مقاله انگلیسی رایگان در مورد جهات درمان جدید سرطان پروستات – الزویر 2024

Abstract

Purpose
There is scarce comparative effectiveness research on the new treatment modalities for localized prostate cancer. We aim to compare through Patient-Reported Outcome Measures (PROMs) the impact of active surveillance, robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and real-time brachytherapy, considering side effects (incontinence, irritative/obstructive urinary symptoms, sexual dysfunction and bowel symptoms) and physical and mental health.

Materials and Methods
Prospective cohort of men diagnosed with clinically localized prostate cancer (age 50-75y, T1-T2, and low risk including Gleason 3 + 4 in T1c) from 18 Spanish hospitals, followed up to 24 months. Treatment decisions were jointly made by patients and physicians (n = 572). The Expanded Prostate cancer Index Composite (EPIC-26) and Short-Form 36 (SF-36v2) were administered through telephone interviews before and three, six, 12, and 24 months after treatment. To account for correlation among repeated measures, generalized estimating equation models were constructed. All analyses were performed with propensity score weights to solve treatment selection bias.

Results
The PROMs completion rate at 24 months was 95.0 %. Active surveillance entails the fewest side effects, but with significant sexual (0.4 standard deviations [SD], p < 0.001) and physical health deterioration (0.5 SD, p < 0.001); and moderate mental health improvement (0.4 SD, p = 0.001) at 24 months. Compared with active surveillance, RARP presented greater urinary incontinence (p = 0.030), and IMRT and real-time brachytherapy worse bowel symptoms (p = 0.027 and p = 0.007) at 24 months.

Conclusions
Most side effects of the new treatment modalities seem to be limited to short-term deteriorations, except for moderate-large urinary incontinence in patients who had undergone RARP and moderate bowel deterioration in patients treated with IMRT or with real-time brachytherapy. Furthermore, patients under active surveillance, IMRT, and real-time brachytherapy showed a moderate improvement in mental health.

Introduction

Prostate cancer is the most frequently diagnosed non-cutaneous cancer among men in USA and Europe [1], and most patients are diagnosed in localized stages [2], becoming long-term survivors [3]. Randomized controlled trials of curative intention treatments for localized prostate cancer are mainly restricted to the ProtecT (Prostate Testing for Cancer and Treatment) trial [4], [5]. This study showed similar very high rates of survival at ten years of follow-up [4] for radical prostatectomy, external beam radiotherapy and active monitoring, though differing in their side effects’ patterns, evaluated with Patient-Reported Outcome Measures (PROMs) [5]. ProtecT patients were treated in the early 2000s with open retropubic radical prostatectomy, external beam 3D-conformal radiotherapy (delivered at 74 Gy in 37 fractions), and active monitoring.

New modalities of the same treatments are being widely used, such as robot-assisted radical prostatectomy (RARP), intensity-modulated radiation therapy (IMRT), or real-time brachytherapy, with the theoretical justification that they are less aggressive and could achieve maximum efficacy in oncological results with a lower rate of side effects. RARP has shown to be an easily acquired laparoscopic technique, with shorter learning curves than the open procedure [6]. IMRT has allowed treating patients with higher doses of radiation, without increasing toxicity in surrounding healthy tissues [7]. Real-time brachytherapy allows correcting radioactive seed distribution and doses at the time of their implantation, achieving better target coverage and sparing normal tissues [8].

The rapid adoption of newer modalities has introduced additional uncertainty to the decision-making process. On the one hand, despite the theoretical advantages, the randomized clinical trial comparing RARP with open radical prostatectomy did not find significant benefits in PROMs [9]. On the other hand, the randomized clinical trial comparing IMRT with 3-D conformal radiotherapy reported differences in urinary, bowel and other treatment-related symptoms, in favor of the new technique [7]. The only recent study comparing real-time with pre-planned low-dose rate brachytherapy as a monotherapy did not show any differences in toxicity, though PROMs were not included [8].

Conclusions

In conclusion, in this cohort of men with localized prostate cancer strictly treated with new treatment modalities, side effects mainly disappeared by the 24-month follow-up, except for the moderate-large urinary incontinence in patients who underwent RARP and the moderate bowel deterioration in those treated with IMRT and brachytherapy. Therefore, most side effects of new treatment modalities seem to be limited to short-term deteriorations. On the other hand, patients under active surveillance, IMRT, and real-time brachytherapy showed a moderate improvement in mental health. It is important to consider each patient’s preferences regarding their treatment strategy, with personalized information about the potential risks and benefits, during the shared decision-making process.