Biochemical Progression Research Articles

Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer (EXTEND): A Multicenter, Randomized Phase II Trial

<h3>Purpose/Objective(s)</h3> There has been increased utilization of metastasis directed therapy (MDT) for oligometastatic prostate cancer. Despite data demonstrating the benefit of upfront hormone therapy (HT) and synergy between radiation and HT, there exists no randomized trials testing their combination. As it is accepted by most clinicians and men with prostate cancer that time off HT holds intrinsic value, we evaluated whether the addition of metastasis directed therapy (MDT) to intermittent HT in men with oligometastatic prostate cancer facilities time off HT by improving PFS and eugonad PFS. <h3>Materials/Methods</h3> EXTEND (NCT03599765) is a phase II randomized basket trial for multiple solid tumors testing whether the addition of MDT improves PFS. The primary endpoint was pre-specified to be independently assessed and reported for the prostate intermittent HT basket at 41 events. Men with ≤5 metastases were randomized after ≥2 months of HT to continuing HT with or without MDT. HT consisted of a luteinizing hormone-releasing hormone agonist/antagonist with or without a 2^nd generation androgen-receptor targeting agent (SART). The primary endpoint was progression, defined as death or radiographic, clinical, or biochemical progression. A planned HT break occurred 6 months after enrollment, after which HT was withheld until progression. The study was designed to have 80% power to detect an improvement in median PFS from 18 to 36 months, with a type I error of 0.1. Exploratory analysis included flow cytometry and TCR sequencing from peripheral blood at baseline and 3 months follow up. <h3>Results</h3> Between Sept 2018 to Nov 2020, 87 men were randomized, 43 combined therapy and 44 to HT-only. Arms were well balanced. At a median follow-up of 22.1 months (range 13.0 to 39.3 months), 41 events were observed. PFS was improved by the receipt of MDT (median not reached vs 15.8 months for HT-only, P<0.001; HR=0.25 [95% CI, 0.12 to 0.55]). Among secondary endpoints, time from eugonad testosterone levels (>150 ng/dL) to progression was improved by MDT (median not reached vs 6.1 months, P=0.03), as was time to appearance of new lesions (2-year rate 33% vs 41%, P=0.04). Three grade 3 toxicities were observed in each arm. Subgroup analysis identified PFS improvement with MDT in patients who received (HR=0.24 [95% CI, 0.08 to 0.71]) or did not receive a SART (HR=0.36 [95% CI, 0.15 to 0.83]). Flow cytometry and TCR sequencing demonstrated increases in markers of T cell activation, proliferation, and clonal expansion limited to the combined therapy arm. <h3>Conclusion</h3> EXTEND represents the first randomized study to evaluate MDT with HT in oligometastatic prostate cancer and demonstrated improvement in PFS and eugonad PFS. Combination of MDT with intermittent HT may allow for both excellent disease control while facilitating prolonged eugonad testosterone intervals.

Low TLR and PSMA-TV predict biochemical response to abiraterone acetate in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage.

To explore whether 68Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage. The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used. Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68Ga-PSMA-11 PET/CT-derived parameters alone. Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients.

Stereotactic ablative radiotherapy for oligometastatic prostate cancer.

The present study assessed clinical outcomes of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer patients. Between 2017 and 2020, 37 lesions (12 osseous and 25 nodal targets) detected with conventional and/or functional imaging, were treated in 29 patients (pts), in different clinical settings: de novo oligometastatic (2 pts), oligorecurrent castration-sensitive (19 pts), castration-resistant (6 pts) prostate cancers and oligoprogressive disease during systemic therapy (2 pts). SBRT was delivered with volumetric modulated arc therapy up to a total dose of 21 Gy given in 3 fractions for bone and 30 Gy in 5 fractions for nodal metastases. A total of 34% of pts received hormonal therapy. We evaluated biochemical control [prostate serum antigen (PSA) increase < 10%)], progression free-survival (PFS) (time from SBRT to biochemical progression), local control (LC) (time from SBRT to in-field radiologic progression), hormone/systemic therapy-free survival, acute and late toxicities. At 3 months, biochemical response was observed in 20/29 pts (69%). At a median follow-up of 17 months (range 6-33), 8/20 (40%) of the 3-month responders remained free from progression. Two-year PFS and LC were 37% and 70%, respectively. In-field progression occurred in 3/37 (8%) lesions. Hormone/systemic therapy was delayed by an average of 11.6 months (range 3-28). No significant difference in PFS based on the type of lesion or concomitant endocrine therapy was observed and no toxicity > grade 2 was reported. SBRT for oligometastatic prostate cancer offers a good biochemical/local control and tangible delay of hormone/systemic therapy without major toxicities.

Prognostic Utility of Biopsy-Based PTEN and ERG Status on Biochemical Progression and Overall Survival after SBRT for Localized Prostate Cancer

<h3>Purpose/Objective(s)</h3> PTEN deletions and ERG rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies revealed that changes in wild-type PTEN and ERG portend worse clinical outcomes. While early studies were performed on whole-gland samples after radical prostatectomy, subsequent biopsy-based analyses have led to their inclusion in several genomic assays and prostate cancer outcome scores. However, evaluations of therapeutic response to radiotherapy are quite heterogenous. Our objective is to evaluate the impact of biopsy-determined <i>PTEN</i> losses and <i>TMPRSS2-ERG</i> fusion on biochemical disease-free survival (bDFS) in patients who receive SBRT for localized prostate cancer. <h3>Materials/Methods</h3> Patients included in this analysis underwent SBRT for localized prostate cancer and are followed on an institutional prospective quality of life and survival study. For each patient, the single biopsy core with the highest 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 χ<b>²</b> for categorical groupings. bDFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bDFS and OS were evaluated using Cox proportional hazard method. For all analyses, <i>p</i> <0.05 was considered statistically significant. <h3>Results</h3> Ninety-three patients were included in the analysis with a median follow up of 72 months (IQR 52 - 85 months). The 5-year bDFS for all patients was 85.2% with a median bDFS of 98 months. The 5-year OS for all patients was 91.8% with a median OS of 123 months. Differences between ERG and PTEN status groups by age, race, T-stage, NCCN risk group, PSA group, PSA density group, and Charlson Comorbidity Index were not statistically significant. Differences in grade group were statistically significant (<i>p</i> = 0.0329). The estimated 5-year bDFS was 100%, 76.6%, 72.9%, and 63.8% for the ERG+/PTEN, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- groups respectively (<i>p</i> =0.0107). Multivariate analysis (MVA) confirmed an increased likelihood of 5-year biochemical progression with higher NCCN risk group (<i>p</i> <0.0001) and increasing ERG/PTEN mutational burden (<i>p</i><0.0001). <h3>Conclusion</h3> <i>ERG Fusion with PTEN</i> loss is associated with an increased risk of biochemical progression. However, <i>ERG</i> status alone is not predictive of bPFS. Biopsy-based PTEN and ERG assays demonstrate utility in predicting 5-year oncologic outcomes in patients who receive prostate SBRT.

Prognostic and Predictive Performance of a 24-Gene Post-Operative Radiation Therapy Outcomes Score (PORTOS) in a Phase 3 Randomized Trial of Dose-Intensified Salvage Radiotherapy after Radical Prostatectomy (SAKK 09/10)

<h3>Purpose/Objective(s)</h3> The SAKK 09/10 phase 3 trial showed that dose-intensified salvage radiotherapy (SRT) was not superior to conventional dose SRT for biochemically recurrent prostate cancer (PCa) after radical prostatectomy (RP). We previously reported on the validation of the 22-gene genomic classifier as prognostic in this trial but did not observe an interaction with RT dose. Herein, we examine the PORTOS classifier, an expression signature of 24 DNA damage repair and immune pathway genes, previously shown to predict benefit from postoperative radiotherapy, to test its predictive ability to SRT dose. <h3>Materials/Methods</h3> The SAKK 09/10 trial (NCT01272050) was a multicenter, randomized phase 3 trial that included PCa patients with biochemical progression after RP (PSA > 0.1 to 2 ng/mL at randomization). Patients were randomized to 64Gy vs 70Gy to the prostate bed. No patients received concurrent androgen suppression or pelvic nodal radiotherapy. After central review, the highest-grade tumors were profiled using the Decipher whole-transcriptome assay (Veracyte, San Diego, CA) to generate PORTOS. The independent prognostic ability and interaction effects were examined for the biochemical progression, clinical progression-free survival (CPFS), receipt of salvage hormone therapy, and metastasis-free survival endpoints with Cox multivariable and interaction analyses (MVA). Categorical analyses used the published threshold for PORTOS radiotherapy response (high vs low). <h3>Results</h3> Of the 226 trial patients with transcriptome data, 16% had high PORTOS radiation response compared to 84% with lower PORTOS. Patients with high PORTOS were well balanced between the randomization arms. PORTOS was not prognostic for the endpoints in MVA with the trial stratification factors. A high PORTOS, however, was predictive for improved outcomes in patients receiving dose-intensified SRT. Patients with high PORTOS that received 70Gy dose had 5-year CPFS of 94% compared to 49% with the 64Gy dose (log-rank p=0.006). In interaction analysis, PORTOS had a statistically significant interaction with RT dose for multiple endpoints: freedom from biochemical progression (interaction p=0.04), clinical progression-free survival (interaction p=0.003) and metastasis-free survival (interaction p=0.037). <h3>Conclusion</h3> In a phase 3 trial testing SRT dose intensification after RP, patients with high PORTOS had significantly better outcomes with dose-intensified treatment, suggesting that higher doses should be considered in this subgroup. Further studies are warranted to validate PORTOS as the first predictive biomarker to help personalize dose prescription in the postoperative setting.

The Utility of Mean Apparent Diffusion Coefficient Value in Patients with Prostate Cancer Treated with Definitive Radiotherapy

<h3>Purpose/Objective(s)</h3> By providing more objective measurements, quantitative magnetic resonance imaging (MRI) has the potential to further improve prediction of treatment outcomes for prostate cancer patients. The purpose of this study was to determine whether quantitative multiparametric MRI performed prior to treatment can accurately predict the biochemical outcome of prostate cancer patients receiving definitive radiotherapy (RT). <h3>Materials/Methods</h3> The clinical data of 503 prostate cancer patients who received definitive radiation therapy (RT) between June 2008 and September 2021 were analyzed retrospectively. Prior to RT, all patients had a prostate multiparametric MRI on a 3T MRI scanner. A radiologist outlined the index lesion and measured the quantitative apparent diffusion coefficient (ADC). The Phoenix criteria were used to define biochemical failure. The primary endpoints were failure from biochemical failure (FFBF) and progression free survival (PFS). <h3>Results</h3> The median age of the population was 69 years (range: 47–87 years). According to D'Amico risk categories, there were 183 patients (36.4%) classified as low risk, 156 patients (31%) classified as intermediate risk, and 164 patients (32.6%) classified as high risk. The mean ADC values for tumor and normal prostate tissue were 0.712±0.158 µm²/ms and 1.365±0.227 µm²/ms, respectively (p<0.001). The ADC values were significantly lower in patients with higher PSA (≥20 ng/mL), advanced T stage (≥T3a), nodal metastasis, higher ISUP score (≥3) and high-risk group compared to their counterparts. The median duration of follow-up was 72.9 months (range, 4.3–170.6 months) for the entire cohort. The 5-year FFBF and PFS rates were 93.2% and 86.2%, respectively. Biochemical failure was observed in 42 patients (9.3%). After ‘Receiver Operating Characteristics' (ROC) curve analysis, the cut-off point of ADC for predicting high-risk progression was 0.653 µm²/ms with area under curve of 0.656 (95%CI 0.581 – 0.736; p<0.001). In univariate analysis, PSA, T stage, ISUP score, risk group were significant prognostic factors for FFBF and PFS. Additional prognostic factor for OS was N stage, and age was for PFS. The 5-year FFBF for lower and higher ADC values were 89.1% and 95.6%, respectively (p<0.001). The 5-year PFS was significantly less for patients with lower ADC compared to those with higher ADC (82.2% vs. 88.5%; p = 0.002). In multivariate analysis higher ISUP score and lower ADC values were independent predictors for worse FFBF and PFS rates. Additional predictive factor for dismal PFS was older age. <h3>Conclusion</h3> Our findings suggest that quantitative ADC values of the index lesion may be used to predict biochemical failure and disease progression in patients with prostate cancer following definitive RT. Inferior biochemical control was associated with lower ADC values and higher ISUP scores.

Prognostic Utility of (18)F-Fluciclovine Positron Emission Tomography (FACBC) in Biochemically Recurrent (BCR) Prostate Cancer (PCa) Treated with Salvage Radiotherapy

<h3>Purpose/Objective(s)</h3> Patients with a biochemical recurrence after definitive radiotherapy or prostatectomy often undergo imaging to localize recurrent disease prior to salvage treatment. FACBC is a commonly utilized scan for this, but little is known about the prognostic utility of imaging metrics derived from FACBC scans in this setting. <h3>Materials/Methods</h3> This single-center retrospective study included 167 patients (pts) who had FACBC for BCR between 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts who received salvage radiotherapy (SRT) were then identified and classified by whether their scan was positive or negative. Imaging metrics derived from positive scans included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion metabolism (TLM). Freedom from biochemical progression (FFBP) and overall survival (OS) were compared between pts with positive and negative scans according to the Kaplan-Meier method, and for the above imaging metrics dividing each metric by its median value. Cox regression analysis for the following covariates was also performed: number of recurrence sites, SUVmax, MTV, and TLM. <h3>Results</h3> 71 pts received SRT; 34 had positive scans. The median FFBP for all patients who received SRT was 130 weeks (range 58.4-244.9). There was a statistical difference in FFBP between patients with negative and positive scans (median 130 vs. 128 weeks, p=0.039), but no difference in OS (median 130 vs. 146 weeks, p = 0.140). Among pts with positive scans, there was no difference in FFBP when considering high vs. low SUVmax, MTV, or TLF. There was also no difference when these factors were analyzed via cox regression. <h3>Conclusion</h3> In this retrospective cohort of 71 pts with FACBC PET scans treated with SRT, pts with a negative FACBC had a longer time to biochemical progression, but this did not affect overall survival. Although SUVmax, MTV, and TLM have been shown to be prognostic in other cancers with other PET tracers, none were prognostic in this cohort.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed (“prostatic cancer”, “albumin”, “globulin”, “albumin to globulin ratio”) following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12–0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12–0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430–0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259–0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.

Efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer: A single-center study in Japan.

Cabazitaxel is a next-generation taxane that can prolong overall survival after docetaxel treatment in patients with metastatic castration-resistant prostate cancer. However, the efficacy of cabazitaxel varies among these patients. The clinical indicators of the prognosis after cabazitaxel treatment were analyzed. A retrospective review of patients who received cabazitaxel between February 2015 and June 2021 was performed. All patients had metastatic castration-resistant prostate cancer. Prognostic factors for prostate-specific antigen progression-free and overall survival were analyzed by Cox proportional-hazards analysis and the log-rank test. The study comprised 57 patients who received cabazitaxel (median 4 cycles, range 1-27) at a starting dose of 15-25 mg/m2 . The median age and follow-up duration were 70 years and 9.2 months. The median prostate-specific antigen progression-free survival and overall survival were 2.6 and 10.5 months, respectively. Univariate analysis showed that previous androgen receptor-axis-targeted therapy before cabazitaxel treatment was the only significant risk factor (hazard ratio 2.784, p = 0.022) for prostate-specific antigen progression-free survival. Multivariate analysis for overall survival revealed that poor performance status (≥1) (hazard ratio 2.107, p = 0.039), low hemoglobin (hazard ratio 0.142, p = 0.010), and high neutrophil-lymphocyte ratio (hazard ratio 9.150, p = 0.032) at baseline were significantly associated with a poor prognosis. Previous androgen receptor-axis-targeted therapy was the only risk factor for biochemical progression. Poor performance status, anemia, and high neutrophil-lymphocyte ratio were risk factors for poor prognosis in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel. These risk factors seem useful for identifying patients with survival benefit from cabazitaxel treatment.

The prognostic value of lymph node staging with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and extended pelvic lymph node dissection in node-positive patients with prostate cancer.

To investigate whether patients with suspected pelvic lymph node metastases (molecular imaging [mi] N1) on staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) had a different oncological outcome compared to those in whom the PSMA PET/CT did not reveal any pelvic lymph node metastases (miN0). All patients with pelvic lymph node metastatic (pN1) disease after robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) between January 2017 and December 2020 were included. To assess predictors of biochemical progression of disease after RARP, a multivariable Cox regression analysis was performed, including number of tumour-positive lymph nodes, diameter of the largest nodal metastasis, and extranodal extension. In total, 145 patients were diagnosed with pN1 disease after ePLND. The median biochemical progression-free survival in patients with miN0 on PSMA PET/CT was 13.7 months, compared to 7.9 months in patients with miN1 disease (P = 0.006). On multivariable Cox regression analysis, both number of tumour-positive lymph nodes (>2 vs 1-2: hazard ratio [HR] 1.97; P = 0.005) and diameter of the largest nodal metastasis (HR 1.12; P < 0.001) were significant independent predictors of biochemical progression of disease. Patients in whom pelvic lymph node metastases were suspected on preoperative PSMA imaging (miN1), patients diagnosed with >2 tumour-positive lymph nodes, and patients with a larger diameter of the largest nodal metastasis had a significantly increased risk of biochemical disease progression after surgery.

