Papers by phillip stricker
The Journal of Nuclear Medicine, Jul 26, 2017
See an invited perspective on this article on page 1969. 68 Ga-PSMA (prostate-specific membrane a... more See an invited perspective on this article on page 1969. 68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA # 0.1 ng/mL and .50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% (n 5 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% (n 5 71/99). Forty-five percent (n 5 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% (n 5 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% (n 5 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n 5 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy.
Cancers, 2020
The prostate is surrounded by periprostatic adipose tissue (PPAT), the thickness of which has bee... more The prostate is surrounded by periprostatic adipose tissue (PPAT), the thickness of which has been associated with more aggressive prostate cancer (PCa). There are limited data regarding the functional characteristics of PPAT, how it compares to subcutaneous adipose tissue (SAT), and whether in a setting of localized PCa, these traits are altered by obesity or disease aggressiveness. PPAT and SAT were collected from 60 men (age: 42–78 years, BMI: 21.3–35.6 kg/m2) undergoing total prostatectomy for PCa. Compared to SAT, adipocytes in PPAT were smaller, had the same basal rates of fatty acid release (lipolysis) yet released less polyunsaturated fatty acid species, and were more sensitive to isoproterenol-stimulated lipolysis. Basal lipolysis of PPAT was increased in men diagnosed with less aggressive PCa (Gleason score (GS) ≤ 3 + 4) compared to men with more aggressive PCa (GS ≥ 4 + 3) but no other measured adipocyte parameters related to PCa aggressiveness. Likewise, there was no dif...
Jesse Ende1,4; Amer Amin2,3,4; Gemma Sheehan-Dare1; Thomas Cusick2; Bao Ho1; Joanne Keane1; Andre... more Jesse Ende1,4; Amer Amin2,3,4; Gemma Sheehan-Dare1; Thomas Cusick2; Bao Ho1; Joanne Keane1; Andrew Nguyen1; Victor Liu1; Jonathan Lee1; Lyn Chan1; Peter Lin4,5,6; Andrew Chen1; Karen Fullard1; Phillip Stricker2,4; Louise Emmett1,4* 1Nuclear Medicine Department, St Vincent’s Hospital Sydney, Sydney, Australia. 2St Vincent’s Prostate Cancer Centre, Sydney, Australia. 3Garvan Institute of Medical Research, Sydney, Australia. 4School of Medicine, University of New South Wales, Sydney, Australia. 5Department of Nuclear Medicine and PET, Liverpool Hospital Sydney, Sydney, Australia. 6School of Medicine, Western Sydney University, Sydney, Australia.
eBioMedicine, 2021
Background: Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20À3... more Background: Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20À30% of men with metastatic castration-resistant prostate cancer (mCRPC). Ceramide metabolism may have a role in ARSI resistance. Our study's aim is to investigate the association of the ceramide-sphingosine-1-phosphate (ceramide-S1P) signalling axis with ARSI resistance in mCRPC. Methods: Lipidomic analysis (»700 lipids) was performed on plasma collected from 132 men with mCRPC, before commencing enzalutamide or abiraterone. AR gene aberrations in 77 of these men were identified by deep sequencing of circulating tumour DNA. Associations between circulating lipids, radiological progression-free survival (rPFS) and overall survival (OS) were examined by Cox regression. Inhibition of ceramide-S1P signalling with sphingosine kinase (SPHK) inhibitors (PF-543 and ABC294640) on enzalutamide efficacy was investigated with in vitro assays, and transcriptomic and lipidomic analyses of prostate cancer (PC) cell lines (LNCaP, C42B, 22Rv1). Findings: Men with elevated circulating ceramide levels had shorter rPFS (HR=2¢3, 95% CI=1¢5À3¢6, p = 0¢0004) and shorter OS (HR=2¢3, 95% CI=1¢4À36, p = 0¢0005). The combined presence of an AR aberration with elevated ceramide levels conferred a worse prognosis than the presence of only one or none of these characteristics (median rPFS time = 3¢9 vs 8¢3 vs 17¢7 months; median OS time = 8¢9 vs 19¢8 vs 34¢4 months). SPHK inhibitors enhanced enzalutamide efficacy in PC cell lines. Transcriptomic and lipidomic analyses
Cancers, 2020
Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as ... more Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D’Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) hi...
