Search

Abstract Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials.

Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials. [ABSTRACT FROM AUTHOR]

Background. As artificial intelligence is expanding its applications in medicine, metabolic imaging is gaining the ability to retrieve data otherwise missed by even an experienced naked eye. Also, new radiopharmaceuticals and peptides aim to increase the specificity of positron emission tomography (PET) scans. Herein, a preliminary experience is reported regarding searching for a texture signature in routinely performed [F18]Fluciclovine imaging in prostate cancer. Materials and methods. Twenty-nine patients who underwent a PET/computed tomography (CT) scan with [18F]Fluciclovine because of biochemical prostate cancer relapse were retrospectively enrolled. First- and second-order radiomic features were manually extracted in lesions visually considered pathologic from the Local Image Features Extraction (LIFEx) platform. Statistical analysis was performed on a database of 29 lesions, one1 per patient. The dataset was split to have 20 lesions for the model training set and 9 lesions for the validation set. The Wilcoxon–Mann–Whitney test was used on the training set to select the most significant features (p-value < 0.05) predicting the dichotomous outcome in a univariate analysis. Results. The best model for predicting the outcome was found to be a multiple logistic linear regression model with two features as variables: an intensity histogram type and a gray-level size zone-based type. Conclusions. Texture analysis of [F18]Fluciclovine PET scans helps in defining prostate cancer relapse in a daily clinical setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy is a treatment option for prostate cancer patients who have increasing prostate-specific antigen values after prostatectomy. However, this treatment has never been compared directly in a single study with the course of untreated relapsed prostate cancer. We analyzed the course of prostate-specific antigen values before and after radiotherapy by calculating prostate-specific antigen doubling times. Prolongation of these values after radiotherapy indicated slower progression with this treatment. The survival analysis also suggests the advantages of salvage radiotherapy. In our analysis, when comparing our cohort with an age-matched cohort from life tables, it was observed that patients had a normal life expectancy after radiotherapy for recurrent prostate cancer following prostatectomy. In patients with prostate cancer (PCa), salvage radiotherapy (SRT) for biochemical progression (BP) after radical prostatectomy (RP) improves PCa-specific survival. However, no prospective randomized trials have compared the effect of SRT with untreated patients. In this analysis of 151 patients who received SRT for post-RP BP, we compared their overall survival (OS) with virtual, age-matched controls (n = 151,000) retrieved from government life tables. We also investigated the risk factors associated with BP and OS and compared the prostate-specific antigen (PSA) doubling times (DTs) before and after SRT for patients with BP. The median follow-up was 9.3 years for BP and 17.4 years for OS. The risk factors significantly affecting BP were Gleason score (p < 0.001), pre-SRT PSA (p = 0.003), and negative surgical margins (p = 0.003). None of these risk factors were associated with OS. In 93 patients with BP after SRT, the median PSADT was significantly prolonged compared with pre-SRT values (3.7 vs. 8.3 months, p < 0.001). The OS did not differ between patients and controls (p = 0.112), and life expectancy was similar, likely due to the survival benefit of SRT. The prolonged PSADT after SRT further supports the beneficial role of SRT in this patient population. However, subsequent treatments were not systematically recorded, which may have affected the results. [ABSTRACT FROM AUTHOR]

Between 25% and 33% of patients after radical prostatectomy experience a relapse of the disease. The risk of relapse increases in patients with risk factors up to 50%-80%. For a long time, adjuvant radiotherapy has been considered the standard of care. Four large prospective trials, that compared adjuvant and salvage radiotherapy in patients with biochemical relapse, showed the superiority of the adjuvant approach in biochemical and local relapse-free survival, but no consistent benefit in long-term endpoints (i.e., metastasis-free survival, overall survival, or carcinoma-specific survival) at the expense of increased urinary and bowel toxicity. Three large international studies comparing adjuvant and salvage radiotherapy paved the way toward early salvage radiotherapy. However, the optimal threshold of the PSA level (range of 0.2-0.5 ng/mL) for initiating early salvage radiotherapy remains unresolved and still poses a challenge in everyday clinical practice when balancing the need for early radiotherapy and the associated toxicity. Imprecise stratification of biochemical relaps patients according to the risk of clinical relapse drives efforts to find additional molecular biomarkers that would improve the timing of the salvage therapy. [ABSTRACT FROM AUTHOR]

Background. As artificial intelligence is expanding its applications in medicine, metabolic imaging is gaining the ability to retrieve data otherwise missed by even an experienced naked eye. Also, new radiopharmaceuticals and peptides aim to increase the specificity of positron emission tomography (PET) scans. Herein, a preliminary experience is reported regarding searching for a texture signature in routinely performed [F18]Fluciclovine imaging in prostate cancer. Materials and methods. Twenty-nine patients who underwent a PET/computed tomography (CT) scan with [18F]Fluciclovine because of biochemical prostate cancer relapse were retrospectively enrolled. First- and second-order radiomic features were manually extracted in lesions visually considered pathologic from the Local Image Features Extraction (LIFEx) platform. Statistical analysis was performed on a database of 29 lesions, one1 per patient. The dataset was split to have 20 lesions for the model training set and 9 lesions for the validation set. The Wilcoxon–Mann–Whitney test was used on the training set to select the most significant features (p-value < 0.05) predicting the dichotomous outcome in a univariate analysis. Results. The best model for predicting the outcome was found to be a multiple logistic linear regression model with two features as variables: an intensity histogram type and a gray-level size zone-based type. Conclusions. Texture analysis of [F18]Fluciclovine PET scans helps in defining prostate cancer relapse in a daily clinical setting.

