Pretreatment Prostate-specific Antigen Level Research Articles

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Circulating tumor DNA and homologous recombination deficiency in bone-predominant mCRPC prior to radium-223 therapy.

203 Background: Radium-223 (Ra-223) is a bone-seeking alpha emitter that induces double-stranded DNA breaks, and the homologous recombination (HR) pathway is critical for repairing these breaks. While prior studies suggested that metastatic castrate-resistant prostate cancers (mCRPC) patients (pts) with HR-deficient (HRD+) tumors may be more likely to benefit from Ra-223, obtaining tissue for next generation sequencing to identify HRD+ is challenging in pts with bone-predominant disease. We hypothesized that circulating tumor DNA (ctDNA) would allow for broader identification of HRD+ to assess association with clinical outcomes in a real-world cohort. Methods: We identified 135 mCRPC pts treated with Ra-223 at our institution between 2013 and 2021. Pts who initiated another anti-tumor therapy within 60 days of Ra-223 treatment were excluded; pts continuing hormonal agents initiated &gt;60 days prior were included. ctDNA isolated from pre-treatment plasma underwent ultra-low-pass whole genome sequencing to estimate tumor fraction (TF). Additionally, targeted panel sequencing using an institutional prostate cancer-specific panel of 319 genes with duplex sequencing (utilizing unique molecular identifiers) for error suppression was used to identify germline or somatic deleterious alterations in HR pathway genes. The primary outcome was association between HRD status and completion of fewer than 6 cycles (as a proxy for early clinical progression), assessed using logistic regression. Results: The median age was 61 (IQR, 56-67) years, median pretreatment prostate-specific antigen (PSA) level was 26.2 (IQR, 8.1-84.1) ng/mL, and median TF was 4% (IQR, 3-6%). 97% of pts (n=131) previously received a novel antiandrogen, and 63% (n=85) received prior taxane. 17% (n=23) were HRD+, and 59% (n=80) completed 6 cycles of Ra-223. On multivariable analysis, HRD+ was associated with decreased likelihood of completing 6 cycles compared to HRD- (adjusted odds ratio [AOR] 0.16, 95% confidence interval [CI] 0.05-0.48, P=0.001). 22% (n=5) of HRD+ pts completed 6 cycles compared to 67% (n=75) of HRD- pts. Additional factors associated with decreased likelihood of completing 6 cycles included a higher pretreatment TF (AOR 0.69, 95% CI, 0.48-0.97, P=0.034) and prior taxane use (AOR 0.41, 95% CI, 0.18-0.91, P=0.028), but not pretreatment PSA ( P=0.574). Conclusions: Targeted panel sequencing with error suppression from ctDNA identified HRD+ in mCRPC pts with bone-predominant disease and low median TF at a similar frequency as reported from tissue. In our cohort, HRD+ was prognostic of early clinical progression with Ra-223. Further work is in progress to understand the association of other ctDNA-derived features, including assessment of genomic signatures and transcriptional binding sites, in the setting of Ra-223 therapy. DF/HCC IRB protocol 18-135.

Role of baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting survival outcomes of metastatic castration-resistant prostate cancer patients receiving first-line treatment.

We aimed to evaluate whether baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters could be used as predictive biomarkers for survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line treatment. This retrospective study included 54 mCRPC patients, who underwent baseline 68Ga-PSMA PET/CT imaging within 1month before starting first-line treatment. Pre-treatment prostate-specific antigen (PSA) levels and treatments were recorded. SUVmax, SUVmean, whole-body PSMA-derived tumor volume (wbPSMA-TV), and whole-body total lesion PSMA (wbTL-PSMA) were calculated for all patients. PSA response was defined as a decline of ≥ 50% from pre-treatment value at 12weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC. Docetaxel and abiraterone/enzalutamide were administered to 32 and 22 patients in the first-line setting, respectively. wbPSMA-TV (rho = 0.582, p = 0.004) and wbTL-PSMA (rho = 0.564, p = 0.007) showed moderate positive correlations with PSA levels. Older age (p = 0.02), higher wbPSMA-TV (p = 0.007), higher PSA (p = 0.01), higher number of bone metastases (p = 0.02), and lack of PSA response (p = 0.03) were significantly associated with an increased risk of mortality. Multivariate analysis determined wbPSMA-TV (HR: 1.003, 95% CI 1.001-1.004, p = 0.001) and PSA response (HR: 2.241, 95% CI 1.189-4.222, p = 0.01) as independent predictors of OS. The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC.

