high-intensity focused ultrasound (HIFU) as the primary treatment. A total of 38 patients, who met the criteria of biochemical failure and were consecutively treated with SRT+ADT, were enrolled. All patients received intensity modulated radiotherapy with a median dose of 70 Gy to the clinical target volume. ADT was given before, during or after the course of SRT with the duration of ≦6 months (n = 14), 6–12 months (n = 12) or >12 months (n = 12). The median follow-up was 45.9 months. A total of 10 (26.3%) patients had biochemical failure after SRT+ADT. The cumulative 5-year biochemical progression free survival (b-PFS) and overall survival (OS) rate was 73.0% and 80.3%, respectively. A nadir prostate-specific antigen (nPSA) value 0.02 ng/mL was observed to predict the b-PFS in multivariate analysis. The 5-year b-PFS was 81.6% for those with nPSA < 0.02 compared with 25.0% with nPSA ≧ 0.02. The adverse effects related to SRT+ADT were mild in most cases and only three (8%) patients experienced grade 3 urinary toxicities. For high-risk prostate cancer after HIFU as primary treatment with biochemical failure, our study confirms the feasibility of SRT+ADT with high b-PFS, OS and low toxicity.

Biochemical recurrence related metabolic novel signature associates with immunity and ADT treatment responses in prostate cancer.

Prostate cancer (PCa) is a unique cancer from a metabolic perspective. Androgen receptor assumes a vital part in normal and malignant prostate cells regarding almost all aspects of cell metabolism, such as glucose, fat, amino acids, nucleotides, and so on. We used The Cancer Genome Atlas database as training set, Memorial Sloan-Kettering Cancer Center cohort as validation set, and Gene Expression Omnibus database (GSE70769) as test set to identify the optimal prognostic signature. We evaluated the signature in terms of biochemical progression-free survival (bPFS), ROC curve, clinicopathological features, independent prognostic indicators, tumor microenvironment, and infiltrating immune cells. Nomogram was built dependent on the results of cox regression analyses. GSEA algorithm was used to evaluate differences in metabolism. The signature's prediction of androgen deprivation therapy (ADT) response was validated based on two groups of basic cytological experiments treat with ADT (GSE143408 and GSE120343) and the transcriptional information of pre-ADT/post-ADT of six local PCa patients. We finally input four screened genes into the stepwise regression model to construct metabolism-related signature. The signature shows good prediction performance in training set, verification set, and test set. A nomogram based on the PSA, Gleason score, T staging, and the signature risk score could predict 1-, 3-, and 5-year bPFS with the high area under curve values. Based on gene-set enrichment analysis, the characteristics of four genes signature could influence some important metabolic biological processes of PCa and were serendipitously found to be significantly related to androgen response. Subsequently, two cytological experimental data sets and our local patient sequencing data set verified that the signature may be helpful to evaluate the therapeutic response of PCa to ADT. Our systematic study definite a metabolism-related gene signature to foresee prognosis of PCa patients which might add to individual prevention and treatment.

Five Year Results of Short Course Complete Androgen Blockade With Abiraterone Acetate and LHRH Agonist for Unfavorable Intermediate and Favorable High Risk Prostate Cancer

Purpose/Objective(s)Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial.Materials/Methods37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life.ResultsEnrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter.ConclusionFor select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered. Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial. 37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life. Enrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter. For select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered.

Five-year outcomes of stereotactic body radiation therapy (SBRT) for prostate cancer: the largest experience in China

ObjectiveTo evaluate the efficacy and safety of SBRT for localized prostate cancer (PCa) with CyberKnife in China. Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China.MethodsIn this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray Inc., Sunnyvale, USA) from October 2012 to July 2019. Follow-up was performed every 3 months for efficacy and toxicity evaluation. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, respectively. Factors predictive of bPFS were identified with COX regression analysis.Results133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of NCCN risk classification) with a median age of 76 years (range 54–87 years) received SBRT. The median dose was 36.25 Gy (range 34–37.5 Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6%, respectively. Urinary symptoms were all alleviated after SBRT. All patients tolerated SBRT with 1 (0.8%) patient reporting grade-3 acute and 1 (0.8%) patient reporting grade-3 late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis.ConclusionSBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.

An external validation of the Candiolo nomogram in a cohort of prostate cancer patients treated by external\u2010beam radiotherapy