Between 25% and 33% of patients after radical prostatectomy experience a relapse of the disease. The risk of relapse increases in patients with risk factors up to 50%–80%. For a long time, adjuvant radiotherapy has been considered the standard of care. Four large prospective trials, that compared adjuvant and salvage radiotherapy in patients with biochemical relapse, showed the superiority of the adjuvant approach in biochemical and local relapse-free survival, but no consistent benefit in long-term endpoints (i.e., metastasis-free survival, overall survival, or carcinoma-specific survival) at the expense of increased urinary and bowel toxicity. Three large international studies comparing adjuvant and salvage radiotherapy paved the way toward early salvage radiotherapy. However, the optimal threshold of the PSA level (range of 0.2–0.5 ng/mL) for initiating early salvage radiotherapy remains unresolved and still poses a challenge in everyday clinical practice when balancing the need for early radiotherapy and the associated toxicity. Imprecise stratification of biochemical relaps patients according to the risk of clinical relapse drives efforts to find additional molecular biomarkers that would improve the timing of the salvage therapy.

BackgroundWhile prostate cancer can often manifest as an indolent disease, the development of locally-advanced or metastatic disease can cause significant morbidity or mortality. Elucidation of molecular mechanisms contributing to disease progression is crucial for more accurate prognostication and effective treatments. R-Spondin 3 (RSPO3) is a protein previously implicated in the progression of colorectal and lung cancers. However, a role for RSPO3 in prostate cancer prognosis and behaviour has not been explored.MethodsWe compare the relative levels of RSPO3 expression between normal prostate tissue and prostate cancer in two independent patient cohorts (Taylor and GSE70768-Cambridge). We also examine the association of biochemical relapse with RSPO3 levels in these cohorts. For elucidation of the biological effect of RSPO3, we use siRNA technology to reduce the levels of RSPO3 in established prostate cancer cell lines, and perform in vitro proliferation, invasion, western blotting for EMT markers and clonogenic survival assays for radiation resistance. Furthermore, we show consequences of RSPO3 knockdown in an established chick chorioallantoic membrane (CAM) assay model of metastasis.ResultsRSPO3 levels are lower in prostate cancer than normal prostate, with a tendency for further loss in metastatic disease. Patients with lower RSPO3 expression have lower rates of biochemical relapse-free survival. SiRNA-mediated loss of RSPO3 results in no change to clonogenic survival and a lower proliferative rate, but increased invasiveness in vitro with induction of epithelial-mesenchymal transition (EMT) markers. Consistent with these results, lower RSPO3 expression translates to greater metastatic capacity in the CAM assay. Together, our preclinical findings identify a role of RSPO3 downregulation in prostate cancer invasiveness, and provide a potential explanation for how RSPO3 functions as a positive prognostic marker in prostate cancer.

Introduction. To date, the impact of the time interval from diagnostic prostate biopsy to radical prostatectomy on treatment outcomes remains a topical issue.Objective. To evaluate the effect of the timespan from diagnosis to radical treatment of prostate cancer (PCa) patients on tumor morphology and long-term oncological outcomes.Materials and methods. A retrospective analysis of the results of treatment of patients with high-risk PCa who underwent radical prostatectomy with extended lymphadenectomy from 2001 to 2019 in three St. Petersburg clinics was performed. The influence of the time interval from prostate biopsy to radical treatment on long-term outcomes was assessed.Results. An increase in the time interval before surgical treatment over three months did not affect the tumor morphology. Five-year biochemical relapse-free survival was 79.7%, 67.8% and 52.5% among patients with time interval from biopsy to surgical treatment less than 30 days, 30 – 90 days and more than 90 days, respectively. The time interval prior to radical treatment did not have any effect on overall and cancer-specific survival.Conclusion. The time interval from prostate biopsy to surgical intervention, not exceeding 3 months, is the most favorable with respect to long-term outcomes.

Purpose: Biochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Methods/patients: Patients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes. Results: Data from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS). Conclusion: Choline PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life. [ABSTRACT FROM AUTHOR]

PurposeBiochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Methods/patientsPatients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes.ResultsData from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS).ConclusionCholine PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life.

Background: Early diagnosis of recurrent prostate cancer is a cornerstone for further adequate therapy planning. Therefore, clinical practice and research still focuses on diagnostic tools that can detect prostate cancer in early recurrence when it is undetectable in conventional diagnostic imaging. 18F-PSMA-1007 PET/CT is a novel method to evaluate patients with biochemical recurrent PCa. The aim of this review was to evaluate the role of 18F-PSMA-1007 PET/CT in prostate cancer local recurrence, lymph node metastases and bone metastases detection. Methods: Original studies, reviews and five meta-analyses were included in this article. A total of 70 studies were retrieved, 31 were included in the study. Results: All patients described in the studies underwent 18F-PSMA-1007 PET/CT. The administered 18F-PSMA-1007 individual dose ranged from 159 ± 31 MBq to 363.93 ± 69.40 MBq. Results showed that 18F-PSMA-1007 PET/CT demonstrates a good detection rate in recurrent prostate cancer. Conclusions: 18F-PSMA-1007 PET/CT appears to achieve reliable performance in detecting recurrent prostate cancer. The high detection rate of 18F-PSMA-1007 PET/CT in recurrent prostate cancer was confirmed, especially in local recurrence and small lymph nodes with non-specific characteristics on conventional diagnostic imaging methods. However, several authors emphasize some limitations for this tracer—for example, non-specific uptake in bone lesions that can mimic bone metastases. [ABSTRACT FROM AUTHOR]