Robot-assisted radical prostatectomy in the treatment of patients with clinically high-risk localized and locally advanced prostate cancer: single surgeons functional and oncologic outcomes

BackgroundOptimal treatment approaches for high-risk localized and locally advanced prostate cancer remain controversial and there are currently no standard treatments. These patients with high-risk localized and locally advanced prostate cancer are usually offered radiotherapy in combination with hormonal therapy. We report functional and oncologic outcomes of patients who underwent primary robot-assisted radical prostatectomy (RARP) and assess the role of RARP in patients with high-risk localized and locally advanced prostate cancer.MethodsThis study included 188 patients with high-risk localized (clinical stage T2c or a pretreatment prostate-specific antigen level > 20 ng/mL or a biopsy Gleason score ≥ 8) and/or locally advanced (any PSA, cT3-4 or cN+) prostate cancer who underwent RARP between July 2013 and May 2020. Functional outcomes including postoperative continence and potency were assessed at 1, 3, 6, and 12 months after RARP. Oncologic outcomes comprised positive surgical margins (PSMs), biochemical recurrence (BCR), BCR-free survival, and clinical recurrence (CR)-free survival rates at 1 and 3 years.ResultsThe median operative time was 185 (interquartile range [IQR] 130–260) minutes. Based on postoperative pathology, the rates of PSMs in the entire cohort and in those with stage pT2 disease were 26.6% and 8.5%, respectively. The continence and potency rates at 12 months were 88.3% and 56.4%, respectively. The BCR rate was 22.3%, and the median time to BCR was 10.5 (IQR 3.5–26.9) months. The 1- and 3-year BCR-free survival rates were 87.6% and 78.7%, respectively, and the 1- and 3-year CR-free survival rates were 97.5% and 90.8%, respectively.ConclusionsMost patients with clinically high-risk localized and locally advanced prostate cancer treated with primary RARP remained BCR-free and CR-free during the 1- and 3-year follow-up, demonstrating the good functional outcomes with RARP. RARP was a safe and feasible minimally invasive surgical alternative to radiotherapy or hormonal therapy in select patients with high-risk localized and locally advanced prostate cancer. These results should be validated to assure the reproducibility of measurements in prospective randomized-controlled studies on primary RARP.

The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer

Prostate-specific antigen (PSA) secretion is a testosterone (T) dependent process. Published data suggest that a low T level is an independent predictor of higher-grade prostate cancer (PC). To evaluate the relationship between T and PSA in patients with PC. All men diagnosed with PC with a recorded pre-treatment total T level measurement were included in this analysis. We analyzed demographic, clinical, and pathological data. Patients were stratified according to pretreatment PSA levels: <2 ng/mL, 2-4 ng/mL, >4 ng/mL. Low T was defined as total T < 10.4 nmol/L (300 ng/dL), very low T < 6.9 nmol/L (200 ng/dL). T levels by PSA groups according to the PC pathology. In this retrospective study, mean patient age was 61 years among 646 men. The distribution by PSA group was: 8% (<2), 17% (2-4), and 76% (>4). The mean T level across the entire cohort was 13 nmol/L (374 ng/dL). Overall, 30% had a T level < 10.4 nmol/L (300 ng/dL). The mean total T level by PSA group was: <2 ng/mL, 7 nmol/L (206 ng/dL); 2-4 ng/mL, 13 nmol/L (362 ng/dL); >4 ng/mL, 14 nmol/L (393 ng/dL), P < .001. PSA <4 ng/mL was a significant predictor of low T in men with PC GS ≥8. PSA <2 ng/mL was a significant predictor of very low T independent of the PC pathology. These findings suggest that clinicians should consider measuring T levels when a patient diagnosed with PC GS ≥8 and PSA level <4 ng/mL, and for each patient with PSA level <2 ng/mL independent of the PC pathology. Our study has several strengths including (i) inclusion of a large population of men, (ii) use of a database which is audited and reviewed for accuracy annually, and (iii) use of an accurate T assay (LCMS). Nonetheless, there are limitations: (i) the subjects of the study are from a single institution, and (ii) we did not measure free T levels. In men with PC with GS ≥8, PSA level <4 ng/mL predicts low T. PSA <2 ng/mL predicts very low T independent of the PC pathology. Flores JM, Bernie HL, Miranda E, et al. The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer. J Sex Med 2022;19:471-478.

