Урология №2 / 2025
Эффективность и побочные эффекты 177Лютеций-ПСМА-617 у пациентов с метастатическим кастрационно-рефрактерным раком предстательной железы: систематический обзор и метаанализ
1) Кафедра урологии, факультет медицинских наук и здоровья Университета Путра, Малайзия;
2) Отделение урологии, Больница Султана Абдул Азиза Шаха, Университет Путра, Малайзия
Введение. Прогрессирование метастатического рака предстательной железы после развития резистентности к кастрации является одной из основных проблем в лечении данного заболевания. В ряде исследований изучали радионуклидную терапию 177Lu-PSMA-617 у больных метастатическим кастрационно-рефрактерным раком предстательной железы.
Цель. Провести систематическую оценку эффективности и профиля безопасности 177Lu-PSMA- 617.
Материалы и методы. Проведен систематический обзор и метаанализ в соответствии с принципами PRISMA. Из 261 публикации критериям включения соответствовало три рандомизированных исследования. Первичным оцениваемым критерием был онкологический результат и побочные эффекты. Для проведения систематического обзора и метаанализа использовали программу RevMan 5.4.
Результаты. Всего в анализ включены данные 1071 пациента, из них 670 (62,6%) проводилась радионуклидная терапия 177Lu-PSMA- 617. В лечебной группе выживаемость без прогрессирования была статистически значимо выше с отношением риска 0,72 (p=0,00001). Снижение уровня ПСА более чем на 50% наблюдалось у 75 (63%) и 45/121 пациентов (37,2%) (p=0,0001). Нежелательные явления встречались у 572/627 (91,2%) и 204/290 (70,3%) больных соответственно (p=0,00001). Усталость описана у 306/647 (47,3%) и 88/310 (28,4%) пациентов (p=0,00001), а запоры – у 110/549 (20%) и 24/225 (10,7%) (p=0,003) соответственно. Тромбоцитопения и лейкопения несколько чаще развивались в лечебной группе, у 114/647 (17,6%) и 19/310 (6,1%) (p=0,08) и 81/647 (12,5%) и 13/310 (4,2%) (p=0,10) соответственно.
Выводы. Радионуклидная терапия 177Lu-ПСМА-617 позволяет снизить уровень ПСА и улучшить выживаемость без прогрессирования. Терапия имеет приемлемый профиль побочных эффектов, которые включают в основном усталость, запоры, тромбоцитопению и лейкопению.
Introduction. Prostate cancer is the second most common cancer affecting men and is considered the fifth leading cancer-related cause of death [1]. For many years, Androgen deprivation therapy has been the gold standard treatment for advanced prostate cancer [2]. A lot of research efforts have been directed to explore and understand the molecular basis of metastatic prostate cancer, that resulted in expanding the options for treatment of metastatic prostate cancer. Yet the resistance of this disease to castration remains the main challenge for the researchers in this area [3].
The aim of the given treatment for metastatic prostate cancer is to control the progression of the disease or to prolong the survival, rather than to cure the disease. Chemotherapeutic agents such as docetaxel and cabazitaxel have shown prolonged overall survival in patients with metastatic castration-resistant prostate cancer [4]. Similar results were recorded for the new anti-androgen receptor blockers such as abiraterone and enzalutamide [5]. And these novel agents have demonstrated prolonged progression-free survival in non-metastatic castration resistant prostate cancer as well [6].
Targeted radionuclide treatment (also known as molecular radiotherapy) employs a radioactive substance known as a radiopharmaceutical that specifically targets cancer cells. A radioactive atom (also known as a radionuclide) is often paired with a cell-targeting chemical that finds and destroys cancer cells in radiopharmaceuticals [7]. PSMA (prostate-specific membrane antigen) is a transmembrane glutamate carboxypeptidase, which is abundant in prostate cancer cells [8]. It is possible to deliver high activities of Lutetium-177-PSMA-617 to PSMA expressing prostate cancer cells with only minimal damage to the surrounding normal tissues. This is because 177Lu is a medium-energy beta emitter, with a beta-particle range of 2 mm and a physical half-life of 6.7 days [9]. Recent studies showed that 177Lu-PSMA-617 therapy might help to control the progression of prostate cancer in castration-resistant patients, however, the available data on the efficacy and tolerability of this modality are limited [10, 11]. The aim of this systematic review and meta-analysis is to assess the efficacy and side effects of 177Lu-PSMA-617 in patients with castration resistant prostate cancer based on the available randomized controlled trials.
Materials and methods
Search Strategy
Online systemic search through online electronic databases (PubMed, EMBASE, Wiley Online Library, and Cochrane databases) was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria [12]. The following keywords were used during the search: metastatic prostate cancer, castration resistant, PSMA, prostate specific membrane antigen, Lutetium 177, targeted radiotherapy. The following exclusion criteria were applied: (1) review articles, (2) case reports, (3) letters to editors and editorial comments, (4) repeated publications, (5) nonrandomized trials, and (6) clinical trial protocols. All the obtained results, initially assessed by the title, with or without abstract assessment. Eligible studies underwent full-text assessment. The manual search in reference lists of relevant published studies was conducted to avoid missing any eligible studies. Eventually, we included the randomized controlled trials.
Data Extraction
Two authors have extracted the data independently and checked by the third one. Discussion among the three authors was conducted to resolve any discrepancies. Extracted data were main author and year of publication, timeframe of the study, type of the study and registration number, given treatment, ...