Journal of Nuclear Medicine, 2019
Background 68 Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR)... more Background 68 Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results The median PSA was 0.26ng/mL (IQR 0.15-0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p<0.0001). On logistic regression PSMA was more independently predictive of FFP than established clinical predictors, including PSA, T-stage, surgical margin status or Gleason score (p < 0.002). 32% of men with a negative PSMA PET did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59ng/mL over the 3 years. Conclusion: PSMA PET result is highly predictive of FFP at 3 years in men undergoing sRT for BCR following RP. In particular, men with negative PSMA PET or disease identified as still confined to the prostate fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional ADT than those with extra fossa disease.
European Urology, 2019
Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient... more Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised. Objective: To develop consensus statements for all domains of DAT. Design, setting, and participants: A protocol-driven, three phase study was undertaken by the
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Tijdschrift voor Urologie, 2018
Samenvatting Deze studie toont de uitkomsten van [ 68 Ga]PSMA-PET/CT-gestuurde salvagetherapie bi... more Samenvatting Deze studie toont de uitkomsten van [ 68 Ga]PSMA-PET/CT-gestuurde salvagetherapie bij mannen (n = 142) na radicale prostatectomie (RP) met een stijging van het prostaatspecifiek antigeen (PSA; 0,05-0,5 ng/ml). De [ 68 Ga]PSMA-PET/CT-scan was positief voor tumoractiviteit bij 84 mannen (36: prostaatfossa; 31: pelviene lymfeklieren ± prostaatfossa; 17: metastase op afstand). N = 88 ondergingen een salvagebehandeling (med. follow-up 12,5 mnd). Er was een PSA-respons (PSA < 0,01 of reductie >75 % in laatste PSA na salvagebehandeling) bij 69,3 % van de mannen (83 % met een negatieve PET/CT, 81 % met een positieve PET/CT in de prostaatfossa na radiotherapie op de fossa en 48,5 % bij een PET/CT die verdacht was voor een metastase in de pelviene lymfeklieren). [ 68 Ga]PSMA-PET/CT-imaging is instaat om patiënten met een biochemisch recidief na RP te identificeren die beter reageren op salvagetherapie. Trefwoorden prostaatkanker • [ 68 Ga]PSMA-PET/CT • salvagetherapie • radicale prostatectomie Early outcomes after [ 68 Ga]PSMA-PET/CT guided salvage therapy in men with biochemical recurrence after radical prostatectomy Abstract This study was performed to assess the value of [ 68 Ga]PSMA PET/CT informed salvage therapy in men (n = 142) after radical prostatectomy with a rising prostate specific antigen PSA (0.05-0.5 ng/ml). [ 68 Ga]PSMA PET/CT scan was positive for tumor activity in 84 men (36: prostate fossa, 31 pelvic lymph nodes ± prostate fossa; 17 distant metastases. 88 men underwent salvage therapy, with a median follow-up of 12.5 months. PSA response (PSA Ä 0.01 or a >75% reduction in de latest PSA measured after salvage therapy) was recorded in 69.3% of men and found in 83% of men with a negative PET/CT, 81% of men with a positive PET/CT in the prostate fossa, and 48.5% of the men that were suspected of pelvic lymph nodes metastases on PET/CT. In conclusion, [ 68 Ga]PSMA PET/CT imaging stratifies men who responds better to salvage therapy.