Objective: PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of 68Ga‐PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change. Patients and methods: Men with BCR who met eligibility criteria underwent 68Ga‐PSMA‐11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after 68Ga‐PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes. Results: Seventy men underwent 68Ga‐PSMA‐11 PET/CT imaging. Median age was 67 years (IQR 63–72) and median PSA was 0.48 ng/ml (IQR 0.21–1.9). PSMA‐avid disease was observed in 56% (39/70) of patients. Pre‐scan management plan was altered following scanning in 43% (30/70) of patients. Management changes were significantly more common in patients with higher baseline PSA levels (PSA≥2 ng/ml, p = 0.01). 18/36 (50%) of the patients initially planned for watchful waiting had their management changed, including the use of salvage pelvic radiotherapy (n = 7) and stereotactic ablative body radiotherapy to oligometastatic disease (n = 6). Conclusion: Management change after 68Ga‐PSMA PET/CT for BCR is common and typically resulted in treatment intensification strategies in those planned for a watchful waiting approach. This study adds to the growing pool of evidence supporting the clinical utility of PSMA PET/CT imaging in the care of patients with BCR after definitive therapy. [ABSTRACT FROM AUTHOR]

Stefanos Kachris,1 Chara Papadaki,2 Konstantinos Rounis,3 Eliza Tsitoura,4 Chrysanthi Kokkinaki,4 Christoforos Nikolaou,5– 7 George Sourvinos,4 Dimitrios Mavroudis2,3 1Department of Radiation Oncology, University General Hospital, Heraklion, Crete, Greece; 2Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece; 3Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece; 4Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, Crete, Greece; 5Department of Biology, University of Crete, Heraklion, Crete, Greece; 6Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology (FORTH), Heraklion, Crete, Greece; 7Institute of Bioinnovation, Biomedical Science Research Center “Alexander Fleming”, Athens, GreeceCorrespondence: Dimitrios MavroudisLaboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, 71110, GreeceTel +30 2810392750Email mavroudis@uoc.grIntroduction: Disease recurrence is a major concern in patients with localized prostate cancer (PCa) following treatment with radiotherapy (RT), and few studies have evaluated the clinical relevance of microRNAs (miRNAs) prior and post-RT.Purpose: We aimed to investigate the significance of miRNAs in the outcomes of prostate cancer patients undergoing radiotherapy and to identify the related pathways through bioinformatics analysis.Materials and Methods: The expression levels of miR-21, miR-106b, miR-141 and miR-375 involved in the response to radiotherapy were assessed by RT-qPCR in the serum of PCa patients (n=56) prior- and post-RT.Results: Low expression levels of miR-106b prior-RT were associated with extracapsular extension and seminal vesicles invasion by the tumor (p=0.031 and 0.044, respectively). In the high-risk subgroup (n=47), post-RT expression levels of miR-21 were higher in patients with biochemical relapse (BR) compared to non-relapse (p=0.043). Also, in the salvage treatment subgroup (post-operative BR; n=20), post-RT expression levels of miR-21 and miR-106b were higher in patients with BR compared to non-relapse (p=0.043 and p=0.032, respectively). In the whole group of patients, high expression levels of miR-21 prior-RT and of miR-106b post-RT were associated with significantly shorter overall survival (OS; p=0.049 and p=0.050, respectively). No associations were observed among miR-141 and miR-375 expression levels with clinicopathological features or treatment outcome. Bioinformatics analysis revealed significant enrichment in DNA damage response pathways.Conclusion: Circulating miRNAs prior or post-RT may hold prognostic implications in patients with PCa.Keywords: prostate cancer, radiotherapy, salvage radiotherapy, circulating microRNAs, high risk, biochemical relapse

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. [ABSTRACT FROM AUTHOR]

Abstract Background Biochemical recurrence is defined as only rising CA-125 but no radiographic evidence of disease; noteworthily, it generally precedes the onset of clinical evidence. Now treatment strategies of biochemical recurrence ovarian cancer (OC) remain controversial. Apatinib as monotherapy or in combination with other chemotherapeutic agents has shown its effect in the treatment of some advanced malignancies. In our study, we focused on the efficacy of apatinib in recurrent OC, especially its clinical activity in biochemical-only recurrent OC patients. Methods We retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan–Meier method. Results All patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43–8.57). And in patients with biochemical-only relapse, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%. Conclusions Apatinib is a well-tolerated and effective agent to delay clinical progression of patients with biochemical-only recurrent OC. More important, our study shows the promising prospect for treating OC patients with asymptomatic biochemical relapse.

Background: Biochemical recurrence is defined as only rising CA-125 but no radiographic evidence of disease; noteworthily, it generally precedes the onset of clinical evidence. Now treatment strategies of biochemical recurrence ovarian cancer (OC) remain controversial. Apatinib as monotherapy or in combination with other chemotherapeutic agents has shown its effect in the treatment of some advanced malignancies. In our study, we focused on the efficacy of apatinib in recurrent OC, especially its clinical activity in biochemical-only recurrent OC patients. Methods: We retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan–Meier method. Results: All patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43–8.57). And in patients with biochemical-only relapse, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%. Conclusions: Apatinib is a well-tolerated and effective agent to delay clinical progression of patients with biochemical-only recurrent OC. More important, our study shows the promising prospect for treating OC patients with asymptomatic biochemical relapse. [ABSTRACT FROM AUTHOR]

