Zie ook de literatuurlijsten niet-toxische middelen en behandelingen specifiek bij de verschillende vormen van kanker en bij chemo, bestraling en operaties van arts-bioloog drs. Engelbert Valstar

En weet dat u als donateur ook korting kunt krijgen op o.a. prostasol bij MEDPRO

13 november 2023: zie ook dit artikel: https://kanker-actueel.nl/theranostiek-succesvol-bij-prostaatkanker-en-schildklierkanker-lijkt-ook-interessante-behandeling-voor-borstkanker-te-kunnen-zijn-aldus-prof-dr-dalm-uit-erasmus-mc.html

28 oktober: lees ook dit artikel: https://kanker-actueel.nl/immuuntherapie-met-p-psma-101-car-t-celtherapie-gericht-op-pmsa-geeft-veelbelovende-resultaten-met-zelfs-een-complete-remissie-bij-10-zwaar-voorbehandelde-patienten-met-vergevorderde-uitgezaaide-hormoonresistente-prostaatkanker.html

28 oktober 2022: Lees ook deze nieuwe overzichtstudie hoe om te gaan met op PMSA gerichte bestraling en andere behandelingen (onderaan abstract):

Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond

PRAKTISCHE TOEPASSINGEN

Er zijn gestandaardiseerde criteria in PSMA PET/CT voor de selectie van patiënten voor 177Lu-PSMA-radionuclidetherapie (RNT) vastgesteld, maar verdere verfijning om de therapeutische respons te verbeteren is gerechtvaardigd.
Prognostische factoren voor de uitkomst na 177Lu-PSMA RNT werden geïdentificeerd en opgenomen in nomogrammen om te helpen tijdens het selectieproces van de patiënt.
Bijdragende factoren van resistentie tegen op PSMA gebaseerde RNT zijn onder meer heterogeniteit van tumor-PSMA-expressie, het niet afleveren van een dodelijke dosis straling op metastatische locaties, de micro-omgeving van de tumor en biologische radioresistentie van de tumor.
Het combineren van op PSMA gebaseerde RNT met potentieel synergetische middelen (bijv. immuuncheckpointremmers, PARP-remmers, antiandrogenen, CDK-4/6-remmer) of RNT met α-emitters kan de therapeutische respons verbeteren.
Andere biologische doelwitten dan PSMA toonden potentieel voor theranostische toepassingen bij prostaatkanker en worden momenteel onderzocht.

1 mei 2020: Aanvullend op onderstaande informatie zie ook dit studierapport: Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

PSMA PET / CT werd geassocieerd met een grotere nauwkeurigheid dan conventionele beeldvorming (92% versus 65%). De verbeterde nauwkeurigheid van PSMA PET / CT resulteerde in behandelingswijzigingen en een lagere blootstelling aan straling.

13 december 2019: Bron: Journal of Urology

De komst van de zogeheten Ga-PSMA-11 PET-scanning in de opsporing van uitzaaiingen van prostaatkanker bij mannen met oplopende PSA waarden heeft de praktijk van de aanpak van prostaatkanker wel veranderd. In Australië hebben ze nu 4 jaar ervaring hiermee en hebben een analyse gemaakt van totaal 191 patienten die na oplopende PSA waarden een PSMA scan / behandeling hebben gehad. De studie bevestigt in principe de nutteloosheid van het gebruik van een traditionele CT-scan en/of botscan bij uitgezaaide prostaatkanker nadat de PSA na een operatie - prostatectomie is gestegen. Zelfs bij zeer lage niveaus van PSA na de operatie, blijkt via PSMA PET-scanning alle uitzaaiingen in lymfklier, botten en viscerale tumoren te ontdekken.

Een PSMA Pet / CT scan met lutetium-177 wat ook vaak wordt gebruikt is tegelijk een behandeling omdat er gericht "bestraald" wordt op een zogeheten PSMA ligand, een eiwit dat gevoelig blijkt voor de radionuclide Gallium 68, een stofje dat gebruikt wordt in de PSMA pet / CT scan en tegelijk met de diagnose (de tumorcellen lichten op) de tumorcellen ook vernietigt.