Predictive factors of survival outcomes in first-line therapy for metastatic castration-resistant prostate cancer.

To investigate predictive factors of survival of metastatic castration-resistant prostate cancer patients undergoing first-line treatment with androgen receptor pathway inhibitors or docetaxel. Japanese patients with metastatic castration-resistant prostate cancer treated with androgen receptor pathway inhibitor or docetaxel between 2008 and 2018 were included. The differential impact of various clinicopathological factors on the outcome, including progression-free survival and overall survival, was compared between treatment with androgen receptor pathway inhibitor and docetaxel. Of 254 patients with metastatic castration-resistant prostate cancer, 119 (46.9%) and 135 (53.2%) were treated with androgen receptor pathway inhibitor and docetaxel, respectively. The multivariate analysis showed that androgen receptor pathway inhibitor was an independent prognostic factor for better progression-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, P = 0.016) and overall survival (hazard ratio 0.61, 95% confidence interval 0.41-0.93, P = 0.021), compared with docetaxel. Pretreatment prostate-specific antigen levels and time to castration-resistant prostate cancer were differentially associated with progression-free survival and overall survival between androgen receptor pathway inhibitor or docetaxel. In patients who presented <6 months to castration-resistant prostate cancer, progression-free survival was shorter in those treated with androgen receptor pathway inhibitor (median 1.1 months, 95% confidence interval 0.2-2.8 months) compared with those who received docetaxel (median 5.0 months, 95% confidence interval 1.8-6.7 months; P = 0.014). First-line therapy with androgen receptor pathway inhibitor is associated with a better prognosis when compared with docetaxel, even after adjustment for prognostic factors. However, a shorter time to castration-resistant prostate cancer is associated with better progression-free survival for patients receiving docetaxel, suggesting that docetaxel is the preferred option for patients with a shorter time to castration-resistant prostate cancer.

Prostate-specific antigen dynamics after neoadjuvant androgen-deprivation therapy and carbon ion radiotherapy for prostate cancer.

This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria. The median patient age was 68 (range, 48-81) years. The median follow-up duration was 33 (range, 20-48) months. The clinical T stage was T1c, T2a, and T2b in 27, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33-19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2-117) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6-30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15-33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age and lower T stage were significant predictors of PSA bounce. Younger age was a significant predictor of PSA failure. In this study, we identified the significant predictors of the occurrence of PSA bounce and failure. Further follow-up is needed to reveal the clinical significance of PSA dynamics.

Serum total prostate-specific antigen (tPSA): correlation with diagnosis and grading of prostate cancer in core needle biopsy.

