Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience

Background: The use of intra-fractional monitoring and correction of prostate position with the Image Guided Radio Therapy (IGRT) system can increase the spatial accuracy of dose delivery. Clarity is a system used for intrafraction prostate-motion management, it provides a real-time visualization of prostate with a transperineal ultrasound. The aim of this study was to evaluate the use of Clarity-IGRT on proper intrafraction alignment and monitoring, its impact on Planning Tumor Volume margin and on urinary and rectal toxicity in elderly patients not eligible for surgery. Patients and Methods: Twenty-five elderly prostate cancer patients, median age=75 years (range=75-90 years) were treated with Volumetric Radiotherapy and Clarity-IGRT using 3 different schemes: A) 64.5/72 Gray (Gy) in 30 fractions on prostate and seminal vesicles (6 patients); B) 35 Gy in 5 fractions on prostate and seminal vesicles (12 patients); C): 35 Gy in 5 fractions on prostate (7 patients). Ultrasound identification of the overlapped structures to the detected ones during simulation has been used in each session. A specific software calculates direction and entity of necessary shift to obtain the perfect match. The average misalignment in the three-dimensional space has been determined and shown in a box-plot. Results: All patients completed treatment with mild-moderate toxicity. During treatment, genitourinary toxicity was 32% Grade 1; 4% Grade 2, rectal was 4% Grade 1. At follow-up of 3 months, genitourinary toxicity was 20% Grade 1; 4% Grade 2, rectal toxicity was 4% Grade 2. At follow-up of 6 months, genitourinary toxicity was 4% Grade 1; 4% Grade 2. Rectal toxicity was 4% Grade 2. Conclusion: Radiotherapy with the Clarity System allows a reduction of PTV margins, the amount of fractions can be reduced increasing the total dose, not exacerbating urinary and rectal toxicity with greater patient's compliance.In recent years, several clinical and experimental data have suggested an α/β ratio of 1.5 Gy for prostate cancer and this has encouraged the introduction of hypofractionation in its treatment (1). Prostate cancer α/β ratio seems lower than dose-limiting surrounding tissue of rectum and urinary bladder. The safe dose/fraction escalation improves the therapeutic ratio of prostate cancer radiotherapy, increasing cure rate with reducted toxicity. The α/β ratio for the rectum and bladder is generally assumed to be 3 Gy and 5-10 Gy, respectively. Moderate (dose 2.4-4 Gy) and extreme (dose 6.7-10 Gy) hypofractionation has been investigated in PC over the last decade (2-4). In many reviews and metaanalyzes, the ratio α/β is reported between 1.4 Gy and 1.93 Gy (1,(5)(6)(7)(8).

Section: Discussionsupporting

confidence: 72%

Acute Toxicity in Hypofractionated/Stereotactic Prostate Radiotherapy of Elderly Patients: Use of the Image-guided Radio Therapy (IGRT) Clarity System

Franco

Borzillo

Alberti

et al. 2021

“…Considering that median dose to LN was 46 Gy in the current study, a higher dose to metastatic LNs might be required to achieve a more favorable outcome. In such cases, toxicities related to dose escalation, as have been reported by previous studies, require an additional consideration (21). Alternative measures such as the utilization of brachytherapy may be considered, especially when taking the rectal toxicity into account (22).…”

Section: Discussionmentioning

confidence: 95%

Predictors of Outcomes in Patients With Clinically Lymph Node Positive Prostate Cancer After Definitive Radiotherapy

KIM,

KIM

2023

Background/Aim: Studies have suggested that benefits of definitive radiotherapy might be limited to specific patients in clinically lymph node positive (cN1) prostate cancer (PC). However, the beneficial subgroup remains to be elucidated. This study aimed to analyze survival outcomes and prognostic factors after definitive radiotherapy and androgen deprivation therapy (definitive RT+ADT) in these patients and to define subgroups of patients who would benefit from definitive RT+ADT the most. Patients and Methods: A total of 60 patients with cN1 PC treated with definitive RT+ADT in a single tertiary hospital were accrued. Their clinicopathological variables were analyzed and a new subgroup was identified based on statistically significant variables. Results: At a median follow-up of 31 months, ADT duration ≥24 months (p=0.043, HR=0.26) and positive biopsy core ≥75% (p=0.044, HR=5.29) showed significant relationships with distant metastasis-free survival. Overall survival showed significant relationships with ADT duration ≥24 months (p=0.002, HR=0.06) and number of lymph node (LN) metastases ≥4 (p=0.019, HR=7.17). For prognostic subgroup analysis, patients were divided into three risk groups: low-risk group (LN metastases <4 and ADT ≥24 months), high-risk group (LN metastases ≥4 and ADT <24 months), and intermediaterisk group (all remaining cases). Three-year actuarial overall survival rates for the low-, intermediate-, and highrisk groups were 100%, 93.3%, and 45.7%. Conclusion: ADT duration and number of LN metastases were important prognostic factors in patients with cN1 PC receiving definitive RT+ADT, with low-risk cN1 PC patients showing better outcomes than others.Although patients with clinically lymph node (LN) positive (cN1) prostate cancer (PC) account for 13% of patients with newly diagnosed PC, no randomized clinical trial has been conducted to establish a solid evidence-based treatment (1). The most widely accepted treatment to date is androgen deprivation therapy (ADT). However, systematic review and population based cohort studies have shown that ADT combined with local therapy is associated with significantly improved survival in these patients (2, 3). In addition, some studies have suggested that radiotherapy (RT) could serve as an effective local therapy option (4, 5). One study analyzing National Cancer Database (NCDB) data has found that ADT combined with RT can increase the 5-year overall survival (OS) rate by 20% for these patients (5).However, extrapolating from research on pathologically LN positive (pN1) PC, such therapeutic gain might be limited to a specific subgroup of patients with cN1 PC. A prior study investigating patients with pN1 PC has confirmed that benefits of RT are limited to a newly defined intermediate risk group established based on criteria using number of LN metastases, Gleason score, and pathologic T stage (6, 7). Meanwhile, several studies analyzing patients with cN1 PC receiving definitive RT and ADT have also revealed unfavorable prognostic factors. Lilleby et al. h...

“…All these findings support a dose delivery to the prostate ≥74 Gy for a theoretical better local control. However, the usefulness of such a prescription is questioned by the works of Meng and Lee et al(30,31) that did not show a therapeutic gain with escalated doses, intended as prolongation of overall and biochemical recurrence free survival, but only a higher rate of moderate-severe rectal toxicity. Clinical Target Volume (CTV) delineation on Magnetic Resonance (MR) images did not reduce the risk of proctitis, but only urinary disorders according to Sander et al(32).…”

mentioning

confidence: 99%

A Ten-year-long Update on Radiation Proctitis Among Prostate Cancer Patients Treated With Curative External Beam Radiotherapy

Ferini¹,

Pergolizzi

2021

This comprehensive synopsis summarizes the most relevant information obtained from a systematic analysis of studies of the last decade on radiation proctitis, one of the most feared radioinduced side effects among prostate cancer patients treated with curative external beam radiotherapy. The present review provides a useful support to radiation oncologists for limiting the onset or improving the treatment of radiation proctitis. This work shows that the past decade was a harbinger of significant new evidence in technological advances and technical tricks to avoid radiation proctitis, in addition to dosimetric perspectives and goals, understanding of pathogenesis, diagnostic work-up and treatment. We believe that a well-rounded knowledge of such an issue is fundamental for its appropriate management.