Backgroundthe aim of this study is to perform an external validation for the Candiolo nomogram, a predictive algorithm of biochemical and clinical recurrences in prostate cancer patients treated by radical Radiotherapy, published in 2016 on the journal “Radiation Oncology”.Methods561 patients, treated by Radiotherapy with curative intent between 2003 and 2012, were classified according to the five risk-classes of the Candiolo nomogram and the three risk-classes of the D’Amico classification for comparison. Patients were treated with a mean prostatic dose of 77.7 Gy and a combined treatment with Androgen-Deprivation-Therapy in 76% of cases. The end-points of the study were biochemical-progression-free-survival (bPFS) and clinical-Progression-Free-Survival (cPFS). With a median follow-up of 50 months, 56 patients (10%) had a biochemical relapse, and 30 patients (5.4%) a clinical progression. The cases were divided according to D’Amico in low-risk 21%, intermediate 40%, high-risk 39%; according to Candiolo very-low-risk 24%, low 37%, intermediate 24%, high 10%, very-high-risk 5%. Statistically, the Kaplan-Meier survival curves were processed and compared using Log-Rank tests and Harrell-C concordance index.ResultsThe 5-year bPFS for the Candiolo risk-classes range between 98 and 38%, and the 5-year cPFS between 98 and 50% for very-low and very-high-risk, respectively. The Candiolo nomogram is highly significant for the stratification of both bPFS and cPFS (P < 0.0001), as well as the D’Amico classification (P = 0.004 and P = 0.001, respectively). For the Candiolo nomogram, the C indexes for bPFS and cPFS are 75 and 80%, respectively, while for D’Amico classification they are 64 and 69%, respectively. The Candiolo nomogram can identify a greater number of patients with low and very-low-risk prostate cancer (61% versus 21% according to D’Amico) and it better picks out patients with high and very-high-risk of recurrence, equal to only 15% of the total cases but subject to 48% (27/56) of biochemical relapses and 63% (19/30) of clinical progressions.Conclusionsthe external validation of the Candiolo nomogram was overall successful with C indexes approximately 10% higher than the D’Amico control classification for bPFS and cPFS. Therefore, its clinical use is justified in prostate cancer patients before radical Radiotherapy.Trial registration Retrospectively registered.

The Effect of Positive Biopsy Cores on the Prognosis of Patients with Intermediate Risk Prostate Cancer Treated with Cs-131 Prostate Brachytherapy

Patients diagnosed with intermediate risk (IR) prostate cancer (PC) have a widely variable prognosis and treatment options. Favorable intermediate risk (FIR) is defined as having only 1 IR factor (Gleason Grade (GG) 2-3, PSA>10 but <20, T2b-c) and no GG3. Unfavorable intermediate risk (UIR) patients have either GG3 disease or >1 IR factors. The amount of disease, as defined by % of positive biopsy cores, has also been proposed as a risk factor, but this to be better defined. In addition, it is unknown whether only the highest GG should be considered or if any core with PC should be counted in the total number of positive cores. We report on our cohort of 299 IR PC patients who were treated with Cs-131 prostate brachytherapy (PB), all of whom have at least 24 mo of follow up and median follow up of 70.6 mo. In general, FIR patients were treated with PB alone (115 Gy) and UIR patients were treated with EBRT (45 Gy) + PB (85 Gy). We stratified patients based on their % of positive cores to determine the effect of this on outcome. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical progression free survival (bPFS), which was defined as the absence of a serum PSA that rose at least 2 ng/mL greater than post-treatment nadir PSA. 164 patients were FIR and 135 were UIR. 203 had GG2 histology and 96 had GG3. Patients with GG2 trended toward a higher 5-year bPFS of 95.9% (SE 0.015) when compared to GG3 patients who had a 5-year bPFS of 87.3% (SE 0.041) (p = 0.065). Looking at the cohort of patients with GG2 disease, patients with <50% cores positive for GG2 disease (n = 178) had a 5-year bPFS of 95.3%, with 81.9% of those patients receiving PB alone. Patients with > 50% cores positive for GG2 disease (n = 25), had a 5-year bPFS of 100% with 80% of those patients receiving EBRT + PB. In the group with GG3, patients with > 50% cores positive for GG3 trended toward a worse outcome (5-year bPFS of 82.1%) compared to those with <50% positive (5-year bPFS = 89.4%) (p = 0.095). In patients treated with Cs-131 PB, those with GG2 disease have an excellent prognosis, regardless of % of biopsy cores positive for PC. Patients with GG3 and < 50% of cores positive also have an excellent prognosis, while patients with GG3 and >50% of cores positive seem to have a worse prognosis and likely would benefit from more aggressive treatment, such as trimodality therapy.

External Beam Radiation Therapy (EBRT) and High-Dose-Rate (HDR) Brachytherapy for Intermediate and High-Risk Prostate Cancer: The Impact of EBRT Volume

Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site. A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive. Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed. A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity.

Salvage radiation therapy following radical prostatectomy in Stockholm County in 2008–2016

This is a large single-institution report including 714 consecutive prostate cancer patients who received salvage radiation therapy (SRT) between 2008 and 2016 in Stockholm, Sweden. The aim of the study was to determine the PSA outcomes of salvage radiotherapy in a cohort of prostate cancer patients after radical prostatectomy (RP). All patients have been treated with 70 Gy during a 7-week period. STHLM-0 database was the source of all PSA test results in Stockholm. During a median follow-up of 48 months after radiotherapy treatment, 49% of patients had no signs of biochemical failure (BcF), 13% experienced BcF, and 38% never reached PSA nadir and subsequently progressed after SRT. Five-year biochemical free survival (bPFS) was 47%. Low PSA at SRT start as well as low preoperative Gleason score and T-stage were independently associated with favorable 5-year biochemical progression-free survival. Patients who started SRT at PSA < 0.28 ng/ml had the best 5-year bPFS of 58%. Median pre-SRT PSA was 0.28 ng/l (0.2–0.45) indicating the good standard of salvage radiotherapy process from patient referral to start of radiotherapy in Stockholm County.