Aim To investigate the impact of pre-treatment serum total prostate-specific antigen (PSA) level on prevalence of prostate carcinoma detection in prostate core needle biopsy, and its correlation with established prognostic factors. Methods Prostate needle biopsy samples of 115 patients with available pre-treatment serum total PSA (tPSA) level were analysed. For all cases where morphology alone was insufficient, immunohistochemistry was performed using p63, CKHMW and AMACR antibody panel in order to confirm or exclude the existence of prostate carcinoma. Results Statistically significant positive correlation between serum total PSA values and prevalence of finding prostate carcinoma in needle biopsy specimens was found (p=0.011), as well as in the case when the patients were classified into groups according to tPSA levels (p=0.028). Serum total PSA values and levels (level groups) showed significant positive correlation with Gleason score (p=0.029 and p=0.036, respectively) and Grade Group of prostate carcinomas (p=0.044 and p=0.046, respectively). Sensitivity of the screening test by using 4 ng/mL as cut off value for tPSA was 94.12% (CI: 80.32-99.28%), specificity 8.64% (CI: 3.55-17.00%), positive predictive value 30.19% (CI: 21.65-39.87%) and negative predictive value 77.78% (CI: 39.99-97.19%). Conclusion The increase of serum tPSA value increases the likelihood of finding prostate cancer on needle biopsy specimens. Due to such findings and its positive correlation with a grade of prostate cancer, our study indicates that tPSA can still be considered as a useful tool both in detecting and predicting aggressiveness of prostate cancer.

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials

To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer. This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs>0.1ng/mL) groupings, and clinical outcomes. The median follow-up for surviving patients was 9.4years. The median post-neoAS, pre-RT PSA level was 0.3ng/mL, with 32% of patients having levels ≤0.1ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and>0.1ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P<.0001); local failure (HR, 2.51; P<.0001); distant metastases (HR, 1.73; P=.0006); cause-specific mortality (HR, 2.36; P<.0001); and all-cause mortality (HR, 1.24; P=.005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P<.0001); local failure (HR, 2.33; P<.0001); and cause-specific mortality (HR, 1.75; P=.03). Patients with a PSA level >0.1ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

Definitive external-beam radiotherapy versus radical prostatectomy in clinically localized high-risk prostate cancer: a retrospective study

BackgroundOptimal treatment of high-risk prostate cancer remains controversial. We aimed to compare treatment outcomes of prostate cancer patients treated with definitive external-beam radiotherapy (ExRT) or radical prostatectomy (RP).MethodsThe records of 120 high-risk clinical stage T2b-T4 N0 M0 prostate cancer patients treated with definitive ExRT or RP were reviewed. Patients with pretreatment prostate-specific antigen (PSA) levels ≥20 ng/mL or clinical ≥T3 stage or Gleason score (GS) ≥8 were included in the study. Biochemical failure free survival (BFFS), distant metastasis free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. Cox regression analysis was performed to determine predictors of BF.ResultsSeventy-two patients received definitive ExRT with androgen-deprivation therapy in 95.8% and 48 patients underwent RP with pelvic lymph node dissection. Mean age (67.7 ± 6.6 vs 64.5 ± 7.6 year, p = 0.017) and the rate of patients with PSA levels ≥20 ng/mL (69.4% vs 47.9%, p = 0.022) were higher in the definitive ExRT group than the RP group. Distributions of GS and clinical T stage were similar. Mean follow-up was 60.2 ± 30.3 months in the definitive ExRT group and 41.3 ± 21.5 months in the RP group (p < 0.001). Twenty-five % of the RP group received adjuvant ExRT and 41.7% received salvage ExRT. Biochemical failure was significantly higher (52.1% vs 21.4%, p < 0.001) and the mean BFFS was significantly lesser (34.4 ± 3.9 vs 97.8 ± 5.9 months, p < 0.001) in the RP group than the definitive ExRT group. However, DMFS, CSS and OS were similar in both groups. In multivariate analysis, being in the RP group significantly increased the risk of BF (p < 0.001). Furthermore, not receiving pelvic lymphatic irradiation in the definitive ExRT group (p = 0.048) and having positive surgical margin in the RP group (p = 0.050) increased the risk of BF.ConclusionsBF was significantly higher and the mean BFFS was significantly lesser in high-risk prostate cancer patients undergoing RP than definitive ExRT while DMFS, CSS and OS were similar in both treatment groups.