Background: Studies of microRNAs (miRNAs) and genes have particular interest for cancer biology and medicine due to the discovery of new therapeutic targets and markers. These studies are extensively influenced by anticancer therapy, as miRNAs interfere with the therapy's efficacy in prostate cancer (PCa). Objectives: In this article, we summarise the available data on the influence of radical prostatectomy (RP) and biochemical recurrence on miRNA expression. Materials and methods: Molecular targets of these miRNAs, as well as the reciprocal relations between different miRNAs and their targets, were studied using the DIANA, STRING and TransmiR databases. Special attention was dedicated to the mechanisms of PCa development, miRNA, and associated genes as tumour development mediators. Results and discussion: Combined analysis of the databases and available literature indicates that expression of four miRNAs that are associated with prostate cancer relapse and alter their expression after RP, combined with genes that closely interact with selected miRNAs, has high potential for the prediction of PCa relapse after RP. PCa tissues and biofluids, both immediately after RP for diagnostics/prognostics and in long‐term (relapse) monitoring, may be used as sources of these miRNAs. Conclusion: An overview of the usefulness of published data and bioinformatics resources looking for diagnostic markers and molecular targets is presented in this article. The selected miRNA and gene panels have good potential as prognostic and PCa relapse markers after RP and likely could also serve as markers for therapeutic efficiency on a broader scale. [ABSTRACT FROM AUTHOR]

Kachris S, Papadaki C, Rounis K, et al. Cancer Manag Res. 2021;13:8257–8271. The authors have advised there is an error with the author list on page 8257. The author “Stefanos Kachris1” should read “Stefanos Kachris1,2”. The authors apologize for this error. Read the original article

Abstract Background Adjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome. Methods We evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42–85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level

Abstract Background While prostate cancer can often manifest as an indolent disease, the development of locally-advanced or metastatic disease can cause significant morbidity or mortality. Elucidation of molecular mechanisms contributing to disease progression is crucial for more accurate prognostication and effective treatments. R-Spondin 3 (RSPO3) is a protein previously implicated in the progression of colorectal and lung cancers. However, a role for RSPO3 in prostate cancer prognosis and behaviour has not been explored. Methods We compare the relative levels of RSPO3 expression between normal prostate tissue and prostate cancer in two independent patient cohorts (Taylor and GSE70768—Cambridge). We also examine the association of biochemical relapse with RSPO3 levels in these cohorts. For elucidation of the biological effect of RSPO3, we use siRNA technology to reduce the levels of RSPO3 in established prostate cancer cell lines, and perform in vitro proliferation, invasion, western blotting for EMT markers and clonogenic survival assays for radiation resistance. Furthermore, we show consequences of RSPO3 knockdown in an established chick chorioallantoic membrane (CAM) assay model of metastasis. Results RSPO3 levels are lower in prostate cancer than normal prostate, with a tendency for further loss in metastatic disease. Patients with lower RSPO3 expression have lower rates of biochemical relapse-free survival. SiRNA-mediated loss of RSPO3 results in no change to clonogenic survival and a lower proliferative rate, but increased invasiveness in vitro with induction of epithelial–mesenchymal transition (EMT) markers. Consistent with these results, lower RSPO3 expression translates to greater metastatic capacity in the CAM assay. Together, our preclinical findings identify a role of RSPO3 downregulation in prostate cancer invasiveness, and provide a potential explanation for how RSPO3 functions as a positive prognostic marker in prostate cancer.

Several classes of concomitant medications have been shown to affect oncological outcomes in patients with prostate cancer (PCa). We assessed the association between the use of commonly prescribed concomitant medications and biochemical relapse-free survival (bRFS) in patients with localised PCa treated with radiotherapy and androgen deprivation therapy (ADT). A secondary pooled analysis of two phase III randomised trials was carried out. In the first trial, patients with localised PCa with clinical stage T1b-T3, prostate-specific antigen <30 ng/ml and Gleason score ≤7 were treated with radical radiotherapy and 6 months of ADT starting 4 months before or concomitantly with radiotherapy. In the second trial, patients with high-risk PCa were treated with radical radiotherapy and 36 months of ADT with randomisation to three-dimensional conformal or intensity-modulated radiotherapy. Information on concomitant medications was collected from the medical record. Univariable and multivariable Cox regression was used to identify factors associated with bRFS. Overall, 486 patients were evaluable. The median follow-up was 125 months; 10-year bRFS was 83.7%. On univariable analysis, receipt of metformin was significantly associated with worse bRFS. Ten-year bRFS was 73% and 85% for patients with and without concomitant metformin (adjusted hazard ratio 2.11, 95% confidence interval 1.03–4.33). Similar evidence of an association was observed with sulfonamide-based α1-receptor blockers (adjusted hazard ratio 2.72, 95% confidence interval 1.31–5.66). However, no such association was seen with receipt of quinazoline-based α1-receptor blockers (adjusted hazard ratio 1.09, 95% confidence interval 0.42–2.82). There was no significant association between bRFS and receipt of all other medication classes considered. In this population of patients with localised PCa treated with radiotherapy and ADT, receipt of concomitant metformin and sulfonamide-based α1-receptor blockers was associated with inferior biochemical outcome. Randomised trials are required to assess the true effect of these medications on oncological outcomes in localised PCa. • Concomitant metformin was associated with poorer biochemical control following radiotherapy and androgen deprivation. • This is directionally opposite to prior studies showing superior prostate cancer outcomes in patients receiving metformin. • Receipt of sulfonamide-based α1-receptor blockers was also associated with inferior biochemical outcome in this cohort. [ABSTRACT FROM AUTHOR]