In het Anthonius ziekenhuis in Nieuwegein werken ze ook al enkele jaren met de PSMA petscan:

"Met de PSMA PET-scan kunnen we eventuele uitzaaiingen veel eerder vaststellen. Je ziet ze al terwijl het PSA (een bepaalde eiwitwaarde in het bloed - red.) nog heel laag is", aldus Lavalaye. "Ook zien we precies waar ze zitten. Belangrijke kennis, waardoor je in veel gevallen samen met de patiënt en het behandelteam direct voor de best mogelijke behandeling kunt kiezen."
Het St. Antonius was vorig jaar het eerste Nederlandse ziekenhuis dat over de nieuwe scantechniek beschikte. "De technieken die we eerder gebruikten voor dit doel, zagen vaak afwijkingen over het hoofd", licht Lavalaye toe. "De PSMA PET-scan toont ze wél aan. Dat kan voorkomen dat we iemand onnodig gaan opereren, terwijl hij baat heeft bij een andere behandeling, zoals radiotherapie. Daarmee bespaar je de patiënt de stress van een operatie en voorkom je dat kostbare tijd verloren gaat."

Resultaten uit de Australische studie bevestigen bovenstaande:

De PSMA petscan ontdekte gelokaliseerde prostaatkanker bij 130 van 191 patiënten (68%) met PSA oplopende waarden met een mediane PSA van 1,1 ng / ml. De detectiesnelheid nam significant toe met de snelheid van oplopende PSA waarden. (p <0,001).

Met betrekking tot de PSMA petscan resultaten/ via een gecomputeriseerde tomografie had slechts 61 van 173 patiënten (35%) een ziekte die beperkt was tot het bekken, terwijl 57 van 173 patienten (33%) tumoren op afstand hadden.

De meest aangetaste lymfkliergebieden waren de obturator bij 42% en het presacrale / mesorectale gebied bij 40% van de patienten. Bij 15 van de 33 patiënten (45%) met een PSMA petscan uitslag voor en na de operatie werd ten minste 1 tumor gedetecteerd bij aanvang via de PSMA scan, 8 patienten (24%) hadden nieuwe tumoren en 10 (30%) hadden geen nieuwe uitzaaiingen volgens de PSMA petscan.

De positief voorspellende waarde van een PSMA petscan was 91%. Start van systemische therapie was significant geassocieerd / gerelateerd met uitzaaiingen op afstand gevonden door de PSMA petscan.

Het volledige studierapport: 68Ga-PSMA-11 Positron Emission Tomography Detects Residual Prostate Cancer after Prostatectomy in a Multicenter Retrospective Study is tegen betaling in te zien.

Hier het abstract van de studie:

View All Author Information

https://doi.org/10.1097/JU.0000000000000417

Abstract

Purpose:

Prostate specific antigen persistence after radical prostatectomy is associated with adverse outcomes in patients with prostate cancer. We sought to define regions at risk for residual disease as well as the accuracy of prostate specific membrane antigen ligand positron emission tomography in patients with prostate specific antigen persistence.

Materials and Methods:

At 6 participating centers a total of 191 patients who underwent 68Ga-prostate specific membrane antigen-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging for persistently elevated postoperative prostate specific antigen (0.1 ng/ml or greater) were retrospectively included in study. The detection rate and the positive predictive value were determined. In 33 patients with additional prostate specific membrane antigen ligand positron emission tomography before prostatectomy we also determined the rate of positron emission tomography based persistence and recurrence.

Results:

Prostate specific membrane antigen ligand positron emission tomography localized prostate cancer in 130 of 191 patients (68%) with prostate specific antigen persistence at a median prostate specific antigen of 1.1 ng/ml. The detection rate significantly increased with prostate specific antigen (p <0.001). Regarding prostate specific membrane antigen positron emission tomography/computerized tomography only 61 of 173 patients (35%) had disease confined to the pelvis while 57 of 173 (33%) had distant lesions. The most frequently affected nodal regions were the obturator in 42% and the presacral/mesorectal region in 40%. In 15 of the 33 patients (45%) with prostate specific membrane antigen ligand positron emission tomography before and after surgery at least 1 lesion was detected at baseline (positron emission tomography persistence), 8 (24%) had new lesions (positron emission tomography recurrence) and 10 (30%) had negative positron emission tomography findings. The positive predictive value of prostate specific membrane antigen ligand positron emission tomography was 91%. Systemic therapy initiation was significantly associated with distant lesions on prostate specific membrane antigen ligand positron emission tomography.