Usefulness of combined androgen blockade therapy with gonadotropin-releasing hormone antagonist for bone metastatic prostate cancer with pretreatment prostate-specific antigen level \u2265 50 ng/mL

BackgroundThis study was performed to examine the usefulness of combined androgen blockade (CAB) therapy with a gonadotropin-releasing hormone (GnRH) antagonist (CAB-antagonist therapy), instead of CAB therapy with GnRH agonist (CAB-agonist therapy) against very high-risk prostate cancer (Pca).MethodsWe retrospectively studied 84 Pca patients with pretreatment prostate-specific antigen (PSA) level ≥ 50 ng/mL, who were pathologically diagnosed between January 2007 and December 2016. GnRH antagonist was administered to 34 patients and GnRH agonist was administered to 50 patients. All patients received concurrent antiandrogen treatment.The primary end point was PSA progression-free survival (PSA-PFS).ResultsPSA-PFS was significantly longer for the CAB-antagonist group compared to the CAB-agonist group (log-rank test, P < 0.01) in Pca patients with more than six bone metastases (the extent of disease [EOD] grade 2–4). On multivariate analysis, CAB-antagonist therapy was shown to be a possible prognostic factor for PSA-PFS (adjusted hazard ratio: 0.41, 95% confidence interval: 0.16–0.90, P = 0.03).ConclusionsCAB-antagonist therapy may be a useful option in bone metastatic Pca patients with EOD grade 2–4.

Long-term Results of External Beam Radiotherapy for Prostate Cancer with Prostate-specific Antigen of More Than 50 ng/ml and Without Evidence of Lymph Node or Distant Metastasis.

To evaluate long-term treatment outcomes of external beam radiotherapy for prostate cancer with a pretreatment prostate-specific antigen (PSA) level of more than 50 ng/ml and without evidence of lymph node or distant metastasis. Definitive radiotherapy of 66 Gy or 72 Gy in combination with androgen deprivation therapy (ADT) was performed. PSA relapse-free survival (PRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were evaluated. The impact of prognostic factors on PRFS, DMFS, CSS, and OS was analyzed in univariate and multivariate analyses. One hundred twenty patients with a median follow-up period of 92.6 months were analyzed in this study. The median duration of ADT was 11.0 months. The 5- and 8-year PRFS rates in all patients were 65.1% and 48.5%, respectively. The 8-year DMFS, CSS, and OS rates in all patients were 84.0%, 93.4%, and 81.6%, respectively. Both in univariate and multivariate analyses, Gleason score (GS) and radiotherapy dose were significant prognostic factors (p=0.015 and 0.001). There was no significant difference between each prognostic factor in DMFS, CSS, and OS. We might have indicated the significance of definitive radiotherapy even for prostate cancer with PSA of more than 50 ng/ml and without evidence of metastasis.

Predictive value of epithelial-mesenchymal-transition (EMT) signature and PARP-1 in prostate cancer radioresistance.

Epithelial-mesenchymal-transition (EMT) has been previously identified as a contributor to prostate cancer progression to metastasis and therapeutic resistance to antiandrogens and radiotherapy. In this study we conducted a retrospective analysis to investigate the significance of radiation-induced EMT and consequential changes to the tumor microenvironment in biochemical recurrence and response to radiotherapy in prostate cancer patients. Expression profiling and localization for EMT effectors, E-Cadherin, N-Cadherin, β-catenin and Vimentin was assessed in human prostate tumor specimens pre- and post-radiotherapy and correlated with biochemical recurrence. In addition, immunoreactivity of the DNA repair enzyme, polymerase (PARP-1) and the cytoskeletal-remodeling regulator, cofilin was evaluated in prostate tumor specimens pre- and post-radiotherapy and correlated with pre-treatment prostate-specific antigen levels (PSA). Our findings identified that characteristic changes associated with the EMT phenotype and its reversal to mesenchymal-epithelial-transition (MET) within the tumor microenvironment correlate with biochemical recurrence and resistance to radiotherapy among prostate cancer patients. Moreover, elevated PARP-1 expression among the tumor cells undergoing EMT implicates that DNA repair mechanisms may potentially reverse the cytotoxic effects of radiotherapy-induced DNA breaks. Our results suggest that EMT programming effectors, integrated with the actin cytoskeleton regulator cofilin and mesenchymal PARP-1 expression profile provide a signature of potential predictive significance of therapeutic response to radiotherapy in a subset of prostate cancer patients.

