Prostate cancer is dependent on the action of steroid hormones on the receptors. Endocrine therapy inhibits hormone production or blocks the receptors, thus providing clinical benefit to many, but ...not all, oncological patients. It is difficult to predict which patient will benefit from endocrine therapy and which will not. Positron Emission Tomography (PET) imaging of androgen receptors (AR) may provide functional information on the likelihood of endocrine therapy response in individual patients. In this article, we review the utility of
FFDHT-PET imaging in prostate, breast, and other hormone-dependent cancers expressing AR. The methodologies, development, and new possibilities are discussed as well.
Aims
There is a controversy as to the relative efficacy of
177
Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic ...castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether
177
Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743).
Methods
The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in
ClinicalTrials.gov
indicated ongoing studies. The meta-analysis used the random-effects model.
Results
Twelve studies including 669 patients reported
177
Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with
177
Lu-PSMA RLT. The treatment with
177
Lu-PSMA-617 and
177
Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients.
177
Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%,
p
= 0.0002,
t
test).
177
Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients,
p
= 0.004, χ
2
test). Median survival was longer after
177
Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months,
p
= 0.32,
t
test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for
177
Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients,
p
< 0.001, χ
2
test).
Conclusions
As for patients with mCRPC, treatment with
177
Lu-PSMA-617 RTL and
177
Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.
The results of 1174 therapy cycles (a median of two cycles IQR 2–4 per patient) are very convincing, because a substantial antitumour effect (prostate-specific antigen PSA decline of ≥50%) occurred ...in 278 (57%) patients, and a median overall survival of 15·5 months (95% CI 13·4–18·3) and progression-free survival of 7·9 months (6·8–8·9) were observed in this late stage of prostate cancer. The previous retrospective multicentre analyses regarding Lutetium-177 (177Lu)-PSMA RLT in mCRPC by the WARMTH community3,4 found multiple factors associated with overall survival and progression-free survival and were also able to predict overall survival and progression-free survival before actual registration trials (TheraP5 and VISION6) reported data. Prostate cancer development both in the cell membranes and cytoplasm is associated with increased PSMA activity, which is not seen in benign prostate hyperplasia.8 For PSMA-targeting radiopharmaceuticals, the administered activities have been found by dose escalation to minimise side-effects and to maximise tumour destruction.
Introduction
The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving
177
LuLu-PSMA-617 therapy has ...been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with
177
Lu-PSMA-617.
Materials and methods
The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to
177
LuLu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated.
Results
The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.
Conclusion
In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving
177
LuLu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS.
Introduction
Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the ...presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.
Methods
The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with
177
LuLu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6–20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Results
A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6–20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (
p
< 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6–20 lesions (OS: 16 vs. 12 months;
p
= 0.038) as well as diffuse involvement (OS: 11 vs. 7 months;
p
= 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases:
p
< 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia.
Conclusion
The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.
The purpose of this study was to evaluate the outcome after Radium-223-dichloride ((223)RaCl₂) treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body ...(18)F-Fluoride PET/CT. Sodium (18)F-fluoride (18)F-NaF PET/CT was performed prior the treatment of (223)RaCl₂, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in (18)F-NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with (18)F-NaF response, only 1 patient demonstrated progressive disease, i.e., >25% increase in S-PSA values during (223)RaCl₂. Our results (although preliminary) suggest that (18)F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases.
This article is a short review of PET tracers, which have been used in clinical routine in single institutions. Preliminary anecdotal research supports the use of PET techniques in therapy planning ...of prostate cancer. The existing literature is discussed. For external beam radiation therapy, the biological target volume definition can only be based on PET imaging. There are not yet any prospective and randomized trials available; therefore, single-institution experiences cannot yet be recommended as clinical routine.
Pancreatic ductal adenocarcinoma (PDAC), which ranks forth on the cancer-related death statistics still is both a diagnostic and a therapeutic challenge. Adenocarcinoma of the exocrine human pancreas ...originates in most instances from malignant transformation of ductal epithelial cells, alternatively by Acinar-Ductal Metaplasia (ADM). RA-96 antibody targets to a mucin M1, according to the more recent nomenclature MUC5AC, an extracellular matrix component excreted by PDAC cells. In this study, we tested the usability of multimodal nanoparticle carrying covalently coupled RA-96 Fab fragments for pancreatic tumor imaging.
In order to make and evaluate a novel, better targeting, theranostic nanoparticle, iron nanoparticles and the optical dye indocyanin green (ICG) were encapsulated into the cationic sphingomyelin (SM) consisting liposomes. RA-96 Fab fragment was conjugated to the liposomal surface of the nanoparticle to increase tumor homing ability. ICG and iron nanoparticle-encapsulated liposomes were studied in vitro with cells and (i) their visibility in magnetic resonance imaging (MRI), (ii) optical, (iii) Magnetic particle spectroscopy (MPS) and (iv) photoacoustic settings was tested in vitro and also in in vivo models. The targeting ability and MRI and photoacoustic visibility of the RA-96-nanoparticles were first tested in vitro cell models where cell binding and internalization were studied. In in vivo experiments liposomal nanoparticles were injected into the tail vain using an orthotopic pancreatic tumor xenograft model and subcutaneous pancreatic cancer cell xenografts bearing mice to determine in vivo targeting abilities of RA-96-conjugated liposomes Results: Multimodal liposomes could be detected by MRI, MPS and by photoacoustic imaging in addition to optical imaging showing a wide range of imaging utility. The fluorescent imaging of ICG in pancreatic tumor cells Panc89 and Capan-2 revealed an increased association of ICG-encapsulated liposomes carrying RA-96 Fab fragments in vitro compared to the control liposomes without covalently linked RA-96. Fluorescent molecular tomography (FMT) studies showed increased accumulation of the RA96-targeted nanoparticles in the tumor area compared to non-targeted controls in vivo. Similar accumulation in the tumor sites could be seen with liposomal ferric particles in MRI. Fluorescent tumor signal was confirmed by using an intraoperative fluorescent imaging system, which showed fluorescent labeling of pancreatic tumors.
These results suggest that RA-96-targeted liposomes encapsulating ICG and iron nanoparticles can be used to image pancreatic tumors with a variety of optical and magnetic imaging techniques. Additionally, they might be a suitable drug delivery tool to improve treatment of PDAC patients.
Serum prostate-specific antigen (PSA) needs to be monitored with ultrasensitive PSA assays (uPSAs) for oncologists to be able to start salvage radiotherapy (SRT) while PSA is <0.5 µg/L for patients ...with prostate cancer (PCa) relapsing after a radical prostatectomy (RP). Our systematic review (SR) aimed to summarize uPSAs for patients with localized PCa. The SR was registered as InPLASY2023110084. We searched for studies on Google Scholar, PUBMED and reference lists of reviews and studies. We only included studies on uPSAs published in English and excluded studies of women, animals, sarcoidosis and reviews. Of the 115 included studies, 39 reported PSA assay methods and 76 reported clinical findings. Of 67,479 patients, 14,965 developed PSA recurrence (PSAR) and 2663 died. Extremely low PSA nadir and early developments of PSA separated PSAR-prone from non-PSAR-prone patients (cumulative
value 3.7 × 10
). RP patients with the lowest post-surgery PSA nadir and patients who had the lowest PSA at SRT had the fewest deaths. In conclusion, PSA for patients with localized PCa in the pre-PSAR phase of PCa is strongly associated with later PSAR and survival. A rising but still exceedingly low PSA at SRT predicts a good 5-year overall survival.
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