Biochemical Recurrence In Group Research Articles

A bicentric retrospective study of the correlation of EAU BCR risk groups with 18F-PSMA-1007 PET/CT detection in prostate cancer biochemical recurrence

The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy: ISUP < 4 and PSA doubling time (PSAdt) > 12 months for low risk, and ISUP ≥ 4 or PSAdt ≤ 12 months for high risk. This dual-center retrospective study aims to investigate the correlation between the EAU risk stratification for BCR following radical prostatectomy and the detection rate of lesions using 18F-PSMA-1007 PET/CT. Among the 71 included patients (58 high-risk, 13 low-risk), with a median PSA level of 1.43 ng/ml, PET/CT demonstrated a significantly higher positivity in the high-risk group compared to the low-risk group (72.4% vs. 38.0%, p = 0.026). Analysis of recurrence sites revealed a similar proportion of pelvic-confined disease in both groups (24.1% vs. 23.1%, p = 0.935), but a significantly higher incidence of metastatic disease in the high-risk group (51.7% vs. 15.4%, p = 0.017), with detailed findings indicating an increased prevalence of bone metastases in the high-risk BCR group (37.8% vs. 7.7%, p = 0.048). Therefore, PSMA PET/CT offers valuable insights for treatment decisions, aligning with the evolving landscape of prostate cancer management.

Contribution of 68 Ga-DOTA-FAPI-04 PET/CT to Prostate Cancer Imaging : Complementary Role in PSMA-Negative Cases.

Prostate-specific membrane antigen (PSMA)-targeted PET/CT is a well-established imaging method in prostate cancer (PC) for both staging and restaging, and also for theranostic applications. An alternative imaging method is crucial for 15% PSMA-negative cases. We aimed to investigate the contribution of 68 Ga-DOTA-FAPI-04 PET/CT to PC imaging. Thirty-six patients diagnosed with PC were included. Patients underwent both 68 Ga-PSMA PET/CT and 68 Ga-DOTA-FAPI-04 PET/CT imaging within 1 week. In staging group, primary tumor uptake values were compared, and also correlations were done with histopathological findings, MRI findings, and total PSA levels. In biochemical recurrence group, the uptake values in prostatic region and metastases were evaluated to define the local recurrence or metastatic disease. In staging group, PSMA PET showed increased uptake in the primary lesion area in 14/27 (52%) patients, whereas 20/27 (74%) patients were positive in FAPI-04 PET. FAPI-04 positivity was found to be quite high, such as 54%, in PSMA-negative patients. A significant difference was observed between ISUP grade 1-3 patients and ISUP grade 4-5 patients in FAPI-04 PET ( P = 0.03). Local recurrence was detected in 3 patients, pelvic lymph node metastasis in 1 patient, and sacrum metastasis in 1 patient in biochemical recurrence group, and all of the lesions had more intense uptake in PSMA PET than FAPI-04 PET. FAPI PET imaging seems to have a potential to contribute PSMA PET imaging with FAPI positivity in more than half of PSMA-negative cases. Also, FAPI-targeted radionuclide therapy may be a promising method in patients resistant to PSMA-targeted therapy.

Development and validation of a circulating tumor cells-related signature focusing on biochemical recurrence and immunotherapy response in prostate cancer

BackgroundStudies have shown that the circulating tumor cells (CTCs) play a key role for invasion and formation of distant metastases in prostate cancer (PCa). However, few CTCs-related genes (CRGs) have been developed for biochemical recurrence (BCR) prediction and clinical applications of PCa patients. Materials and methodsBioinformatics analysis with public PCa datasets were used to investigate the relationship between the differentially expressed CRGs and BCR. Lasso-COX regression analysis was used to constructed and validated a CRGs-based BCR prediction signature for PCa. Single-cell data were used to validate the expression levels of signature genes in different cell types and then explored the cell-cell communication relationships. Finally, the expression levels of signature genes were verified and the CRGs involved in immunotherapy response were further identified. ResultsThirteen CRGs were differentially expressed and closely associated with BCR in PCa. Then we constructed and validated a BCR prediction signature for PCa patients based on 3 differentially expressed CRGs (EMID1, SPP1 and UBE2C), and the signature was an independent factor to predict BCR for PCa. Single-cell data showed the specific expression patterns of the signature genes, while the SPP1 pathway plays an important role in cell-cell communication. Further analyses suggested UBE2C was highly expressed in BCR group and high expression of UBE2C had a better response for patients who received immunotherapy. Moreover, the expression levels of UBE2C in CTCs were higher than other cells and tissues, indicated that UBE2C may affect the BCR event of PCa patients through CTCs. ConclusionOur findings demonstrated that CRGs were significantly associated with BCR and immunotherapy efficacy in PCa and CRGs may influence the BCR event through CTCs.

European Association of Urology Biochemical Recurrence Risk Classification as a Decision Tool for Salvage Radiotherapy—A Multicenter Study

BackgroundThe European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP). ObjectiveTo assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT). Design, setting, and participantsAnalyses of 2379 patients who developed BCR after RP (1989–2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively. Outcome measurements and statistical analysisMultivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group. Results and limitationsOverall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1). ConclusionsImproved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up. Patient summaryThe impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR.

Establishment and Validation of a Novel Prediction Model for Early Natural Biochemical Recurrence After Radical Prostatectomy Based on Post-Operative PSA at Sixth Week.

Based on post-operative PSA at 6th week (PSA6w) after radical prostatectomy to establish an optimal model for predicting natural biochemical recurrence (BCR). A total of 742 patients with post-operative PSA6w from PC-follow database, between January 2003 and October 2022, were included. All the patients had not received any hormone therapy and radiotherapy before operation and BCR. Of these patients, 588 cases operated by one surgeon were enrolled for modelling and another 154 cases operated by other surgeons were for external validation. After screened by Cox regression, the post-operative PSA6w, pathological stage, Gleason Grade and positive surgical margins were adopted for modelling. The R software was used to plot the nomogram of the prediction model for BCR. C-index and calibration curve were calculated to evaluate the new model. Finally, integrated discrimination improvement was adopted to evaluate the prediction performances of the new nomogram model and the classical Kattan nomogram. The C-index of the new model was 0.871 (95% CI: 0.830-0.912). The calibration curve of the new model demonstrated superior consistency between the predicted and actual value. The C-index of the external validation group was 0.850 (95% CI: 0.742-0.958), which demonstrated perfect universality. The integrated discrimination improvement showed a 12.61% improvement in prediction performance over that of the classical Kattan nomogram (P < 0.01). Based on the new nomogram, patients were divided to high and low BCR group with a 3 year BCR-free cutoff probability as 74.72%. Low-risk patients, accounting for 77.89% of the patients, have no need to follow up frequently with a false-negative rate only 5.24%, which will save medical resources to a large extent. Post-operative PSA6w is a sensitive risk biomarker for early natural BCR. The new nomogram model could predict BCR probability with a higher accuracy and will further simplify the clinical follow-up strategies.

Prognostic value of estrogen receptors in patients who underwent prostatectomy for non‑metastatic prostate cancer.

Estrogen receptors in prostate cancer (PCa) are a subject of debate. The aim of the present study was to investigate whether estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) impact the biochemical recurrence (BCR) of non-metastatic PCa after surgery. Following the application of the exclusion criteria, data from 108 patients who underwent laparoscopic radical prostatectomy between January 2011 and December 2019 were retrospectively evaluated. A total of 36 patients with BCR constituted the BCR group. The control group was formed using the Propensity Score Matching (PSM) method with a 1:2 ratio, including parameters with well-studied effects on BCR. The median follow-up time was 74.3 (range, 30-127.5) months in the BCR group and 66.6 (range, 31.5-130) months in the control group. Pathology specimens from the two groups were immunohistochemically stained with ERα and ERβ antibodies. Logistic regression analysis and survival analysis were performed. No differences in clinicopathological characteristics were detected between the two groups. The patients with ERα(-)/ERβ(+) staining results had a significantly fewer BCRs than other patients (P=0.024). In the logistic regression analysis, patients with ERα(-)/ERβ(+) PCa also had a significantly lower risk of recurrence (P=0.048). In the survival analysis, the 5-year BCR-free survival rate of patients with ERα(-)/ERβ(+) PCa was higher than that of other patients (85.7 vs. 66.1%; P=0.031). Excluding the effects of well-studied risk factors for recurrence by the PSM method, the present study showed that ERα and ERβ have prognostic value for non-metastatic PCa. The 5-year BCR-free survival rate is significantly higher in patients whose PCa tissue has ERα(-)/ERβ(+) staining results.

Predicting Model of Biochemical Recurrence of Prostate Carcinoma (PCa-BCR) Using MR Perfusion-Weighted Imaging-Based Radiomics.

To build a combined model that integrates clinical data, contrast-enhanced ultrasound, and magnetic resonance perfusion-weighted imaging-based radiomics for predicting the possibility of biochemical recurrence of prostate carcinoma and develop a nomogram tool. We retrospectively analyzed the clinical, ultrasound, and magnetic resonance imaging data of 206 patients pathologically confirmed with prostate carcinoma and receiving radical prostatectomy at Xiangyang No. 1 People's Hospital from February 2015 to August 2021. Based on one to 7 years of follow-up (prostate specific antigen [PSA] level≥0.2 ng/mL, indicative of prostate carcinoma-biochemical recurrence), the patients were divided into biochemical recurrence group (n = 77) and normal group (n = 129). The training and testing sets were formed by dividing the patients at a 7:3 ratio. In training set, The magnetic resonance perfusion-weighted imaging-based radiomics radscore was generated using lasso regression. Several predictive models were built based on the patients' clinical imaging data. The predictive efficacy (area under the curve) of these models was compared using the MedCalc software. The decision curve analysis was conducted using the R to compare the net benefit. Finally, an external validation was carried out on the testing set, and the nomogram tool was developed for predicting prostate carcinoma-biochemical recurrence. The univariate analysis confirmed that Tumor diameter, tumor node metastasis classification stage of tumor, lymph node metastasis or distance metastasis, Gleason grade, preoperative PSA, ultrasound (peak intensity, arrival time, and elastography grade), and magnetic resonance imaging-radscore1/2 were predictors of prostate carcinoma-biochemical recurrence. On the training set, the combined model based on the above factors had the highest predictive efficacy for prostate carcinoma-biochemical recurrence (area under the curve: 0.91; odds ratio 0.02, 95% confidence interval: 0.85-0.95). The predictive performance of the combined model was significantly higher than that of the model based on general clinical data (area under the curve: 0.74; odds ratio 0.04, 95% confidence interval: 0.67-0.81, P < .05), contrast-enhanced ultrasound (area under the curve: 0.61; odds ratio 0.05 95% confidence interval: 0.53-0.69, P < .05), and the magnetic resonance imaging-based radiomics model (area under the curve: 0.85; odds ratio 0.03, 95% confidence interval: 0.78-0.91, P = .01). The decision curve analysis also indicated the maximum net benefit derived from the combined model, which agreed with the validation results on the testing set. The nomogram tool developed based on the combined model achieved a good performance in clinical applications. The magnetic resonance imaging texture parameters extracted by magnetic resonance perfusion-weighted imaging Lasso regression could help increase the accuracy of the predictive model. The combined model and the nomogram tool provide support for the clinical screening of the populations at a risk for biochemical recurrence.

Factors predicting biochemical recurrence following robot-assisted radical prostatectomy: single-center experience

Objective: In this study, we aimed to investigate factors predicting the development of biochemical recurrence (BCR) in our clinical experience with patients over a long follow-up.Material and Methods: The data of 758 patients who underwent robot-assisted radical prostatectomy (RARP) were retrospectively reviewed. In the postoperative period, the prostate-specific antigen (PSA) value is measured as 0.2 ng/mL and above, regarded as biochemical recurrence (BCR). The non-BCR group was regarded as Group 1, and the BCR group as Group 2.Results: The mean age was similar between the two groups. The PSA values ​​were significantly higher in the group that developed BCR (p&amp;lt;0.001). The biopsy Gleason score (GS), risk classification, and specimen GS were significantly higher in this group (p=0.02, p&amp;lt;0.001, and p&amp;lt;0.001, respectively). The BCR group also had statistically significantly higher positive surgical margin (PSM), extraprostatic extension (EPE), seminal vesicle invasion (SVI), and lymph node invasion rates. According to the multivariate analyses, PSA, risk classification, specimen GS, PSM, SVI, and T stage were significant parameters in the prediction of BCR.Conclusion: The parameters ​​that predict the development were determined as the PSA value, risk classification, specimen GS, PSM, SVI, and T stage. The widespread adoption of commonly accepted methods will help achieve better patient management and optimize patient expectations.

PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER Ashley Monaco, Jessica Sommer, Jordan Mendelson, Jonathan Haas, Anthony Corcoran, and Aaron Katz Ashley MonacoAshley Monaco More articles by this author , Jessica SommerJessica Sommer More articles by this author , Jordan MendelsonJordan Mendelson More articles by this author , Jonathan HaasJonathan Haas More articles by this author , Anthony CorcoranAnthony Corcoran More articles by this author , and Aaron KatzAaron Katz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While prostate specific antigen (PSA) bounce following radiation therapy for prostate cancer (PCa) treatment is well established, the parameters to predict this occurrence and differentiate it from biochemical recurrence (BCR) following stereotactic body radiotherapy (SBRT) are unknown. The purpose of this study is to investigate associations between pre-treatment and post-treatment variables among patients experiencing PSA bounce, BCR, or neither following SBRT. METHODS: An IRB-approved PCa database was reviewed for patients who underwent primary SBRT. Patients with less than 18 months of follow-up or were missing >3 PSA measurements following SBRT were excluded. Patients were divided into outcome groups experiencing PSA bounce, BCR, or neither. PSA bounce was defined as a rise of >0.2 ng/mL over the pre-rise nadir followed by a decline without intervention. BCR was defined by Phoenix criteria. Pre-treatment and post-treatment characteristics were analyzed between groups. Results that were significant when comparing PSA bounce to BCR were then analyzed in a multivariate logistic regression model to determine predictors for PSA bounce. RESULTS: We analyzed 170 men with a median age of 72 (52-87) years with an average follow-up time of 75 + 21 months, of which 28 (16%) experienced PSA bounce and 42 (25%) had BCR (Table 1). Pre-treatment D’Amico and Capra risk, Gleason group, PSA, prostate volume, prostate density and post-treatment PSA velocity were not associated with PSA bounce when compared to BCR or non-BCR/bounce cohorts. Compared to those who did not experience PSA bounce/BCR, those with PSA bounce were younger (p <.05), had lower PSA doubling time (p <.001), and took longer to reach PSA nadir (p <.001). Compared to BCR group, men with PSA bounce had lower PSA nadir and took longer to reach nadir, both of which were significant predictors for PSA bounce (OR: 4.3, p <.05; OR: 0.90, p <.001). PSA bounce occurred significantly earlier than BCR (16 vs. 33 months; p <.001). CONCLUSIONS: While there is overlap among patients who experience PSA bounce or BCR following SBRT, the timing of which the PSA rise occurs, the PSA nadir value, and the time to PSA nadir are useful variables in the management of a rising PSA in patients following SBRT. Source of Funding: Department of Urology, NYU Langone Hospital – Long Island © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e407 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashley Monaco More articles by this author Jessica Sommer More articles by this author Jordan Mendelson More articles by this author Jonathan Haas More articles by this author Anthony Corcoran More articles by this author Aaron Katz More articles by this author Expand All Advertisement PDF DownloadLoading ...

A Ferroptosis-Related Gene Prognostic Index Associated With Biochemical Recurrence and Radiation Resistance for Patients With Prostate Cancer Undergoing Radical Radiotherapy.

Background: Ferroptosis is a new type of programmed cell death which has been reported to be involved in the development of various cancers. In this study, we attempted to explore the possible links between ferroptosis and prostate cancer (PCa), and a novel ferroptosis-related gene prognostic index (FGPI) was constructed to predict biochemical recurrence (BCR) and radiation resistance for PCa patients undergoing radical radiotherapy (RRT). Moreover, the tumor immune microenvironment (TME) of PCa was analyzed. Methods: We merged four GEO datasets by removing batch effects. All analyses were conducted with R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish a network of transcriptional factor and competing endogenous RNA. Results: We established the FGPI based on ACSL3 and EPAS1. We observed that FGPI was an independent risk factor of BCR for PCa patients (HR: 3.03; 95% CI: 1.68–5.48), consistent with the result of internal validation (HR: 3.44; 95% CI: 1.68–7.05). Furthermore, FGPI showed high ability to identify radiation resistance (AUC: 0.963; 95% CI: 0.882–1.00). LncRNA PART1 was significantly associated with BCR and might modulate the mRNA expression of EPAS1 and ACSL3 through interactions with 60 miRNAs. Gene set enrichment analysis indicated that FGPI was enriched in epithelial–mesenchymal transition, allograft rejection, TGF beta signaling pathway, and ECM receptor interaction. Immune checkpoint and m6A analyses showed that PD-L2, CD96, and METTL14 were differentially expressed between BCR and no BCR groups, among which CD96 was significantly associated with BCR-free survival (HR: 1.79; 95% CI: 1.06–3.03). We observed that cancer-related fibroblasts (CAFs), macrophages, stromal score, immune score, estimate score, and tumor purity were differentially expressed between BCR and no BCR groups and closely related to BCR-free survival (HRs were 2.17, 1.79, 2.20, 1.93, 1.92, and 0.52 for cancer-related fibroblasts, macrophages, stromal score, immune score, estimate score, and tumor purity, respectively). Moreover, cancer-related fibroblasts (coefficient: 0.20), stromal score (coefficient: 0.14), immune score (coefficient: 0.14), estimate score (coefficient: 0.15), and tumor purity (coefficient: −0.15) were significantly related to FGPI, among which higher positive correlation between cancer-related fibroblasts and FGPI was observed. Conclusion: We found that FGPI based on ACSL3 and EPAS1 might be used to predict BCR and radiation resistance for PCa patients. CD96 and PD-L2 might be a possible target for drug action. Besides, we highlighted the importance of immune evasion in the process of BCR.

A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer

BackgroundWe aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa).MethodsWe used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsWe established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887.ConclusionsWe concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa.

Influence of the time interval between biopsy and surgery on the biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients

ObjectiveWe evaluated the impact of the duration between the biopsy and surgery on the biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). MethodsWe retrospectively evaluated 302 patients who underwent RARP in our institution from April 2010 to December 2017. Patients were categorized into 2 groups, an interval between biopsy and surgery of 180 days or less (Group A) and longer than 180 days (Group B). Factors retrospectively analyzed for the BCR for the interval between the biopsy and RARP included patient's characteristics, intraoperative and postoperative results. The Kaplan–Meier method and Cox proportional hazards regression model were used to evaluate the predictors of BCR. ResultsThe median follow-up was 42 months, with 24 patients developing BCR at a mean of 13.5 months after RARP. There was no difference in the rate of BCR in Group A and Group B. Multivariate analysis showed that BMI (<23.5 kg/m2, p = 0.034), worst GS of the biopsy (≥8, p = 0.007), and without lymph node dissection (p = 0.034) were significant predictors of BCR. Analysis of the interval from the biopsy showed that there was no significant difference between Group A and Group B, when tested according to the NCCN risk stratification (low risk: p = 0.871, intermediate risk: p = 0.205, high risk: p = 0.287). ConclusionThe preoperative predictors of BCR included BMI (<23.5 kg/m2) and worst GS of the biopsy, and without lymph node dissection. A long duration from biopsy to RARP did not influence the probability of BCR, even in patients considered to be at a high risk.

Can Dosiomics Features Be Relevant Predictive Factors for Biochemical Recurrence After Radiotherapy in Prostate Cancer Patients?