World journal of urology, Jan 28, 2018
The design, conduct and completion of randomized trials for curative prostate cancer (PCa) treatm... more The design, conduct and completion of randomized trials for curative prostate cancer (PCa) treatments are challenging. To evaluate the effect of robot-assisted radical prostatectomy (RARP) versus focal irreversible electroporation (IRE) on patient-reported quality of life (QoL) and early oncological control using propensity-scored matching. Patients with T1c-cT2b significant PCa (high-volume ISUP 1 or any 2/3) who received unifocal IRE were pair-matched to patients who received nerve-sparing RARP. Patient-reported outcomes were prospectively assessed using the Expanded Prostate Cancer Index Composite (EPIC), AUA symptom score and Short Form of Health Survey (SF-12) physical and mental components. Oncological failure was defined as biochemical recurrence (RARP) or positive follow-up biopsies (IRE). Generalized mixed-effect models were used to compare IRE and RARP. 50 IRE patients were matched to 50 RARP patients by propensity score. IRE was significantly superior to RARP in preservin...
BJU international, Nov 21, 2017
To evaluate the feasibility, safety, early quality of life (QoL) and oncological outcomes of salv... more To evaluate the feasibility, safety, early quality of life (QoL) and oncological outcomes of salvage focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa). Patients with localized, radio-recurrent PCa without evidence of metastatic or nodal disease were offered focal IRE following the consensus guidelines. Patients with a minimum follow-up of 6 months were eligible for analysis. Adverse events were monitored using the NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Patient-reported QoL data was collected at baseline, 6 weeks, 3, 6 and 12 months using the Expanded Prostate Cancer Index Composite (EPIC), AUA symptom score and SF-12 Physical and Mental Component Summary (SF12-physical/SF12-mental) questionnaires. Oncological control was evaluated with serial prostate-specific antigen (PSA), 6-months multiparametric MRI (mpMRI) and 12-months prostate biopsy. Wilcoxon's Signed Rank Test was used to assess QoL differences over time ...
BJU international, May 10, 2017
To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary foc... more To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary focal IRE for the treatment of localized prostate cancer. To identify potential risk factors for oncological failure. Patients that met both the consensus guidelines on patient criteria and selection methods for primary focal therapy were eligible for analysis. Focal IRE was performed for organ-confined clinically significant PCa, being high-volume Gleason sum score 6 (ISUP grade 1) or any Gleason sum score 7 (ISUP grade 2-3). Oncologic, adverse event and QoL outcome data with a minimum of 6 months follow-up were analysed. Patient characteristics and peri-operative treatment parameters were compared for patients with and without oncological failure on follow-up biopsy. Wilcoxon's Signed Rank Test, Wilcoxon's Rank Sum Test and Chi-square test were used to assess statistically significant differences in paired continuous, unpaired continuous and categorical variables respectively. A t...
BJU international, Dec 16, 2017
To develop and externally validate a predictive model for detection of significant prostate cance... more To develop and externally validate a predictive model for detection of significant prostate cancer (PC). Development of the model was based on prospective cohort including 393 men who underwent mpMRI prior to biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent a mpMRI followed by biopsy for abnormal PSA/DRE. A model was developed with age, PSA, DRE, prostate volume, previous biopsy and PIRADS score as predictors for significant PC (Gleason 7 with >5% grade 4, ≥ 20% cores positive or ≥ 7mm of PC in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. 393 men had complete data. A total of 149 patients (37.9%) had significant PC. While the variable model had good accuracy in predicting significant PC (AUC of 0.80), the advanced model (incorporating mpMRI) had significant higher AUC of...