An evaluation of irreversible electroporation thresholds in human prostate cancer and potential correlations to physiological measurements.

Irreversible electroporation (IRE) is an emerging cancer treatment that utilizes non-thermal electric pulses for tumor ablation. The pulses are delivered through minimally invasive needle electrodes inserted into the target tissue and lead to cell death through the creation of nanoscale membrane defects. IRE has been shown to be safe and effective when performed on tumors in the brain, liver, kidneys, pancreas, and prostate that are located near critical blood vessels and nerves. Accurate treatment planning and prediction of the ablation volume require a priori knowledge of the tissue-specific electric field threshold for cell death. This study addresses the challenge of defining an electric field threshold for human prostate cancer tissue. Three-dimensional reconstructions of the ablation volumes were created from one week post-treatment magnetic resonance imaging (MRIs) of ten patients who completed a clinical trial. The ablation volumes were incorporated into a finite element modeling software that was used to simulate patient-specific treatments, and the electric field threshold was calculated by matching the ablation volume to the field contour encompassing the equivalent volume. Solutions were obtained for static tissue electrical properties and dynamic properties that accounted for electroporation. According to the dynamic model, the electric field threshold was 506 ± 66 V/cm. Additionally, a potentially strong correlation (r = −0.624) was discovered between the electric field threshold and pre-treatment prostate-specific antigen levels, which needs to be validated in higher enrollment studies. Taken together, these findings can be used to guide the development of future IRE protocols.

68Ga-PSMA Ligand PET/CT-based Radiotherapy for Lymph Node Relapse of Prostate Cancer After Primary Therapy Delays Initiation of Systemic Therapy

To evaluate 68Ga-PSMA ligand positron-emission tomography-computed tomography (PET/CT)-based radiotherapy for lymph node metastases of prostate cancer after primary therapy. Twenty-three patients received radiotherapy for PSMA ligand-positive lymph node metastases. The median follow-up time was 12.4 (range=6.0-28.5) months. The median pre-treatment prostate-specific antigen (PSA) decreased from 2.75 (range=0.52-8.92) ng/ml to a nadir of 1.37 (range=0.11-8.00) ng/ml (p=0.001) following radiotherapy. Except for one patient (4.4%), PSA level decreased in 22 patients (95.6%). The biochemical failure-free survival and time to initiation of systemic therapy at the median follow-up were 95.6% and 100%, respectively. Three patients (12.9%) presented with recurrent disease outside the initial radiation field. No grade III acute toxicities or late grade II toxicities were observed. 68Ga-PSMA ligand PET/CT-based radiotherapy is a promising local treatment option for isolated lymph node metastases of prostate cancer.

A Prospective Trial of Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-term Outcomes Compared With Standard Image Guided IMRT

This report describes the long-term outcomes of a prospective trial of intensity modulated radiation therapy (IMRT), integrating a 111In capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Seventy-one patients with T1N0M0 to T4N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning.The entire prostate received 75.6Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82Gy as an SIB. Patients with intermediate- and high-risk disease also received 6months and 12months of adjuvant hormonal therapy, respectively. The study enrolled 31 low-, 30 intermediate-, and 10 high-risk patients. The median follow-up was 120months (range, 24-150months). The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB and followed up for a median of 91months (range, 6-138months). The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB (P=.02). The cohort that received an SIB did not have increased toxicity. The described IMRT strategy, integrating multiple imaging modalities to administer 75.6Gy to the entire prostate with a boost dose of 82Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy

To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage≤T2a, prostate-specific antigen level ≤15ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50cm3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192Ir to a dose of 19Gy prescribed to the prostate, with no additional margin applied. Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9years (range 0.3-5.2). The median age was 61.4years. The median gland volume at treatment was 34.8cm3. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.