Conclusions:

Prostate specific membrane antigen ligand positron emission tomography localized prostate cancer in more than two-thirds of patients with high risk features and prostate specific antigen persistence after prostatectomy. Obturator and presacral/mesorectal nodes are at high risk for persistent metastasis.

Deze volgende studie is recent gepubliceerd:

Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond

Andrei Gafita, MD1; Charles Marcus, MD2; Louise Kostos, MBBS3; David M. Schuster, MD2; Jeremie Calais, MD1; and Michael S. Hofman, MBBS4,5Show More

ABSTRACT

PSMA is a transmembrane protein that is markedly overexpressed in prostate cancer, making it an excellent target for imaging and treating patients with prostate cancer. Several small molecule inhibitors and antibodies of PSMA have been radiolabeled for use as therapeutic agents and are currently under clinical investigation. PSMA-based radionuclide therapy is a promising therapeutic option for men with metastatic prostate cancer. The phase II TheraP study demonstrated superior efficacy, lower side effects, and improved patient-reported outcomes compared with cabazitaxel. The phase III VISION study demonstrated that radionuclide therapy with β-emitter 177Lu-PSMA-617 can prolong survival and improve quality of life when offered in addition to standard-of-care therapy in men with PSMA-positive metastatic castration-resistant prostate cancer whose disease had progressed with conventional treatments. Nevertheless, up to 30% of patients have inherent resistance to PSMA-based radionuclide therapy, and acquired resistance is inevitable. Hence, strategies to increase the efficacy of PSMA-based radionuclide therapy have been under clinical investigation. These include better patient selection; increased radiation damage delivery via dosimetry-based administered dose or use of α-emitters instead of β-emitters; or using combinatorial approaches to overcome radioresistance mechanisms (innate or acquired), such as with novel hormonal agents, PARP inhibitors, or immunotherapy.

PRACTICAL APPLICATIONS

Standardized criteria in PSMA PET/CT for patient selection for 177Lu-PSMA radionuclide therapy (RNT) have been established, but further refinement to enhance therapeutic responses is warranted.
Prognostic factors for outcome after 177Lu-PSMA RNT were identified and included in nomograms to assist during the patient selection process.
Contributing factors of resistance to PSMA-based RNT include heterogeneity of tumor PSMA expression, failure to deliver a lethal dose of radiation to metastatic sites, tumor microenvironment, and tumor biological radioresistance.
Combining PSMA-based RNT with potentially synergistic agents (e.g., immune checkpoint inhibitors, PARP inhibitors, antiandrogens, CDK-4/6 inhibitor) or RNT with α-emitters may improve therapeutic responses.
Biological targets other than PSMA showed potential for theranostic applications in prostate cancer and are currently being investigated.

PSMA is a type 2 membrane glycoprotein that is expressed selectively by prostate cells, with expression level increasing dramatically in malignant prostatic tissue.1 Because of its properties, PSMA has emerged as an attractive target for theranostics in prostate cancer.2 In the past decade, numerous imaging and therapeutic radiopharmaceuticals targeting PSMA have been developed and investigated in clinical trials.3 –8 PSMA-based radionuclide therapy (RNT) is a promising therapeutic option for men with metastatic prostate cancer.5 PSMA radioligands are internalized after binding to the target, enabling delivery of radiation directly into the malignant cells.

The β-emitting radioisotope 177Lu conjugated with small molecule PSMA-617 (177Lu-PSMA-617) is the PSMA-based RNT currently furthest along in clinical development. The VISION study, an international, open-label, randomized phase III trial, demonstrated that 177Lu-PSMA-617 can prolong survival and improve quality of life when offered in addition to standard care in men with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) whose disease had progressed with taxanes and novel antiandrogens.5 In this trial, 831 patients were randomly assigned in a 2:1 ratio to 177Lu-PSMA-617 (7.4 GBq every 6 weeks for six cycles; 551 patients) plus best standard of care or standard of care alone (280 patients). The trial met both primary endpoints of overall survival (OS) and radiographic progression-free survival (PFS). The median OS was 15.3 months in the 177Lu-PSMA-617 arm versus 11.3 months in the standard of care–alone arm, resulting in a 38% reduction in the risk of death. The median radiographic PFS was 8.7 versus 3.4 months, respectively. Another randomized trial (TheraP) showed that 177Lu PSMA-617 led to higher prostate-specific antigen (PSA) response rates (66% vs. 37%), superior PFS (HR, 0.63), and fewer grade 3 or 4 adverse effects compared with cabazitaxel in men with mCRPC whose disease progressed after docetaxel.9

