Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland: A real-world evidence multicenter study

Prostate cancer is the second most commonly diagnosed cancer type and the sixth leading cause of cancer-related death among men worldwide. The prognosis for localized prostate cancer is good, with 5-year survival rates over 90%. However, some cases will afterwards recur and about 20% of patients present with distant metastases at the time of primary diagnosis. Bone and lymph node metastasis are typical in prostate cancer. The first-line treatment option for metastatic prostate cancer is androgen deprivation therapy (ADT) that can be combined with docetaxel chemotherapeutic agent or drugs interfering with androgen signaling in early castration naïve state. Eventually, most of these patients develop a state entitled metastatic castration-resistant prostate cancer (mCRPC) where currently no curative treatments are available. Radium-233 dichloride is an alpha emitter with a half-life of 11.4 days, specifically targeting bone metastases in prostate cancer. Previously reported phase III randomized trial showed safety for radium-223 and survival benefit compared to best supportive care in CRPC with bone metastases. The aim of this retrospective study was to study the realworld results of radium-223 treatment in mCRPC. Our retrospective multicenter study included all patients with mCRPC treated with radium-223 outside of clinical trials in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had been treated with radium-223 in Finland between 2014-2019. Our study confirmed that radium-223 was well tolerated in routine clinical practice. Most patients achieved pain relief during radium-223 treatment. The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Pain relief, alkaline phosphatase normalization, lower baseline PSA, and PSA decrease during radium-223 treatment were prognostic for better survival. Our results are in line with earlier realworld studies and support using radium-223 for mCRPC patients with symptomatic bone metastases.Eturauhassyöpä on miesten yleisin syöpä Suomessa ja aiheuttaa miehillä toiseksi eniten syöpäkuolemia keuhkosyövän jälkeen. Paikallisen eturauhassyövän ennuste on hyvä, mutta levinneeseen eturauhassyöpään ei ole parantavaa hoitoa tarjolla. Levinneen kastraatioresistentin eturauhassyövän perinteisten solusalpaajahoitojen ja androgeenireseptorin viestintään vaikuttavien lääkkeiden lisäksi on kehitetty radionuklidihoitoja, joiden toiminta perustuu radionuklidien emittoimaan radioaktiiviseen säteilyyn. Radium-223 on luuhun hakeutuva alfa-säteilevä radionuklidi, jonka on osoitettu faasi 3 tutkimuksessa lisäävän kokonaiselossaoloaikaa ja parantavan elämänlaatua kastraatioresistentissä luustoon levinneessä eturauhassyövässä. Tutkimuksen tavoitteena oli selvittää radium-223 hoitojen tulokset tosielämässä. Tämä monikeskustutkimus kattoi kaikki Suomen yliopistosairaaloissa hoidetut radium-223 potilaat (n=160) hoitotutkimusten ulkopuolella, vuosina 2014-2019. Tutkimus osoitti radium-223 hoitojen olevan hyvin siedettyjä tosielämässä. Suurin osa potilaista sai kivunlievitystä radium-223 hoidoista. Mediaani kokonaiselossaoloaika oli 13,8 kuukautta (0,5-57 kk) ja mediaani tosielämän etenemisvapaa elossaoloaika 4,9 kuukautta (0,5-29,8 kk). Tuloksemme ovat verrattavissa aikaisempiin retrospektiivisiin tosielämän tutkimuksiin. Kivunlievittyminen, AFOS-arvojen normalisoituminen viitteisiin, matala lähtötilanteen PSA ja PSA:n lasku radium-223 hoitojen aikana ennustivat parempaa kokonaiselossaoloaikaa. Tuloksemme tukevat radium-223 käyttöä metastaattista kastraatioresistenttiä eturauhassyöpää sairastavilla potilailla, joilla on oireisia luustometastaaseja

More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond

Simple SummaryProstate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in prostate cancer and correlates with the aggressiveness of the disease. PSMA is a promising target for imaging and therapeutics in prostate cancer patients validated in prospective trials. However, the role of PSMA in prostate cancer progression is poorly understood. In this review, we discuss the biology and scientific rationale behind the use of PSMA and other targets in the detection and theranostics of metastatic prostate cancer.Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland : A real-world evidence multicenter study

Background Radium-233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium-223 compared to best supportive care in castration-resistant prostate cancer (CRPC) with bone metastases. However, real-world data are also needed with wider inclusion criteria. Methods We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium-223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium-223 in Finland in 2014-2019. Results The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium-223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p = 100 mu g/L) before radium-223 treatment was associated with poor OS compared to low PSA level (Peer reviewe

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland : A real-world evidence multicenter study

Background Radium-233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium-223 compared to best supportive care in castration-resistant prostate cancer (CRPC) with bone metastases. However, real-world data are also needed with wider inclusion criteria. Methods We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium-223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium-223 in Finland in 2014-2019. Results The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium-223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p = 100 mu g/L) before radium-223 treatment was associated with poor OS compared to low PSA level (Peer reviewe