High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes.

To examine the long-term outcomes of high dose rate brachytherapy boost (HDR-BT) combined with external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer patients. Data from 95 patients who underwent combined EBRT (50.4Gy) and HDR-BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method. Regression analysis was conducted to identify important predictors of outcomes. A total of 24 patients received an initial HDR-BT dose of 18Gy in three fractions, with the remaining 71 patients receiving 16Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow-up was 58months. The 5-year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P>0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%. The combined HDR-BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre-emptive TURP and/or HS insertion.

Salvage radiotherapy after radical prostatectomy: Long-term results of urinary incontinence, toxicity and treatment outcomes

PurposeFor patients with local recurrent disease after radical prostatectomy (35–54%) salvage radiotherapy (SRT) is the treatment of choice. In the post prostatectomy setting, SRT may impose risk at increased toxicity. As data on long-term toxicity, especially on urinary incontinence, are scarce, we report on the long-term treatment outcomes, toxicity and urinary incontinence rates after SRT. Materials and methodsPatients with biochemically recurrent prostate cancer after radical prostatectomy, who were treated with SRT (3D-CRT) at our institution between 1998 and 2012, were included in this retrospective cohort analysis. Primary endpoint was urinary incontinence rate. Secondary endpoints were acute and late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicity rates, biochemical progression-free survival (bPFS), distant metastasis-free survival (DMFS), disease specific survival (DSS), and overall survival (OS). Results244 patients were included. Median follow-up after SRT was 50 months (range: 4–187 months). Before start of SRT 69.7% of patients were continent for urine. After SRT de novo urinary incontinence complaints (grade ≥ 1) occurred in the respective acute and late phase in 6.1% and 17.6% of patients. Respective acute grade ≥2 GU and GI toxicity was 19.2% and 17.6%. Late grade ≥2 toxicity for GU was 29.9% and for GI was 21.3%, respectively. The respective 5-year bPFS, OS, DSS and DMFS rates were 47.6%, 91.8%, 98.8% and 80.5%. ConclusionsExperience at our institution with SRT demonstrates that this results in good long-term biochemical control. However, toxicity and urinary incontinence rates were high.

Identification of curable high-risk prostate cancer using radical prostatectomy alone: who are the good candidates for undergoing radical prostatectomy among patients with high-risk prostate cancer?

BackgroundCurrently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with high-risk PCa who are treatable by RP alone.MethodsWe retrospectively reviewed data on 315 patients with D’Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors.ResultsAt a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92, p < 0.05) and % positive core (≥ 30%, HR 2.85, p < 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03; p < 0.0001).ConclusionThe risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%).

Five-year effectiveness of low-dose-rate brachytherapy: comparisons with nomogram predictions in patients with non-metastatic prostate cancer presenting significant control of intra- and periprostatic disease.

PurposeTo assess the effectiveness of low-dose-rate (LDR) brachytherapy in patients with localized prostate cancer and to compare the outcome with predictions from Kattan and Partin nomograms at 60 months after seed implantation.Material and methodsOne thousand, one hundred and eighty-seven patients with localized prostate cancer at low-, intermediate-, or high-risk of progression received LDR brachytherapy using iodine-125 seeds with curative intent, applied as monotherapy or in combination with external beam radiation therapy (EBRT), and/or androgen deprivation therapy (ADT). At 60 months after seed implantation, data of 1,064 patients (1,058 alive + 6 who died of prostate cancer) were analyzed for biochemical progression-free survival (bPFS) based on prostate-specific antigen (PSA) levels using the Phoenix definition. Five-year bPFS probabilities were determined for various risk group classifications (d’Amico, Mt. Sinai, MSKCC/Seattle, NCCN). Outcomes were also compared to patient-individualized nomogram predictions of 5-year bPFS (Kattan 2002) and probability of organ-confined disease (Kattan 2002, Partin 2007).ResultsOverall, 93.3% (993/1,064) of the patients were free of biochemical progression within 5 years, while the average 5-year bPFS probability according to the Kattan nomogram was significantly lower (85%, p < 0.001). Outcomes were significantly better than Kattan nomogram predictions in the subgroup of patients with monotherapy as well as in patients additionally treated with EBRT. Comparison of the overall outcome with nomogram predictions for organ-confined disease (Kattan nomogram: 50%; Partin nomogram: 65%) revealed a significant probability of LDR brachytherapy to destroy periprostatic tumor spread (p < 0.001) in all risk group constellations, even in high-risk patients.ConclusionsThe results indicate high effectiveness of LDR brachytherapy in all risk groups, significantly better than predicted with the Kattan nomogram in most subgroups. The significant superiority of LDR brachytherapy compared to nomogram predictions of organ-confined disease suggests that LDR brachytherapy effectively controls both intra- and periprostatic disease.

Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer

Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2ng/mL. A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6months (LRC), 59.2months (IRC), 74.9months (LRB), and 59.8months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001).The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was-35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset.