Biochemical Recurrence Of Prostate Cancer Research Articles

Genetic variant located on chromosome 17p12 contributes to prostate cancer onset and biochemical recurrence

The genetic contribution to prostate cancer (PC) onset and clinical heterogeneity has an important impact on the disease stratification accuracy. Despite the fact that radical prostatectomy (RP) is an effective treatment for localized PC, a considerable number of individuals develop biochemical recurrence (BCR) following surgery. In the present study, we decided to investigate the significance of genetic variability in a homogeneous group of Romanian men and to determine if genotyping could provide information regarding the possible implications of rs4054823 susceptibility loci in PC progression and outcome. A total of 78 samples from both PC and benign prostatic hyperplasia (BPH) patients were genotyped. The genotype frequencies were examined to see if there was a link between the 17p12 SNP and PC disease. When compared to the BPH group, the PC group had a significantly higher frequency of the T risk variant (P = 0.0056) and TT genotype (P = 0.0164). Subsequent analysis revealed that the TT genotype had a significantly higher frequency among younger PC patients based on their age at diagnosis and that it was related with a greater probability of BCR (P = 0.02). According to our findings, the TT genotype appears to be a risk factor for early-onset PC and a potential predictor for BCR after RP.

18F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Curative-Intent Radiation Therapy: A Bicentric Retrospective Study.

This bicentric, retrospective analysis investigated the efficacy of PET/CT with a novel theranostic prostate-specific membrane antigen (PSMA)--targeting ligand, 18F-rhPSMA-7, in patients with biochemical recurrence (BCR) of prostate cancer after curative-intent primary radiotherapy. Methods: Datasets from patients with BCR of prostate cancer after external-beam radiation therapy or brachytherapy who underwent 18F-rhPSMA-7 PET/CT at either Technical University Munich or Ludwig-Maximilians-University Munich were retrospectively reviewed by experienced nuclear medicine physicians and radiologists at both centers. The median injected activity was 299 MBq (range, 204-420 MBq), and the median uptake time was 77 min (range, 46-120 min). All lesions suggestive of recurrent prostate cancer were noted. Detection rates were correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior use of androgen-deprivation therapy (ADT). Results: Ninety-seven patients were included (65 at Technical University Munich and 32 at Ludwig-Maximilians-University Munich). The median prescan PSA was 4.19 ng/mL (range, 0.1-159 ng/mL). The primary Gleason score was ≤6 in 19 patients, 7 in 25, ≥8 in 33, and unknown in 20. Thirty patients received ADT in the 6 mo preceding PET/CT. 18F-rhPSMA-7 identified lesions in 91 of 97 (94%) patients. Detection rates stratified by PSA were 88% (22/25), 97% (30/31), 90% (19/21), and 100% (20/20) for a PSA of <2, 2-<5, 5-<10, and ≥10 ng/mL, respectively. Detection rates in the subgroup of patients not meeting the Phoenix criteria for BCR were 80% (4/5), 90% (9/10), 100% (4/4), and 83% (5/6) for a PSA of <0.5, 0.5-<1, 1-<1.5, and 1.5-2 ng/mL, respectively. There were no significant differences in detection rates between patients with and without prior ADT (100% vs. 91%, P = 0.173) or patients with a Gleason score of ≤7 and a Gleason score of ≥8 (98% vs. 91%, P = 0.316).18F-rhPSMA-7 revealed local recurrence in 80% (78/97); pelvic lymph node metastases in 38% (37/97); retroperitoneal and supradiaphragmatic lymph node metastases in 9% (9/97) and 4% (4/97), respectively; bone metastases in 27% (26/97); and visceral metastases in 3% (3/97). In the subgroup of patients with a PSA of <2 ng/mL above nadir, local recurrence occurred in 76% (19/25) and pelvic lymph node metastases in 36% (9/25). Conclusion:18F-rhPSMA-7 PET/CT demonstrates high detection rates in prostate cancer patients with BCR after primary radiation therapy, even at low PSA values. Its diagnostic efficacy is comparable to published data for other PSMA ligands.

Is there a diagnostic benefit of late-phase abdomino-pelvic PET/CT after urination as part of whole-body 68\xa0Ga-PSMA-11 PET/CT for restaging patients with biochemical recurrence of prostate cancer after radical prostatectomy?

BackgroundTo assess the diagnostic value of an additional late-phase PET/CT scan after urination as part of 68 Ga-PSMA-11 PET/CT for the restaging of patients with biochemically recurrent prostate cancer (BCR).MethodsThis retrospective trial included patients with BCR following radical prostatectomy, who underwent standard whole-body early-phase PET/CT performed 105 ± 45 min and an additional late-phase PET/CT performed 159 ± 13 min after injection of 68 Ga-PSMA-11. Late-phase PET/CT covered a body volume from below the liver to the upper thighs and was conducted after patients had used the bathroom to empty their urinary bladder. Early- and late-phase images were evaluated regarding lesion count, type, localisation, and SUVmax. Reference standard was histopathology and/or follow-up imaging.ResultsWhole-body early-phase PET/CT detected 93 prostate cancer lesions in 33 patients. Late-phase PET/CT detected two additional lesions in two patients, both local recurrences. In total, there were 57 nodal, 28 bone, and 3 lung metastases, and 7 local recurrences. Between early- and late-phase PET/CT, lymph node metastases showed a significant increase of SUVmax from 14.5 ± 11.6 to 21.5 ± 17.6 (p = 0.00007), translating to a factor of + 1.6. Benign lymph nodes in the respective regions showed a significantly lower increase of SUVmax of 1.4 ± 0.5 to 1.7 ± 0.5 (p = 0.0014, factor of + 1.2). Local recurrences and bone metastases had a SUVmax on late-phase PET/CT that was + 1.7 and + 1.1 times higher than the SUVmax on early-phase PET/CT, respectively.ConclusionIn patients with BCR following radical prostatectomy, an additional abdomino-pelvic late-phase 68 Ga-PSMA-11 PET/CT scan performed after emptying the urinary bladder may help to detect local recurrences missed on standard whole-body 68 Ga-PSMA-11 PET/CT. Lymph node metastases show a higher SUVmax and a stronger increase of SUVmax than benign lymph nodes on late-phase PET/CT, hence, biphasic 68 Ga-PSMA-11 PET/CT might help to distinguish between malignant and benign nodes. Bone metastases, and especially local recurrences, also demonstrate a metabolic increase over time.

18F-Fluciclovine versus PSMA PET Imaging in Primary Tumor Detection during Initial Staging of High-Risk Prostate Cancer: A Systematic Review and Meta-Analysis.

Purpose Fluorine 18 (18F)-fluciclovine and prostate-specific membrane antigen (PSMA) tracers are commonly used for localizing biochemical recurrence of prostate cancer, but their accuracy in primary tumor detection in the initial staging of high-risk prostate cancer has not been established. Materials and Methods A systematic review was performed of the electronic databases for original studies published between 2012 and 2020. Included studies were those in which 18F-fluciclovine or PSMA PET was used for initial staging of patients with high-risk prostate cancer. The diagnostic performance data were collected for primary tumor with histopathologic results as reference standard. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for quality appraisal. A random-effects model was used to summarize the effect sizes and to evaluate the difference between two groups. Results Overall, 28 studies met the eligibility criteria, and 17 were included in the meta-analysis (18F-fluciclovine = 4, PSMA = 13). Of these 17 studies, 12 (70%) were judged to have high risk of bias in one of the evaluated domains, and nine studies were deemed to have applicability concerns. The pooled sensitivity, specificity, and diagnostic odds ratio for 18F-fluciclovine versus PSMA were 85% (95% CI: 73%, 92%) versus 84% (95% CI: 77%, 89%) (P = .78), 77% (95% CI: 60%, 88%) versus 83% (95% CI: 76%, 89%) (P = .40), and 18.88 (95% CI: 5.01, 71.20) versus 29.37 (95% CI: 13.35, 64.60) (P = .57), respectively, with no significant difference in diagnostic test accuracy. Conclusion 18F-fluciclovine and PSMA PET demonstrated no statistically significant difference in diagnostic accuracy in primary tumor detection during initial staging of high-risk prostate cancer. Keywords: PET, Prostate, Molecular Imaging-Cancer, Staging Supplemental material is available for this article. © RSNA, 2022.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy

Background/aimProstate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment.Materials and methodsThis analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan–Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy.ResultsOne-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43–1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5–40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53–1.28] vs 0.51 [IQR: 0.36–0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7–11.6] vs 12.7 [IQR: 6.6–24.3] months) (p < 0.001) compared to event-free patients. The Kaplan–Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001).ConclusionLow PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

A phase I does-escalation and expansion study of epidiolex (cannabidiol) in patients with biochemically recurrent prostate cancer.

257 Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have anti-tumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients’ prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily; two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in &gt;10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease. Clinical trial information: NCT04428203.

Trial in progress: Durvalumab and olaparib for the treatment of prostate cancer in men predicted to have a high neoantigen load.

TPS202 Background: Approximately 30% of patients (pts) treated with definitive surgical and/or radiation therapy for localized prostate adenocarcinoma develop biochemical recurrence (BCR). The optimal time to initiate androgen deprivation therapy (ADT) for such patients is controversial and depends on patient and provider preference, absolute PSA value, and PSA doubling time (PSADT), which has been associated with time to metastasis. Because the time from BCR to metastasis can be long in many cases, strategies allowing pts to avoid ADT while extending metastasis-free survival are desirable. Prior studies have shown that a high tumor neoantigen load correlates with response to anti-PD(L)1. We hypothesized that PARP inhibitor-induced genomic instability may sensitize tumors to anti-PD(L)1 through: i) increasing mutational burden and subsequent tumor neoantigen formation, and/or ii) through activation of other immunogenic pathways (e.g. the STING pathway). This trial investigates an ADT-sparing approach for men predicted to have high neoantigen load and who have BCR prostate cancer. Methods: This is a phase 2 clinical trial testing durvalumab (1500 mg IV every 4 weeks) and olaparib (300 mg PO twice a day) (one cycle = 4 weeks) in men with BCR (PSADT≤10 months) whose tumors are predicted to have high neoantigen load based on: biallelic CDK12 mutations (Cohort A), mismatch repair deficiency (MMRd)/high microsatellite instability (MSI-H) (Cohort B), or loss of function mutations in homologous recombination repair (HRR) genes (Cohort C). Cohorts A and B will receive 3 cycles of durvalumab followed by 3 cycles of the combination of durvalumab and olaparib. Given the proven efficacy of olaparib in prostate cancer patient whose tumors posses an HRR gene mutation, Cohort C will receive 6 full cycles of the combination. Ten patients will be enrolled in each cohort (total n = 30) at two collaborating sites. This study was designed to provide preliminary efficacy data across eligible cohorts, with a primary objective of estimating the proportion of pts with an undetectable PSA at 12 months within each cohort. Secondary objectives include safety, proportion of patients with ≥50% decline in PSA from baseline and quality of life measures. Correlative studies will assess blood and tissue molecular biomarkers for association with outcomes. The study is open with two patients enrolled at the time of abstract submission. Clinical trial information: NCT04336943.

A0190 - Optimizing timing and indications for 68Ga-PSMA PET/CT in patients with biochemical recurrent prostate cancer after radical prostatectomy

A0190 - Optimizing timing and indications for 68Ga-PSMA PET/CT in patients with biochemical recurrent prostate cancer after radical prostatectomy

A0198 - The key role of concomitant androgen-deprivation therapy on the efficacy of imaging guided treatments in men with biochemical recurrent prostate cancer after radical prostatectomy and 68Ga-PSMA PET/CT scan

A0198 - The key role of concomitant androgen-deprivation therapy on the efficacy of imaging guided treatments in men with biochemical recurrent prostate cancer after radical prostatectomy and 68Ga-PSMA PET/CT scan

A0821 - Metabolomics of Black-White differences in risk of prostate cancer biochemical recurrence

A0821 - Metabolomics of Black-White differences in risk of prostate cancer biochemical recurrence

Diagnostic accuracy of [18F]PSMA-1007 PET/CT in biochemical recurrence of prostate cancer