<h3>Purpose/Objective(s)</h3> Radiotherapy is one of the main treatment strategies for localized prostate cancer. Although several patients receive external radiotherapy, the relationships between dosimetric factors related to the treatment planning and biochemical recurrence (BCR) remain unclear. The aims of the present study were to develop a prediction model for BCR by integrating dose-based radiomics (dosiomics) features and clinical variables in prostate cancer patients, and to clarify the relationships between the dosimetric factors and BCR. <h3>Materials/Methods</h3> A total of 489 patients with adenocarcinoma of the prostate who had been prescribed a dose of 78 Gy in 39 fractions with intensity modulated radiation therapy from 2007 to 2014 were retrospectively enrolled. A total of 2,475 dosiomic features were calculated from the 3D doses in prostate, clinical target volume (CTV), and planning target volume (PTV), and relevant 8 clinical variables for BCR were also considered. Feature selection was performed to eliminate redundant or not significant features. Multivariate cox proportional hazards regression model was trained on the training cohort of 342 patients using the selected features, and the predictive performance was validated on the validation cohort of 147 patients using the concordance index (C-index). Kaplan-Meir curves with log-rank analysis was used to assess the univariate discrimination of freedom from biochemical failure (FFBF) between high- and low-risk BCR groups. <h3>Results</h3> A total of 96 patients developed BCR with the median time of 55.2 months. Two dosiomic features (1 from CTV and 1 from PTV) and three clinical variables were selected as predictive factors. Of the five, CTV (HGLRE) (hazard ratio [HR]: 0.73; 95% confidence intervals [CI]: 0.57-0.93; <i>P</i> = 0.01), pretreatment prostate-specific antigen (HR: 1.27; 95% CI: 1.04–1.55; <i>P</i> = 0.02) and positive biopsy core rate (HR: 1.40; 95% CI: 1.07–1.82; <i>P</i> = 0.01), were significantly associated with BCR. The C-index of the model in the validation cohort was 0.67 (95% CI: 0.65–0.68). CTV_wavelet-HHH_glrlm_HGLRE could significantly distinguish the patients into high- and low-risk groups (8-year FFBF: 76.6% vs. 87.5%, <i>P</i> < 0.01). <h3>Conclusion</h3> The dosiomic feature extracted from CTV can be a relevant predictive factor for BCR after radiotherapy in prostate cancer patients and may be useful as new metric for evaluating the quality of a treatment plan, instead of conventional dose indices.

Machine learning algorithms can more efficiently predict biochemical recurrence after robot-assisted radical prostatectomy.

To develop a model for predicting biochemical recurrence (BCR) in patients with long follow-up periods using clinical parameters and the machine learning (ML) methods. Patients who underwent robot-assisted radical prostatectomy between January 2014 and December 2019 were retrospectively reviewed. Patients who did not have BCR were assigned to Group 1, while those diagnosed with BCR were assigned to Group 2. The patient's demographic data, preoperative and postoperative parameters were all recorded in the database. Three different ML algorithms were employed: random forest, K-nearest neighbour, and logistic regression. Three hundred and sixty-eight patients were included in this study. Among these patients, 295 (80.1%) did not have BCR (Group 1), while 73 (19.8%) had BCR (Group 2). The mean duration of follow-up and duration until the diagnosis of BCR was calculated as 35.2 ± 16.7 and 11.5 ± 11.3 months, respectively. The multivariate analysis revealed that NLR, PSAd, risk classification, PIRADS score, T stage, presence or absence of positive surgical margin, and seminal vesicle invasion were predictive for BCR. Classic Cox regression analysis had an area under the curve (AUC) of 0.915 with a sensitivity and specificity of 90.6% and 79.8%. The AUCs for receiver-operating characteristic curves for random forest, K nearest neighbour, and logistic regression were 0.95, 0.93, and 0.93, respectively. All ML models outperformed the conventional statistical regression model in the prediction of BCR after prostatectomy. The construction of more reliable and potent models will provide the clinicians and patients with advantages such as more accurate risk classification, prognosis estimation, early intervention, avoidance of unnecessary treatments, relatively lower morbidity and mortality. The ML methods are cheap, and their powers increase with increasing data input; we believe that their clinical use will increase over time.

Testosterone Therapy in Men with Biochemical Recurrence and Metastatic Prostate Cancer: Initial Observations