Prezentujeme kazuistiku pacienta s biochemickým relapsem po radikální prostatektomii, který byl vyšetřen pomocí PET/CT s radiofarmakem 18F-fluciklovin. We present a case report of a patient with biochemical relapse following radical prostatectomy, who was examined by PET/CT with radiopharmaceutical 18F-fluciclovine. [ABSTRACT FROM AUTHOR]

Background: The sensitivity and specificity of bone scintigraphy and thoraco-abdominopelvic CT scans traditionally used for the staging of prostate cancer don’t meet clinical requirements. In 2020 18F-JK-PSMA-7 positron emission tomography-computed tomography (PET-CT) became available in our country for routine clinical diagnostics. Methods: As part of our self-assessment, we retrospectively analysed the results of 24 PSMA PET-CTs realised for our patients up to 31 December 2020. Results: The indication of the examination was biochemical recurrence after radical prostatectomy (prostate specific antigen (PSA) >0.2 ng/mL) for 16 patients and primary staging (PSA range: 5.2–70 ng/mL) for 8 patients. Biochemical recurrence was related to local relapse in 2 cases, regional lymph node involvement in 5 cases, oligo- and multi-metastatic spread in 1 and 3 cases respectively. 5 patients had no detectable lesion. Patients with PSA

The biochemical relapse of prostate cancer is diagnostically challenging but of high clinical impact for subsequent patient treatment. PET/CT with radiolabeled PSMA ligands outperforms conventional diagnostic methods in the detection of tumor recurrence. Several radiopharmaceuticals were and are available for use. The aim of this study was to investigate whether the routinely applied [68Ga]Ga-PSMA ligands PSMA-617, -I&T and -11 (HBED-CC) differ in physiological and pathological distribution, or in tumor detection rate. A retrospective evaluation of 190 patients (39 patients received PSMA-617, 68 patients PSMA-I&T and 83 patients PSMA-11) showed significant differences in tracer accumulation within all organs examined. The low retention within the compartments blood pool, bone and muscle tissue is a theoretical advantage of PSMA-11. Evaluation of tumor lesion uptake and detection rate did not reveal superiority of one of the three radiopharmaceuticals, neither in the whole population, nor in particularly challenging subgroups like patients with very low PSA levels. We conclude that all three [68Ga]Ga-PSMA ligands are equally feasible in this clinically important scenario, and may replace each other in case of unavailability or production restrictions.

The treatment of local prostate cancer recurrence after cryotherapy is challenging since the optimal management is unknown. We collected the available evidence to date to better define the risk and benefit of salvage radiotherapy (SRT) after cryotherapy failure for localized prostate cancer. This review confirms the feasibility of SRT in terms of biochemical control and late toxicity rate. However, the absence of comparative trials or prospective studies, coupled with the heterogeneity of patients treated and the variations in treatments delivered across the analyzed studies, highlights the need for cautious consideration when opting for salvage radiotherapy. Therefore, we highly recommend the inclusion of patients in dedicated clinical trials to comprehensively assess the efficacy and safety of this approach. [Display omitted] • Our review investigated salvage radiotherapy in prostate cancer patients. • Who had received prior cryotherapy and experienced local relapse. • Finding suggests feasible approach with acceptable toxicities. [ABSTRACT FROM AUTHOR]

Abstract Purpose 11C–choline PET/CT is a widely-used tool for the diagnostic of prostate cancer (PCa). In literature, a great variability of local relapse (LR) detection rate is reported. The aim of this study is to provide positivity criteria for 11C–choline PET/CT detection of LR in patients who had surgery for PCa and presented prostate specific antigen (PSA) failure. Methods Sixty patients radically treated for PCa and presenting PSA failure were retrospectively analysed. Two Nuclear Medicine Physicians revised the 11C–choline PET/CT scans and defined by consensus if even mild focal uptake was present in the prostate bed (PB) and bladder-urethral junction (BUJ) along midline, regardless the previous report results. The results were subsequently correlated with a clinical and radiological follow up (FU) of 1 to 2 year and with TNM staging, Gleason score (GS), PSA level at relapse, radiotherapy (RT) and hormone therapy (HT) after surgery. Results There was focal uptake in 22/60 patients; 11 of them were true positive and 11 false positive. The PSA level showed a tight connection with the true positivity/negativity of Choline scan. Most of true positive cases (10/11 patients) presented a PSA ≥ 1 ng/ml, while approximately half of the false positive cases (5/11 patients) presented PSA below 1 ng/ml. The other variables were not correlated to Choline detection rate for LR. Conclusions This study shows that an even mild focal uptake of Choline in the PB and BUJ along midline must be considered suspicious for LR in patients radically treated for PCa, especially if they are presenting with PSA level > 1 ng/ml.