Evaluation of Risk Groups for the Prediction of Biochemical Progression in Patients Undergoing Radical Prostatectomy

Evaluation of Risk Groups for the Prediction of Biochemical Progression in Patients Undergoing Radical Prostatectomy

Sequential therapy with darolutamide in patients with non-metastatic castration-resistant prostate cancer resistant to enzalutamide or apalutamide.

Enzalutamide, apalutamide, and darolutamide are currently recommended for patients with non-metastatic castration-resistant prostate cancer (nmCRPC), but cross-resistance of androgen receptor-axis-targeted therapies (ARAT) occurs. Because darolutamide has a distinct chemical structure to other non-steroidal antiandrogens, it may be effective for nmCRPC patients resistant to enzalutamide or apalutamide. We retrospectively evaluated the efficacy of switching to darolutamide in patients with nmCRPC. We included nine nmCRPC patients who experienced biochemical progression on enzalutamide or apalutamide and were switched over to darolutamide. Five patients (55.5%) had a PSA response >50% decline after starting darolutamide, with an average of 73% PSA decline. Median progression-free survival was 6 months. In conclusion, an ARAT switch from enzalutamide or apalutamide to darolutamide might be effective for nmCRPC. Although the validation in a large-scale cohort is necessary, the switch to darolutamide could be a promising therapeutic option after the progression of 1st line ARAT in nmCRPC patients.

Oncological and urinary outcomes following low-dose-rate brachytherapy with a median follow-up of 11.8 years.

To examine the long-term oncological outcomes and urological morbidity of low-dose-rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate-risk prostate cancer. A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side-effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate-specific antigen (PSA) level of ≥0.2 μg/L. Minimum patient follow-up was 5.5 years. The median follow-up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9-17) μg/L and the median Gleason score was 3 + 4. The biochemical relapse-free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a 'surgical' definition of a PSA level of <0.2 μg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer-specific survival (PCSS) was 98% (291/297). Post-LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow-up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT. LDRBT is associated with excellent PCSS, with a median follow-up of 11.8 years. The risk of post-implantation urethral stricture and UI is low and a pre-implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture.

I-PET score: Combining whole body iodine and 18 F-FDG PET/CT imaging to predict progression in structurally or biochemically incomplete thyroid cancer.

We propose a new scoring system (I-PET) combining whole body scan (WBS)and FDG findings to identify patients who have or are likely to become refractory to radioactive iodine. Retrospective analysis of 142 patients age >18 withdifferentiated thyroid cancerwho had a F-18 labelled fluoro-2-deoxyglucose (18 F-FDG)positron emission tomography(PET) and WBS within a 6-month period between 2010 and 2020. Pairs of 18 F-FDG PET and WBS were reviewed by three independent nuclear medicine physicians and an I-PET score was assigned: I-PET[0]: Iodine -ve/FDG-ve, I-PET[1]:Iodine +ve/FDG-ve, I-PET[2]:Iodine +ve/FDG+ve and I-PET[3]:Iodine -ve/FDG+ve. Patients with FDG +velesions (I-PET[2] and I-PET[3]) were further classified into groups A and B if SUVmax was ≤5 or >5, respectively. Follow-up data were obtained by chart review. Progression was defined as structural progression as per RECIST 1.1 or further surgical intervention; or biochemical progression as unstimulated thyroglobulin increasing >20% from baseline. Of 142 patients included in the study 121 patients had follow-up data available for review. At baseline, 49 patients were classified as I-PET[0], 10 as I-PET[1], 16 as I-PET[2] and 46 as I-PET[3]. Progression was seen in 11/49 (22%) of I-PET[0], 4/10 (40%) of I-PET[1], 10/16 (63%) of I-PET[2] and 34/46 (74%) of I-PET[3] (p < 0.001). I-PET[2B] and I-PET[3B] had a progression rate of 88% (7/8) and 78% (25/32), respectively. I-PET[3B] were 9.6 times more likely to commence multikinase inhibitor therapy (p = 0.001) and had 8 times greater mortality (p = 0.003) than patients in other I-PET groups combined. I-PET is a simple readily acquired imaging biomarker that potentially enhances the dynamic risk stratification and guide treatment in thyroid cancer.