Introduction: Although prostate cancer (PCa) has long been considered an absolute contraindication for testosterone therapy (TTh), growing literature suggests TTh may be safely offered to men with localized PCa. We here present a single-center series of men treated with TTh for relief of symptoms, despite having more advanced disease, namely biochemical recurrence (BCR) or metastatic PCa (MET). Methods: We identified men treated with TTh with BCR, MET, or adjuvant androgen deprivation therapy (ADT). Consent included risks of rapid PCa progression and death. Laboratory and clinical results were analyzed. Results: Twenty-two men received TTh: 7 with BCR, 13 with MET, and 2 with adjuvant ADT. Median age was 70.5 years (range 58–94). Median TTh duration was 12 months (range 2–84) overall, including 20 months for BCR and 9.5 months for MET. Mean serum testosterone (T) increased from 210 to 1111 ng/dL. Median PSA (interquartile range) increased from 3.1 ng/mL (0.2–4.5) to 13.3 ng/mL (3.4–22) in the BCR group, 6.3 ng/mL (1.2–31) to 17.8 ng/mL (6.2–80.1) in the MET group, and <0.1 to 0.3 ng/mL in the ADT group. All patients reported symptom relief, especially improved vigor and well-being. Overall mortality was 13.6% and PCa-specific mortality was 4.5% during the period of TTh and 6 months after discontinuation. Seven of 10 with follow-up imaging within 12 months showed no progression. Five men have died: three during TTh and two succumbed at 2 years or longer after discontinuing TTh. One of the three deaths during TTh was PCa-specific. Three men developed significant bone pain at 7–41 months; two discontinued TTh and one continued, after focal radiation. There were no cases of rapid-onset complications, vertebral collapse, or pathological fracture. Conclusions: These initial observations indicate TTh was not associated with precipitous progression of PCa in men with BCR and MET, suggesting a possible role for TTh in selected men with advanced PCa whose desire for improved quality of life is paramount.

P1171 - Machine learning algorithms can more efficiently predict biochemical recurrence after robot assisted radical prostatectomy

Objectives To develop a model for predicting biochemical recurrence (BCR) in patients with long follow-up periods using clinical parameters and the machine learning (ML) methods. Materials method Patients who underwent robot-assisted radical prostatectomy between January 2014 and December 2019 were retrospectively reviewed. Patients who did not have BCR were assigned to Group 1, while those diagnosed with BCR were assigned to Group 2. The patient's demographic data, preoperative and postoperative parameters were all recorded in the database. Three different ML algorithms were employed: random forest, K-nearest neighbour, and logistic regression. Results Three hundred and sixty-eight patients were included in this study. Among these patients, 295 (80.1%) did not have BCR (Group 1), while 73 (19.8%) had BCR (Group 2). The mean duration of follow-up and duration until the diagnosis of BCR was calculated as 35.2 ± 16.7 and 11.5 ± 11.3 months, respectively. The multivariate analysis revealed that NLR, PSAd, risk classification, PIRADS score, T stage, presence or absence of positive surgical margin, and seminal vesicle invasion were predictive for BCR. Classic Cox regression analysis had an area under the curve (AUC) of 0.915 with a sensitivity and specificity of 90.6% and 79.8%. The AUCs for receiver-operating characteristic curves for random forest, K nearest neighbour, and logistic regression were 0.95, 0.93, and 0.93, respectively. All ML models outperformed the conventional statistical regression model in the prediction of BCR after prostatectomy. Conclusion The construction of more reliable and potent models will provide the clinicians and patients with advantages such as more accurate risk classification, prognosis estimation, early intervention, avoidance of unnecessary treatments, relatively lower morbidity and mortality. The ML methods are cheap, and their powers increase with increasing data input; we believe that their clinical use will increase over time.

Biochemical recurrence after radical prostatectomy according to nadir prostate specific antigen value.

The hypersensitive prostate specific antigen (PSA) test can measure in 0.01 ng/mL units, and its efficacy for screening after radical prostatectomy (RP) has been reported. In this study, we assessed patients who underwent RP to evaluate whether the nadir value affects biochemical recurrence (BCR). From 1995 to 2014, patients classified as N0 who had negative resection margins and a nadir PSA of less than 0.2 ng/mL were evaluated. The characteristics, pathological outcomes, PSA after RP, and BCR were assessed. A total of 1483 patients were enrolled. Among them, 323 (21.78%) patients showed BCR after RP. The mean age of the BCR group was 63.86±7.31 years, and while that of the no-recurrence group was 64.06±6.82 years (P = 0.645). The mean preoperative PSA of the BCR group was 9.75±6.92 ng/mL and that of the no-recurrence group was 6.71±5.19 ng/mL (P < 0.001). The mean time to nadir (TTN) in the BCR group was 4.64±7.65 months, while that in the no-recurrence group was 7.43±12.46 months (P < 0.001). The mean PSA nadir value was 0.035±0.034 ng/mL in the BCR group and 0.014±0.009 ng/mL in the no-recurrence group (P < 0.001). In multivariable Cox regression analyses, Gleason score, positive biopsy core percentages, minimal invasive surgery, nadir PSA value, and TTN were independently associated with BCR. The mean BCR occurred at 48.23±2.01 months after RP, and there was a significant difference in BCR occurrence according to the nadir PSA value (P < 0.001). A high PSA nadir value and short TTN may predict the risk of BCR after successful RP, aiding the identification of candidates for adjuvant or salvage therapies after RP.