Background: Adjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome.Methods: We evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42-85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level <0.1 ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5 months (range 1.4-128.0 months).Results: Early SRT at PSA levels <0.3 ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14-0.75, p = 0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02-1.44, p = 0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02-1.79, p = 0.15).Conclusion: For patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3 ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients' postoperative clinical condition.Study Registration: The present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate if prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has a higher detection rate compared to standard contrast CT imaging for patients with a rising prostate-specific antigen (PSA) following definitive treatment (i.e., curative radical prostatectomy, radiotherapy, and brachytherapy) for prostate cancer in a private hospital setting. A retrospective single-site clinical audit was conducted on 150 PSMA PET/CT scans done for patients with a rising PSA after definitive treatment for prostate cancer. All studies were performed using I and T Ga-68 PSMA produced on a Scintomics radiopharmaceutical unit (Munich). All scans were performed on a GE 710 PET/CT scanner. All studies were compared to standard CT and other imaging. Of the 150 patients who had a 68Gallium (Ga)-PSMA PET/CT for a rise in their PSA levels, 102/150 (68%) of patients had PSMA-avid scans compared to the conventional imaging group which had an overall detection rate of 42% (63/150). The rates of detection were 100%, 90%, 92%, 67%, and 25% at PSA levels of >10 μg/L, 5–10 μg/L, >1.5 μg/L, 0.5–1.5 μg/L, and <0.5 μg/L, respectively. PSMA PET/CT also solely picked up 39/102 (38%) of prostate cancer relapses compared to the conventional imaging group. In our study of 150 patients with biochemical recurrence of prostate cancer, 68Ga-PSMA PET/CT demonstrated a superior detection rate (P < 0.05) compared to conventional imaging, including patients with low PSA levels (<0.5 μg/L). [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant radiotherapy (ART) for biochemical relapse (BR) after radical prostatectomy (RP) showed increased disease-free survival (DFS) in three previous randomized trials. Retrospective phase II trials evaluated if early salvage RT (ESRT) is equivalent to ART. Our study aims to compare ART and ESRT to salvage RT.Materials and methods: We compared RP plus ART and ESRT versus SRT. Indication for RT was made by PSA determination after RP: ART when PSA ≤ 0.2 ng/ml, ESRT when PSA ≤ 0.3 after PSA rise from 0.0 to SRT PSA ≥ 0.3. The cause of death of each patients was analyzed, DFS, cause-specific survival (CSS) overall survival (OS) and metastasis-free survival (MFS) in relation to RT intention.Results: Between 1993 and 2008, 204 patients with a median age of 65 years (44-75) were treated. The median follow-up was 160 months (28.1-273.3). At diagnosis, 89.7% had localized clinical stages and 90.2% had Gleason (G) ≤ 7. The median PSA was 10 (range 4-101). The postoperative G was ≥ 7 in 66.2%; 56.4% had ≥ 2 positive margins; 29.4% received ART, 20% ESRT and 59.3% SRT. The DFS for ART, ESRT and SRT was 74, 56 and 39% with significant differences between the three groups (p < 0.001). ART + ESRT were combined versus SRT; for the DFS, the significant differences (p < 0.001) remained 67% versus 39%. Positive margins, pT3 and pre-RT PSA were significant factors on multivariate analysis. The CSS in the ART + ESRT group was 92 vs. 78% in the SRT group (p < 0.05). OS was 69% in ART + ESRT vs. 57% in SRT (p < 0.05). MFS was 82.7% in ART + ESRT vs. 67.4% in SRT.Conclusions: In this study the ART + ESRT presented benefits versus SRT in DFS, CSS, OS and MFS. [ABSTRACT FROM AUTHOR]

Resumen Antecedentes y objetivos Comparar prospectivamente la tasa de detección de la PET/TC con 68Ga-DOTATATE versus 11C-colina en pacientes con cáncer de próstata en recaída bioquímica y evaluar in vivo la expresión de receptores de la somatostatina con el fin de planificar terapias dirigidas (177Lu-DOTATATE). Material y métodos Analizamos prospectivamente 64 pacientes con recaída bioquímica (mediana PSA: 4,25 ng/mL). Se realizó una PET/TC con 11C-colina y otra con 68Ga-DOTATATE. Se midió el SUVmáx en todas las lesiones. Se consideraron como patrón de referencia las imágenes correlativas, histopatología y/o seguimiento clínico y bioquímico. Resultados La tasa de detección global por paciente fue del 48,43% para 68Ga-DOTATATE y de 46,87% para 11C-colina. Los resultados fueron concordantes en 53 casos (82,81%). El SUV máximo de la 11C-colina fue significativamente mayor que el correspondiente al 68Ga-DOTATATE para todas las lesiones concordantes (n = 130): 6,17 (1,7-15,5) versus 4,38 (1,37-26,7), mediana (rango), para cada radiotrazador, respectivamente (P < 0,0001). Los valores por paciente de sensibilidad y especificidad fueron los mismos para ambas técnicas: 0,82 (0,65-0,93) y 0,9 (0,73-0,98), respectivamente. Aunque la diferencia no fue estadísticamente significativa, la sensibilidad fue menor para pacientes con niveles de PSA inferiores: 0,63 vs. 0,89; p = 0,13. Se encontró una correlación significativa entre el SUVmáx de ambos trazadores (r = 0,41, n = 130, p < 0,0001). Conclusiones La PET/TC con 68Ga-DOTATATE y la PET/TC con 11C-colina parecen poseer alta capacidad de detección de lesiones patológicas en la evaluación de los pacientes con cáncer de próstata en recaída bioquímica. Se necesitan más estudios con el fin de probar el posible valor clínico complementario de estas técnicas PET/TC, y para el 68Ga-DOTATATE para la potencial planificación de terapias mediadas por los receptores de somatostatina (177Lu-DOTATATE). Abstract Background and objectives To prospectively compare the detection rate of 68Ga-DOTATATE versus 11C-choline PET/CT in patients with prostate cancer in biochemical relapse, and to evaluate somatostatin receptor expression in vivo to plan targeted therapies (177Lu-DOTATATE). Material and methods We prospectively analysed 64 patients with biochemical relapse (median PSA: 4.25 ng/mL). A PET/CT was performed with 11C-choline, and another with 68Ga-DOTATATE. The SUVmax was measured in all lesions. The correlative images, histopathology and/or clinical and biochemical follow-up were taken as the reference standard. Results The overall detection rate per patient was 48.43% for 68Ga-DOTATATE and 46.87% for 11C-choline. The results were concordant in 53 cases (82.81%). The maximum SUV of 11C-choline was significantly higher than that of 68Ga-DOTATATE for all the concordant lesions (n=130): 6.17 (1.7-15.5) versus 4.38 (1.37-26.7), median (range) for each radiotracer, respectively (p <.0001). The sensitivity and specificity values per patient were the same for both techniques: 0.82 (0.65-0.93) and 0.9 (0.73-0.98), respectively. Although the difference was not significant, the sensitivity was lower in patients with lower PSA levels: 0.63 vs. 0.89; p =.13. A significant correlation was found between the SUVmax of both tracers (r = 0.41, n = 130, p <.0001). Conclusions 68Ga-DOTATATE PET/CT and 11C-choline PET/CT seem to have a high capacity to detect pathological lesions in the assessment of patients with prostate cancer with biochemical relapse. Further studies are required to test the potential complementary value of these PET/CT techniques, and to evaluate the potential role of 8Ga-DOTATATE for planning somostatin receptor-mediated therapies (177Lu-DOTATATE). [ABSTRACT FROM AUTHOR]