Salvage Nodal Radiotherapy as Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer Detected by Positron Emission Tomography Shows Favorable Outcome in Long-Term Follow-Up.

The study aimed to access the long-term outcome of salvage nodal radiotherapy (SNRT) in oligorecurrent prostate cancer. A total of 95 consecutive patients received SNRT for pelvic and/or extrapelvic nodal recurrence after prostate-specific membrane antigen (PSMA) or choline PET from 2010 to 2021. SNRT was applied as external beam radiotherapy with simultaneous integrated boost up to a median total dose of 62.9 Gy (EQD21.5Gy) to the recurrent lymph node metastases. The outcome was analyzed by cumulative incidence functions with death as the competing risk. Fine-Gray regression analyses were performed to estimate the relative hazards of the outcome parameters. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (v5.0). The results are as follows: the median follow-up was 47.1 months. The five-year biochemical progression rate (95% CI) was 50.1% (35.7-62.9%). Concomitant androgen deprivation therapy (ADT) was adminstered in 60.0% of the patients. The five-year biochemical progression rate was 75.0% (42.0-90.9%) without ADT versus 35.3% (19.6-51.4%) with ADT (p = 0.003). The cumulative five-year late grade 3 GU toxicity rate was 2.1%. No late grade 3 GI toxicity occured. Metastasis-directed therapy through SNRT for PET-staged oligorecurrent prostate cancer demonstrated a favorable long-term oncologic outcome. Omittance of ADT led to an increased biochemical progression.

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.

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan–Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.Study identifier at ClinicalTrials.gov: NCT01492751.

Single-nucleotide polymorphismassociations with efficacy and toxicity in metastatic castration-resistant prostate cancer treated with cabazitaxel.

<b>Background:</b> The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC). <b>Patients &amp; methods:</b> 56 SNPs in five genes (<i>CYP3A4</i>, <i>CYP3A5</i>, <i>ABCB1</i>, <i>TUBB1</i> and <i>CYP2C8</i>) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. <b>Results:</b><i>TUBB1</i>-rs151352 (hazard ratio: 0.52) and <i>CYP2C8</i>-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and <i>CYP2C8</i>-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. <i>ABCB1</i>-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and <i>CYP2C8</i>-rs11572093 with asthenia (odds ratio: 8.12). <b>Conclusion:</b> Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.

Immunophenotypic Characteristics of Bone Marrow Microenvironment Cellular Composition at the Biochemical Progression of Multiple Myeloma.

Multiple myeloma (MM) relapses are inevitable in the majority of patients, and in addition to genetic changes in the MM clone, the immune profile of the bone marrow (BM) plays a key role in this process. Biochemical progression or relapse (BR) precedes clinical relapse in a significant proportion of patients with MM. In the present study, we used flow cytometry to assess the cellular composition of the BM microenvironment in MM patients with confirmed BR. Fifteen distinct cells subsets in the BM were evaluated with the panel of antibodies used routinely for MRD monitoring in MM in 52 patients with MM (MRD-negative n = 20, BR n = 20, and clinically relapsed MM, RMM n = 12). The median percentage of MM cells detected in BR patients was 0.90% versus not detectable in MRD-negative patients and of 3.0% in RMM cohort. Compared to the MRD-negative group, BR status was associated with an increase in the percentage of lymphoid subpopulations, including memory B cells (p = 0.003), CD27+T cells (p = 0.002), and NK/NKT cells (p < 0.001). Moreover, a decrease in B-cell precursors (p < 0.001) and neutrophils (p = 0.006) was observed. There were no significant differences in the composition of the BM cell subpopulations between the BR and RMM groups. Our results indicate the involvement of B-, T-, and NK cells in the process of losing immune surveillance over the MM clone that leads to relapse. It can be speculated that similar studies of a larger cohort of BR patients can potentially identify a group of patients for which an early treatment intervention would be beneficial.