The U.S. Food and Drug Administration recently approved 177Lu-PSMA-617 for men with PSMA-positive mCRPC previously treated with androgen receptor–targeted agents and taxane-based chemotherapy.10 Nevertheless, a subset of patients has inherent resistance to PSMA-based RNT (approximately 30% in VISION5 and 17% in TheraP9), and acquired resistance is inevitable. Hence, strategies to increase the efficacy of PSMA-based RNT have been under clinical investigation. These include better patient selection; increased radiation damage delivery via dosimetry-based administered dose or use of α-emitters instead of β-emitters; or use of combinatorial approaches to overcome radioresistance mechanisms (innate or acquired), such as with novel hormonal agents, PARP inhibitors, or immunotherapy. In this article, we provide an overview of the currently available and forthcoming PSMA-based RNT and discuss approaches aimed at improving the efficacy and safety of PSMA-based RNT.

References

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST AND DATA AVAILABILITY STATEMENT

Disclosures provided by the authors and data availability statement (if applicable) are available with this article at DOI https://doi.org/10.1200/EDBK_350946.

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc.

DAVID SCHUSTER

Employment: Ascend Imaging (I)

Consulting or Advisory Role: AIM Specialty Health; Syncona; Progenics; Global Medical Solutions

Research Funding: Blue Earth Diagnostics (Inst); Nihon Medi-Physics (Inst); Advanced Accelerator Applications (Inst); Telix Pharmaceuticals (Inst); FUJIFILM (Inst); Amgen (Inst)

Patents, Royalties, Other Intellectual Property: Inventor(s): Miller, Matthew (Oxford, GB), Gauden, David (Oxford, GB), Schuster, David (Atlanta, GA), Fanti, Stefano (Bologna, IT), Nanni, Cristina (Bologna, IT), Zanoni, Lucia (Bologna, IT), Willoch, Frode (Oslo, NO), Bogsrud, Trond Velde (Oslo, NO), Bach-Gansmo, Tore (Oslo, NO), Musto, Title: Imaging of metastatic or recurrent cancer Publication Number: US 20200316228 A1 Assignee: Blue Earth Diagnostics Limited (Oxford, GB) Filing Date: June 22, 2020 Granted: April 6, 2021

JEREMIE CALAIS

Honoraria: Radiomedix; Progenics; Advanced Accelerator Applications; EXINI Diagnostics

Consulting or Advisory Role: Blue Earth Diagnostics; Janssen; Progenics; Curium Pharma; GE Healthcare; Telix Pharmaceuticals; POINT Biopharma; Lantheus Medical Imaging

Speakers' Bureau: Telix Pharmaceuticals; IBA RadioPharma Solutions

Research Funding: Progenics

MICHAEL HOFMAN

Consulting or Advisory Role: Endocyte; Janssen; POINT Biopharma

Speakers' Bureau: Janssen; Mundipharma; Astellas Pharma; AstraZeneca

Research Funding: Endocyte (Inst); Advanced Accelerator Applications/Novartis (Inst)

Travel, Accommodations, Expenses: Ipsen; Genzyme; Janssen

No other potential conflicts of interest were reported.

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PSMA, petscan, 68Ga–prostate-specific membrane antigen (PSMA) ligand PET imaging, uitzaaiingen op afstand, radiotherapie, bestraling

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e.valstar :
14/12/2019
Prachtig dat het allemaal eerder en duidelijker te zien is, maar waar is de randomised controlled clinical trial die aantoont dat daarop gericht eerder behandelen door bestralen de prognose verbetert? wie kan mij dat onderzoek tonen? Ik ken alleen maar aanwijzingen dat dit eerder in kaart brengen de prognose niet verbetert.

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Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond

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1 Reactie op "PSMA gerichte PET scan bij mannen met verhoogde PSA is effectieve manier in ontdekken van plaats van tumoren. Bij uitzaaiingen op afstand heeft bestralen van bekkengebied geen zin."

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