Background: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. Interpretation: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Background: Ultrasensitive imaging has been demonstrated to influence biochemical relapse treatment. PSICHE is a multicentric prospective study, aimed at exploring detection rate with 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and outcomes with a predefined treatment algorithm tailored to the imaging., Methods: Patients affected by biochemical recurrence after surgery (prostate specific antigen [PSA] > 0.2 < 1 ng/mL) underwent staging with 68Ga-PSMA PET/CT. Management followed this treatment algorithm accordingly with PSMA results: prostate bed salvage radiotherapy (SRT) if negative or positive within prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease, androgen deprivation therapy (ADT) if nonoligometastatic disease. Chi-square test was used to evaluate the relationship between baseline features and rate of positive PSMA PET/CT., Results: One hundred patients were enrolled. PSMA results were negative/positive in the prostate bed in 72 patients, pelvic nodal or extrapelvic metastatic disease were detected in 23 and 5 patients. Twenty-one patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Fifty patients were treated with prostate bed SRT, 23 patients underwent SBRT to pelvic nodal disease, five patients were treated with SBRT to oligometastatic disease. One patient underwent ADT. NCCN high-risk features, stage > pT3 and ISUP score >3 reported a significantly higher rate of positive PSMA PET/CT after restaging (p = 0.01, p = 0.02, and p = 0.002). By quartiles of PSA, rate of positive PSMA PET/CT was 26.9% (>0.2; <0.29 ng/mL), 24% (>0.3; <0.37 ng/mL), 26.9% (>0.38; <0.51 ng/mL), and 34.7% (>0. 52; <0.98 ng/mL)., Conclusions: PSICHE trial constitute a useful platform to collect data within a clinical framework where modern imaging and metastasis-directed therapy are integrated., (© 2023 Wiley Periodicals LLC.)

Purpose: The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially 68Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). 18F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced 18F-PSMA-1007 in patients with recurrent PCa.Methods: This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq 18F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a 18F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.Results: Of the 100 patients, 95 (95%) showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04-41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5-10). The majority of patients (70) with a GS available had a score in the range 7-9. The rate of pathological scans in these patients was 93% (65/70). The median SUVmax values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and >2.0 ng/ml, respectively. The median SUVmax in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.Conclusion: 18F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological 18F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients. [ABSTRACT FROM AUTHOR]

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. Methods: This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. Results: The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. Conclusion: The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Introduction: The classification of patients with prostate cancer is used to determine treatments based on risk factors. The presence of secondary circulating prostate tumour cells (CPCs) detected in peripheral blood after a curative treatment has been associated with a worse prognosis. We present a prospective study of CPC detection post radiotherapy and the oncological results. Patients and methods: All of the patients classified as low and intermediate risk that were treated with radiotherapy were included. Three months after finishing treatment, an 8-ml blood sample was taken to detect CPCs. Mononuclear cells were obtained using gel centrifugation, and CPCs were identified using immunocytochemistry with anti-prostate-specific antigen. Patients were classified as low-risk CPC positive or negative and intermediate-risk CPC positive or negative. The biochemical relapse-free survival analysis was determined based on a follow-up of up to 15 years using the Kaplan-Meier and Cox regression models. Biochemical failure was defined according to the Pheonix II criteria. Results: Of 241 patients, 181 (75.1%) were classified as low risk and 60 (24.9%) as intermediate risk. Biochemical failure was observed in 27.1% (49/181) of the low-risk prostate cancer participants and in 53.3% (32/60) of intermediate-risk participants after 15 years of follow-up. 20.4% (37/181) of the low-risk cancer participants had detectable CPCs in comparison with 43.3% (26/60) of the intermediate-risk cancer participants (p < 0.001 overall risk 2.98, confidence interval (CI) 95% 1.59-5.56; relative risk 2.12, CI 95% 1.41-3.19). Positive CPC patients had a worse prognosis, and a shorter time period until biochemical relapse, regardless of risk group. The biochemical relapse-free survival curves show that intermediate-risk participants who were CPC negative had a higher survival rate and slower disease progression than those participants who were low risk but CPC positive. Conclusions: CPC detection is a risk factor for biochemical relapse and could be useful in identifying patients that will need additional treatment. [ABSTRACT FROM AUTHOR]