AimDespite increasing use for the detection of biochemically recurrent prostate cancer (rPC), the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) with [18F]PSMA-1007 remains only partially investigated. The aim of this study was to determine the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for PC-local recurrence and metastases on a per region basis.Materials and methodsOne hundred seventy-seven consecutive patients undergoing [18F]PSMA-1007 PET/CT for rPC were retrospectively analysed. Six body regions were defined: prostate fossa, pelvic lymph nodes (LN), retroperitoneal LN, supradiaphragmatic LN, bones, and soft tissue. A region was counted positive if at least one PSMA-positive lesion suspicious for PC was observed. Confirmation of a true-positive PSMA-avid lesion was defined as positive by histopathology, fall in serum prostate-specific antigen (PSA) (> 50%) after targeted therapy or confirmatory further CT, MRI, PET/CT, or bone scan imaging. Regions where additional imaging was able to confirm the absence of suspicious PC lesions or regions outside exclusively targeted RT with serum PSA decline (> 50%) were counted as true-negative regions. SE, SP, PPV, and NPV were calculated for all six regions.ResultsThe overall PET-positivity rate was 91%. Conclusive follow-up for affirmation or refutation of a PSMA-positive lesion was available for 81/152 patients on a per region basis. In this subgroup, overall sensitivity, specificity, PPV, and NPV were 95% (CI: 0.90–0.98), 89% (CI: 0.83–0.93), 86% (0.80–0.90), and 96% (CI: 0.92–0.98), respectively. On a per region basis, PPV was 97% (CI: 0.83–0.99) for local recurrence, 93% (CI: 0.78–0.98) for pelvic LN, 87% (CI: 0.62–0.96) for retroperitoneal LN, 82% (CI: 0.52–0.95) for supradiaphragmatic LN, and 79% (0.65–0.89) for bone lesions. The number of solid organ metastases (n = 6) was too small for an accurate statistical analysis.ConclusionThe known high PET-positivity rate of [18F]PSMA-1007 PET/CT in rPC was confirmed, with corresponding high (> 90%) sensitivity and NPV on a per region basis. However, overall PPV was limited (86%), particularly for bone lesions (79%), which are a potential diagnostic weaknesses when using this tracer.

Risk model based on MRI fusion biopsy characteristics predicts biochemical recurrence after radical prostatectomy.

To determine the prostate cancer biochemical recurrence-related fusion biopsy characteristics before radical surgery and to establish the risk prediction model of biochemical recurrence of prostate cancer. Three hundred and four patients undergoing radical surgery for prostate cancer at Huadong Hospital affiliated to Fudan University between 2009 and 2020 for preoperative magnetic resonance imaging (MRI) before biopsy with suspicious prostate cancer lesions. Each case was followed by a 10 + x needle combination of targeted biopsy (intentional or robotic fusion) with systematic biopsy. Prostate-specific antigen levels were measured at 1, 3, and 6 months postoperatively, followed by reexamination every 6 months. Survival analysis was performed by the Kaplan-Meier method, univariate and multivariate analysis by Cox, and Logistic risk regression models. Higher Prostate Imaging Reporting And Data System (PI-RADS) scores (p < 0.001), suspicious extracapsular invasion (p < 0.001), and seminal vesicle invasion (p < 0.001) on MRI, the largest lesion diameter on MRI (p = 0.006), higher biopsy International Society of Urological Pathology (ISUP) grade group (p < 0.001) related to higher biochemical recurrence rates, higher pathological staging (p < 0.001), and a greater probability of local lymph node metastasis (p < 0.001). We accurately predicted the biochemical recurrence of prostate cancer after radical surgery based on preoperative features including the long diameter of the largest MRI lesion more than 23 mm, seminal vesicle invasion on MRI, and targeted fusion biopsy ISUP grade >3 Risk stratified classification (AUC = 0.729, p < 0.001). In our cohort, this risk stratification had a larger area under the curve than predictive models based only on magnetic resonance parameters and traditional risk scores. In this cohort, seminal vesicle invasion on MRI, the long diameter of the largest MRI lesion, and targeted fusion biopsy ISUP grade grope are significantly predictive of pathologic features and biochemical recurrence after prostate surgery. The risk stratification integrating the three parameters could better predict the biochemical recurrence than the traditional model.

Identification of a Ubiquitin Related Genes Signature for Predicting Prognosis of Prostate Cancer.

Background: Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear. Methods: The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the “sva” R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated. Results: A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa. Conclusion: Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.

Detection Rate and Clinical Impact of PET/CT with 18F-FACBC in Patients with Biochemical Recurrence of Prostate Cancer: A Retrospective Bicentric Study.