Aging, 2016
Prostate cancer management is complicated by extreme disease heterogeneity, which is further limi... more Prostate cancer management is complicated by extreme disease heterogeneity, which is further limited by availability of prognostic biomarkers. Recognition of prostate cancer as a genetic disease has prompted a focus on the nuclear genome for biomarker discovery, with little attention given to the mitochondrial genome. While it is evident that mitochondrial DNA (mtDNA) mutations are acquired during prostate tumorigenesis, no study has evaluated the prognostic value of mtDNA variation. Here we used next-generation sequencing to interrogate the mitochondrial genomes from prostate tissue biopsies and matched blood of 115 men having undergone a radical prostatectomy for which there was a mean of 107 months clinical follow-up. We identified 74 unique prostate cancer specific somatic mtDNA variants in 50 patients, providing significant expansion to the growing catalog of prostate cancer mtDNA mutations. While no single variant or variant cluster showed recurrence across multiple patients, we observe a significant positive correlation between the total burden of acquired mtDNA variation and elevated Gleason Score at diagnosis and biochemical relapse. We add to accumulating evidence that total acquired genomic burden, rather than specific mtDNA mutations, has diagnostic value. This is the first study to demonstrate the prognostic potential of mtDNA mutational burden in prostate cancer.
The Journal of Urology, 2016
Prostate cancer, 2016
Objective. To compare the performance of multiparametric resonance imaging/ultrasound fusion targ... more Objective. To compare the performance of multiparametric resonance imaging/ultrasound fusion targeted biopsy (MRI/US-TBx) to a combined biopsy strategy (MRI/US-TBx plus 24-core transperineal template saturation mapping biopsy (TTMB)). Methods. Between May 2012 and October 2015, all patients undergoing MRI/US-TBx at our institution were included for analysis. Patients underwent MRI/US-TBx of suspicious lesions detected on multiparametric MRI +/- simultaneous TTMB. Subgroup analysis was performed on patients undergoing simultaneous MRI/US-TBx + TTMB. Primary outcome was PCa detection. Significant PCa was defined as ≥Gleason score (GS) 3 + 4 = 7 PCa. McNemar's test was used to compare detection rates between MRI/US-TBx and the combined biopsy strategy. Results. 148 patients underwent MRI/US-TBx and 80 patients underwent MRI/US-TBx + TTMB. In the MRI/US-TBx versus combined biopsy strategy subgroup analysis (n = 80), there were 55 PCa and 38 significant PCa. The detection rate for th...
The Journal of Urology, 2016
BJU international, Jan 21, 2016
Conventional imaging techniques are inadequate for lymph node staging in prostate cancer (PC). Th... more Conventional imaging techniques are inadequate for lymph node staging in prostate cancer (PC). This study aims to assess the accuracy of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in intermediate and high-risk PC. From April to October 2015, 30 patients with intermediate (n=3) or high-risk (n=27) PC were prospectively enrolled. Patients underwent preoperative 68Ga-PSMA PET/CT. Both visual and semi quantitative analysis was undertaken. Subsequently, all patients underwent a radical prostatectomy with an extended pelvic lymph node dissection (eLND). Sensitivity, specificity, positive and negative predictive value (PPV and NPV) for LN status of 68Ga-PSMA were calculated using histopathology as reference. Eleven patients (37%) had lymph node metastases (LNMs), 26 LNMs were identified in the 11 patients. On a patient analysis, 68Ga-PSMA PET/CT has a sensitivity of 64% for the detection of LNMs, specificity was 95%, PPV was 88%, and NPV...
The Journal of Urology, 2016
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 25, 2015
In prostate cancer (PCa) and biochemical failure following therapy, current imaging techniques ha... more In prostate cancer (PCa) and biochemical failure following therapy, current imaging techniques have a low detection rate at PSA levels at which targeted salvage therapy is effective. (11)C-Choline or (18)F-Fluoromethylcholine (FMC), though widely used, have poor sensitivity at low PSA levels. (68)Ga-PSMA-HBED (PSMA) has shown promising results in retrospective trials. Our aim is to prospectively compare detection rates of PSMA versus FMC PET/CT in men initially managed with either radical prostatectomy (RP), radiation treatment (RT) or both, being considered for targeted therapy. A sample of men with rising PSA following treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. PSMA, FMC PET/CT and diagnostic CT were undertaken in all patients sequentially between January and April 2015, and assessed by blinded experienced readers. Scan results and management impact changes, together with histological follow-up when feasibl...
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Papers by phillip stricker