Resumen Objetivo La PET/TC con 11 C-colina ha mostrado buenos resultados en la reestadificación del cáncer de próstata (CP) con antígeno específico prostático (PSA) elevado. Su uso con niveles bajos es controvertido. Nuestro objetivo fue evaluar la aportación de la 11 C-colina PET/TC en pacientes con CP, recidiva bioquímica y PSA < 1 ng/ml. Material y método Se evaluaron retrospectivamente 50 pacientes consecutivos (edad: 65,9 ± 5,6 años) con recidiva bioquímica de CP y PSA < 1 ng/ml (media: 0,4 ± 0,2). La PET/TC fue adquirida a los 20 min de la administración intravenosa de 555-740 MBq de 11 C-colina. El seguimiento mínimo fue de 30 meses. Resultados De los 50 pacientes, 21 (42%) mostraron una 11 C-colina PET/TC anormal. En 7 (14%) se confirmó la afectación tumoral (4 en lecho prostático, 4 en ganglios pélvicos, 2 en ganglios mediastínicos y un tumor síncrono sigmoide) y se modificó en todos ellos el tratamiento inicialmente previsto. En 2 pacientes (4%) se confirmó enfermedad benigna (uno con sarcoidosis, otro con secuelas de TBC) y en 3 pacientes (6%) ausencia de enfermedad. En los otros 9 pacientes (18%) los hallazgos no fueron estudiados (7 en ganglios mediastínicos y 4 en pélvicos). La 11 C-colina PET/TC fue normal en 29 pacientes (58%). Solo en 2 de ellos se confirmó recidiva a los 30 meses. Conclusión La 11 C-colina PET/TC demostró su utilidad en la recidiva bioquímica de CP y PSA < 1 ng/ml en el 14% de los pacientes al mostrar enfermedad tumoral, lo que tuvo implicaciones terapéuticas. En un 4% se detectó enfermedad benigna. Una 11 C-colina PET/TC normal se asoció a una tasa de recurrencia muy baja a los 30 meses. Objective 11 C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11 C-choline PET/CT in patients with PCa, biochemical relapse and PSA < 1 ng/ml. Material and method Fifty consecutive patients (mean age: 65.9 ±5.6 years) with biochemical relapse of PCa and serum PSA < 1 ng/ml were evaluated retrospectively. PET/CT was performed 20 min after intravenous administration of 555-740 MBq of 11 C-choline. Minimum follow up time was 30 months. Results Twenty-one out of 50 patients (42%) had an abnormal 11 C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. Conclusions 11 C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA < 1 ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11 C-choline PET/CT was associated with a very low rate of recurrence at 30 months. [ABSTRACT FROM AUTHOR]

Aims Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. Materials and methods Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03. Results All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60–80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of –77.1% (14.3–99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0–2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis ( P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation ( P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity. Conclusion Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control. [ABSTRACT FROM AUTHOR]

Purpose of Review: Bladder neck preservation (BNP) during radical prostatectomy (RP) has been proposed as a method to improve early recovery of urinary continence after radical prostatectomy. However, there is concern over a possible increase in the risk of positive surgical margins and prostate cancer recurrence rate. A recent systematic review and meta-analysis reported improved early recovery and overall long-term urinary continence without compromising oncologic control. The aim of our study was to perform a critical review of the literature to assess the impact on bladder neck and base margins after bladder neck sparing radical prostatectomy. Evidence Acquisition: We carried out a systematic review of the literature using Pubmed, Scopus and Cochrane library databases in May 2017 using medical subject headings and free-text protocol according to PRISMA guidelines. We used the following search terms: bladder neck preservation, prostate cancer, radical prostatectomy and surgical margins. Studies focusing on positive surgical margins (PSM) in bladder neck sparing RP pertinent to the objective of this review were included. Evidence Synthesis: Overall, we found 15 relevant studies reporting overall and site-specific positive surgical margins rate after bladder neck sparing radical prostatectomy. This included two RCTs, seven prospective comparative studies, two retrospective comparative studies and four case series. All studies were published between 1993 and 2015 with sample sizes ranging between 50 and 1067. Surgical approaches included open, laparoscopic and robot-assisted radical prostatectomy. The overall and base-specific PSM rates ranged between 7-36% and 0-16.3%, respectively. Mean base PSM was 4.9% in those patients where bladder neck sparing was performed, but only 1.85% in those without sparing. Summary: Bladder neck preservation during radical prostatectomy may increase base-positive margins. Further studies are needed to better investigate the impact of this technique on oncological outcomes. A future paradigm could include modification of intended approach to bladder neck dissection when anterior base lesions are identified on pre-operative MRI. [ABSTRACT FROM AUTHOR]

BackgroundOur previous work on early PSA kinetics following prostate stereotactic body radiation therapy (SBRT) demonstrated that an initial rapid and then slow PSA decline may result in very low PSA nadirs. This retrospective study sought to evaluate the PSA nadir 5 years following SBRT for low- and intermediate-risk prostate cancer (PCa).Methods65 low- and 80 intermediate-risk PCa patients were treated definitively with SBRT to 35–37.5 Gy in 5 fractions at Georgetown University Hospital between January 2008 and October 2011. Patients who received androgen deprivation therapy were excluded from this study. Biochemical relapse was defined as a PSA rise >2 ng/ml above the nadir and analyzed using the Kaplan–Meier method. The PSA nadir was defined as the lowest PSA value prior to biochemical relapse or as the lowest value recorded during follow-up. Prostate ablation was defined as a PSA nadir