Our aim was to assess the detection rate (DR) of positron emission computed tomography (PET/CT) with anti-1-amino-3-[18F]-flurocyclobutane-1-carboxylic acid (18F-FACBC) in patients with biochemical recurrence (BCR) from prostate cancer (PC). As a secondary endpoint, we evaluated 18F-FACBC PET/CT’s impact on patients management. Clinical records of 81 patients submitted to 18F-FACBC PET/CT due to PC BCR in two Italian Nuclear Medicine Units were retrospectively assessed. DR was gauged in the whole cohort and stratifying patients by discrete intervals of PSA levels. PET/CT’s impact on clinical management was scored as (1) major if it entailed an intermodality change (e.g., from systemic to loco-regional therapy); (2) minor if it led to an intramodality change (e.g., modified radiotherapy field). PET/CT’s DR resulted in 76.9% in the whole cohort, with a positive predictive value of 96.7%. Stratified by PSA quartile intervals, PET/CT’s DR was 66.7%, 71.4%, 78.9% and 90% for PSA 0.2–0.57 ng/mL, 0.58–0.99 ng/mL, 1–1.5 ng/mL and >1.5 ng/mL without significant difference among groups (p = 0.81). The most common sites of relapse were prostate bed and pelvic lymph nodes (59.3%). PET/CT impacted on clinical management in 33/81 cases (40.7%), leading to a major change in 30 subjects (90.9%). 18F-FACBC PET/CT localized recurrence in patients with BCR, with meaningful DR also at low PSA levels and significantly impacted on clinical management.

Moderately hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer after prostatectomy: long-term results and comparative analysis of two schedules.

Hypofractionation in salvage radiotherapy (HSRT) for biochemical recurrence of prostatic cancer after prostatectomy is a debated issue and at present, it should be considered purely investigational because of the lack of evidence supporting its use. In this study, we report the outcomes of patients presenting with biochemical recurrence after radical prostatectomy who received HSRT. The additional aim of this study is to compare two moderately HSRT schedules. Patients treated to prostate bed with daily Image Guided-VMAT and a total dose of 65 Gy/26 fractions (Group A) or 66 Gy/30 fractions (Group B) were included in the study. Inclusion criteria were: pN0/pNx, pre-HSRT PSA ≥0.2 ng/ml and ≤1 ng/ml, no evidence of pelvic/extrapelvic disease at restaging, no pelvic irradiation or dose boost on macroscopic local recurrence, no neoadjuvant/concomitant Androgen Deprivation Therapy (ADT), follow-up ≥36 months, and available pre/post HSRT data. Genitourinary (GU) and gastrointestinal (GI) toxicities, early and late, were assessed using CTCAE Vers. 5.0. One hundred patients were retrospectively identified to 50 in each group. Median follow-up was 59 months. All patients completed the prescribed HSRT. 5-year biochemical failure-free survival, local control, distant relapse-free survival, and ADT- free survival were 52.1%, 85.9%, 63.7%, and 73.2%, respectively. No significant differences in these outcomes were found between the two groups. On multivariate analysis, a hypofractionation schedule was not associated with any outcome, but ISUP score ≥ 4 and pre-HSRT PSA were associated with worse biochemical failure-free survival while only ISUP score ≥ 4 was associated with worse distant relapse-free survival. No Grade 3 GU/GI acute event was reported; 6 (6%) and 2 (2%) patients experienced late Grade ≥ 2 GU and GI events, respectively. No difference was found between the two groups neither in acute nor in late GU/GI toxicities. Our findings demonstrate that HSRT is feasible, effective, and safe. Our analysis did not show any significant difference between the two hypofractionated schedules. Further studies and randomized controlled trials are required in order to confirm these results and to identify the optimal hypofractionated schedule in the salvage setting.

Regional Analgesia Does Not Reduce Cancer Recurrence. Case closed

Regional Analgesia Does Not Reduce Cancer Recurrence. Case closed

Prediction of Prostate Cancer Biochemical Recurrence by Using Discretization Supports the Critical Contribution of Extra-Cellular Matrix Genes

Prediction of Prostate Cancer Biochemical Recurrence by Using Discretization Supports the Critical Contribution of Extra-Cellular Matrix Genes

Semiautomatic assessment of whole-body tumor burden with 18F-PSMA-1007 in biochemical recurrent prostate cancer.

The aim of the study was to evaluate the 18F-PSMA-1007 PET/computed tomography (CT) semiautomatic volumetric parameters to assess the whole-body tumor burden and its correlation with prostate-specific antigen (PSA) and Gleason score in patients with biochemically recurrent prostate cancer (PCa). A total of 110 patients referred for 18F-PSMA-1007 PET/CT due to biochemical recurrence were retrospectively analyzed. Whole-body total lesion prostate-specific membrane antigen (wbTl-PSMA) and whole-body PSMA-derived tumor volume (wbPSMA-TV) metrics on 18F-PSMA-1007 were obtained semiautomatically in dedicated software. A Spearman test was performed to explore the correlation of volumetric imaging parameters with PSA levels and Gleason score. To analyze the association between volumetric measures and PSA subgroups, we used a Kruskal-Wallis test and a Dunn's test to identify each group causing an observed difference. A total of 492 metastatic lesions were analyzed, and a significant correlation was found between wbTL-PSMA (R = 0.63, P < 0.0001) and wbPSMA-TV (R = 0.49, P < 0.0001) with serum PSA. A statistically significant difference with wbTL-PSMA was found in patients with a PSA less than or equal 0.5 ng/ml and PSA in the range of 0.51-1.0 ng/ml. 18F-PSMA-1007 PSMA volumetric parameters can provide a quantitative imaging biomarker for whole-body tumor burden.