Construction and Validation of a Robust Cancer Stem Cell-Associated Gene Set-Based Signature to Predict Early Biochemical Recurrence in Prostate Cancer.

Background Postoperative early biochemical recurrence (BCR) was an essential indicator for recurrence and distant metastasis of prostate cancer (PCa). The aim of this study was to construct a cancer stem cell- (CSC-) associated gene set-based signature to identify a subgroup of PCa patients who are at high risk of early BCR. Methods The PCa dataset from The Cancer Genome Atlas (TCGA) was randomly separated into discovery and validation set. Patients in discovery set were divided into early BCR group and long-term survival group. Propensity score matching analysis and differentially expressed gene selection were used to identify candidate CSC-associated genes. The LASSO Cox regression model was finally performed to filter the most useful prognostic CSC-associated genes for predicting early BCR. Results By applying the LASSO Cox regression model, we built a thirteen-CSC-associated gene-based early BCR-predicting signature. In the discovery set, patients in high-risk group showed significantly poorer BCR free survival than that patients in low-risk group (HR: 4.91, 95% CI: 2.75–8.76, P < 0.001). The results were further validated in the internal validation set (HR: 2.99, 95% CI: 1.34–6.70, P = 0.005). Time-dependent ROC at 1 year suggested that the CSC gene signature (AUC = 0.800) possessed better predictive value than any other clinicopathological features in the entire TCGA cohort. Additionally, survival decision curve analysis revealed a considerable clinical usefulness of the CSC gene signature. Conclusions We successfully developed a CSC-associated gene set-based signature that can accurately predict early BCR in PCa cancer.

Factors affecting biochemical recurrence of prostate cancer after radical prostatectomy in patients with positive and negative surgical margin.

PurposeTo investigate the clinical and pathological predictive factors affecting biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with positive and negative surgical margin (SM).MethodsPatients who underwent RP were retrospectively reviewed for the study. Demographic, clinical, pathological and oncological data were evaluated. All data were compared between patients with positive SM and negative SM to detect factors associated with SM status. Later, patients were divided into two groups as BCR-negative and BCR-positive groups. Data were separately compared between BCR groups for all patients, SM-negative and SM-positive patients, respectively.ResultsA total of 254 patients with a mean age of 63.5 years and the mean prostate-specific antigen of 10.9 ng/ml were evaluated in the study. SM positivity was found to be an independent prognostic factor for BCR (p = 0.013, Odds Ratio (OR): 0.267, 95% Confidence Interval (CI): 0.094-0.755). In SM-positive patients, biopsy Gleason Score and International Society of Urological Pathology grade were found to be independent predictive factors for BCR (p < 0.05). However, only tumor to SM distance (TSMD) was found to be an independent risk factor for BCR (p = 0.024) in SM-negative patients. The predictive cutoff value of the TSMD was found to be 75 μm for BCR (100% sensitivity and 63.9% specificity) (AUC = 0.803, p = 0.024). Although all of 46 patients with >75 μm TSMD were recurrence free, 5 of 31 patients with <75 μm TSMD had BCR (p = 0.009; OR: 0.839 CI: 0.719–0.979).ConclusionHigh Gleason Score and International Society of Urological Pathology grade of biopsy were found to be associated with BCR in SM-positive patients. For SM-negative patients, only TSMD was found to be associated with BCR after RP.

PSMA whole-body tumor burden in primary staging and biochemical recurrence of prostate cancer.

The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed. Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p= < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV. PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.