Hypofractionated image guided radiation therapy followed by prostate seed implant boost for men with newly diagnosed intermediate and high risk adenocarcinoma of the prostate: Preliminary results of a phase 2 prospective study

PurposeA phase 2 protocol was designed and implemented to assess the toxicity and efficacy of hypofractionated image guided intensity modulated radiation therapy (IG-IMRT) combined with low-dose rate 103Pd prostate seed implant for treatment of localized intermediate- and high-risk adenocarcinoma of the prostate. Methods and materialsThis is a report of an interim analysis on 24 patients enrolled on an institutional review board–approved phase 2 single-institution study of patients with intermediate- and high-risk adenocarcinoma of the prostate. The median pretreatment prostate-specific antigen level was 8.15 ng/mL. The median Gleason score was 4 + 3 = 7 (range, 3 + 4 = 7 - 4 + 4 = 8), and the median T stage was T2a. Of the 24 patients, 4 (17%) were high-risk patients as defined by the National Comprehensive Cancer Network criteria, version 2016. The treatment consisted of 2465 cGy in 493 cGy/fraction of IG-IMRT to the prostate and seminal vesicles. This was followed by a 103Pd transperineal prostate implant boost (prescribed dose to 90% of the prostate volume of 100 Gy) using intraoperative planning. Five patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy. ResultsThe median follow-up was 18 months (range, 1-42 months). The median nadir prostate-specific antigen was 0.5 ng/mL and time to nadir was 16 months. There was 1 biochemical failure associated with distant metastatic disease without local failure. Toxicity (acute or late) higher than grade 3 was not observed. There was a single instance of late grade 3 genitourinary toxicity secondary to hematuria 2 years and 7 months after radiation treatment. There were no other grade 3 gastrointestinal or genitourinary toxicities. ConclusionsEarly results on the toxicity and efficacy of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy boost are favorable. Longer follow-up is needed to confirm safety and effectiveness.

High Absolute Monocyte Count Predicts Poor Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Treated with Docetaxel Chemotherapy.

The association of peripheral monocyte count and prostate cancer progression is not well characterized. Our aim was to investigate the prognostic value of absolute monocyte count (AMC), which is thought to modulate immune response in the tumor microenvironment, in castration-resistant prostate cancer (CRPC) patients treated with docetaxel chemotherapy. We retrospectively reviewed the medical records of 214 CRPC patients who received docetaxel therapy and were used as the training and validation set. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4weeks. Clinicopathological factors and laboratory data were collected to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). In the training set, the median age was 73.0years, and the median prostate-specific antigen (PSA) value was 31.7 ng/ml at initial treatment. The median OS and PFS were 23.0 months (range 1.20-84.0) and 11.2 months (range 3.6-78.0), respectively. According to multivariable Cox regression analysis, AMC ≥400/uL, PSA level ≥20ng/ml, and Hb <10mg/dL were associated with increased risk of PSA progression [hazard ratio (HR) 2.06, p=0.005; HR 2.39, p=0.002; and HR2.38, p=0.024, respectively]. Moreover, multivariate analysis for OS indicated that AMC ≥400/uL, pretreatment PSA level ≥20ng/ml, presence of visceral metastasis, and alkaline phosphatase ≥284U/L were independent prognostic factors for shortened OS (HR2.07, p=0.004; HR2.18, p=0.007; HR 2.11, p=0.011; and HR 1.67, p=0.048, respectively). According to the validation set, high AMC remained an independent prognostic factor for PFS and OS (HR2.26, p=0.001; and HR3.10, p<0.001, respectively). Elevated monocyte counts were associated with aggressive tumor features and poor survival outcomes of patients with CRPC treated with docetaxel chemotherapy.

Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR = 0.197, AUC = 0.582).