18F-PSMA-1007 PET in Biochemical Recurrent Prostate Cancer: An Updated Meta-Analysis.

Background Prostate-specific membrane antigen- (PSMA-) targeted agents labeled with fluorine-18 (18F) have recently become available to evaluate patients with biochemical recurrent prostate cancer (BRPCa) by using positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI). We performed a systematic review and meta-analysis about the detection rate (DR) of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa patients. Methods A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through 17 May 2021 was carried out using the following search algorithm: “PSMA” AND “1007”. Only studies providing data on the DR of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa were included. A random-effects model was used to calculate the pooled DR on a per scan basis. Results Fifteen articles (853 patients) were selected and included in the systematic review, and ten were included in the quantitative analysis. Most of the studies reported a good DR of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa including also patients with low prostate-specific membrane antigen (PSA) values. The DR of 18F-PSMA-1007 PET/CT or PET/MRI was dependent on PSA serum values. The pooled DR was 81.3% (95% confidence interval: 74.6–88%) with statistical heterogeneity. A significant reporting bias (publication bias) was not detected. Conclusions 18F-PSMA-1007 PET/CT or PET/MRI showed a good DR in BRPCa patients in line with other PSMA-targeted agents. The DR of 18F-PSMA-1007 PET/CT or PET/MRI is influenced by serum PSA values. These findings should be confirmed by prospective multicentric trials.

Predictors of 18F-DCFPyL PET/CT Positivity in Patients with Biochemical Recurrence of Prostate Cancer After Local Therapy.

Our objective was to investigate the factors predicting scan positivity and disease location in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after primary local therapy using prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT. Methods: This was a 2-institution study including 245 BCR PCa patients after primary local therapy and negative results on conventional imaging. The patients underwent 18F-DCFPyL PET/CT. We tested for correlations of lesion detection rate and disease location with tumor characteristics, time from initial therapy, prostate-specific antigen (PSA) level, and PSA doubling time (PSAdt). Multivariate logistic regression analyses were used to determine predictors of a positive scan. Regression-based coefficients were used to develop nomograms predicting scan positivity and extrapelvic disease. Results: Overall, 79.2% (194/245) of patients had a positive 18F-DCFPyL PET/CT result, with detection rates of 48.2% (27/56), 74.3% (26/35), 84% (37/44), 96.7% (59/61), and 91.8% (45/49) for PSAs of <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <5.0, and ≥5.0 ng/mL, respectively. Patients with lesions confined to the pelvis had lower PSAs than those with distant sites (1.6 ± 3.5 vs. 3.0 ± 6.3 ng/mL, P < 0.001). In patients treated with prostatectomy (n = 195), 24.1% (47/195) had a negative scan result, 46.1% (90/195) showed intrapelvic disease, and 29.7% (58/195) showed extrapelvic disease. In the postradiation subgroup (n = 50), 18F-DCFPyL PET/CT was always negative at a PSA lower than 1.0 ng/mL and extrapelvic disease was seen only when PSA was greater than 2.0 ng/mL. At multivariate analysis, PSA and PSAdt were independent predictive factors of scan positivity and the presence of extrapelvic disease in postsurgical patients, with area under the curve of 78% and 76%, respectively. PSA and PSAdt were independent predictors of the presence of extrapelvic disease in the postradiation cohort, with area under the curve of 85%. Time from treatment to scan was significantly longer for prostatectomy-bed-only recurrences than for those with bone or visceral disease (6.2 ± 6.4 vs. 2.4 ± 1.3 y, P < 0.001). Conclusion:18F-DCFPyL PET/CT offers high detection rates in BCR PCa patients. PSA and PSAdt are able to predict scan positivity and disease location. Furthermore, the presence of bone or visceral lesions is associated with shorter intervals from treatment than are prostate-bed-only recurrences. These tools might guide clinicians to select the most suitable candidates for 18F-DCFPyL PET/CT imaging.