scholarly journals Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?

2021 ◽  
Vol 11 ◽  
Author(s):  
Nicolas Giraud ◽  
Nicolas Benziane ◽  
Ulrike Schick ◽  
Jean-Baptiste Beauval ◽  
Ahmad Chaddad ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Specific Antigen ◽  
Late Toxicity ◽  
Free Survival ◽  
Conventional Fractionation ◽  
Cardiovascular Comorbidities ◽  
Prostate Bed ◽  
Prostate Cancers ◽  
The Cost ◽  
New Generation

Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64–66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.

The acute toxicity results of the GETUG-AFU 22 study: A multicenter randomized phase II trial comparing the efficacy of a short hormone therapy in combination with radiotherapy to radiotherapy alone as a salvage treatment for patients with detectable PSA after radical prostatectomy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 16-16 ◽  
Author(s):  
Stephane Gilles Guerif ◽  
Igor Latorzeff ◽  
Lise Roca ◽  
Djelila Allouache ◽  
Stephane Supiot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Acute Toxicity ◽  
Hormone Therapy ◽  
Primary Endpoint ◽  
Late Toxicity ◽  
Localized Prostate Cancer ◽  
Free Survival ◽  
Prostate Bed ◽  
Grade 3

16 Background: Radical prostatectomy (RP) is recommended as a standard treatment for localized prostate cancer. However no recommendations exist for pts with detectable PSA after RP. Methods: Pts with localized prostate cancer, treated by RP (R0 or R1), with a PSA level post-RP ≥ 0.2 ng/mL and ≤ 2 ng/mL at randomization and N0 M0 on imaging were included. Pts were randomized (1:1) to radiotherapy (RT) alone (RT arm) or 6 months degarelix hormone therapy (HT) with RT (RT+HT arm). RT consisted of pelvic irradiation (46 Gy in 23 Fr) with a boost on the prostate bed (66 Gy in 33 Fr). The primary endpoint is the event-free survival (EFS). Secondary endpoints are: 5-yr EFS and metastases-free survival, 5 and 10-yr OS, acute and late toxicity (CTCAE V4.0), and QOL. With 122 patients, the probability of selecting the most effective arm is over 80% for a 20% reduction in the HR = 0.80. Results: From Dec-2012 to Sept-2015, 125 pts were included (RT arm: 64 pts; RT+HT arm: 61). Median follow up is 14.7 months (6.2; 33.5). The baseline characteristics are well-balanced: median age was 66 yrs (50-77), all men having an ECOG ≤ 1 (ECOG 0 in 92%), a median Gleason score of 7 (3-9), a median PSA of 0.3 ng/mL (0.09-1.82) post-RP and 0.6 ng/mL (0.12-3.65) at randomization. All pts received 33 Fr of RT. In the RT+HT arm 98.4% of pts received the 6 months of HT planned. All pts were eligible for safety analysis. No grade 4 toxicity or toxic death was reported. Grade 3 acute toxicity, occurring within 6 months of RT, were reported for 11/125 pts (9%): 3/64 pts (5%) in the RT arm and 8/61 pts (13%) in RT+HT arm (NS). Regarding grade 3 toxicities, the following occurred only in the RT+HT arm: erectile dysfunction (3 pts) and urinary incontinence (2 pts); in contrast, dysuria/pollakiuria (2 pts) occurred only in the RT arm. In the RT+HT arm, grade 2 toxicities included hot flushes (8 pts) and decreased libido (7 pts). Conclusions: In terms of acute toxicities the RT+HT arm is well tolerated with the observed toxicities usually expected with concomitant HT. The primary endpoint analysis is expected for 2018. Clinical trial information: NCT01994239.

Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer

2017 ◽  
Vol 35 (17) ◽  
pp. 1884-1890 ◽  
Author(s):  
Charles N. Catton ◽  
Himu Lukka ◽  
Chu-Shu Gu ◽  
Jarad M. Martin ◽  
Stéphane Supiot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
Late Toxicity ◽  
Hazard Ratio ◽  
Localized Prostate Cancer ◽  
Intermediate Risk ◽  
Conventional Fractionation ◽  
Distant Failure ◽  
Risk Prostate Cancer

Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.

scholarly journals Feasibility and Outcome of PSMA-PET-Based Dose-Escalated Salvage Radiotherapy Versus Conventional Salvage Radiotherapy for Patients With Recurrent Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Marco M. E. Vogel ◽  
Sabrina Dewes ◽  
Eva K. Sage ◽  
Michal Devecka ◽  
Kerstin A. Eitz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pet Imaging ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
Late Toxicity ◽  
Salvage Radiotherapy ◽  
Stool Incontinence ◽  
Prostate Bed ◽  
Psma Pet ◽  
Psa Response

IntroductionProstate-specific membrane antigen-positron emission tomography-(PSMA-PET) imaging facilitates dose-escalated salvage radiotherapy (DE-SRT) with simultaneous-integrated boost (SIB) for PET-positive lesions in patients with prostate cancer (PC). Therefore, we aimed to compare toxicity rates of DE-SRT with SIB to conventional SRT (C-SRT) without SIB and to report outcome.Materials and MethodsWe evaluated 199 patients who were treated with SRT between June 2014 and June 2020. 101 patients received DE-SRT with SIB for PET-positive local recurrence and/or PET-positive lymph nodes. 98 patients were treated with C-SRT to the prostate bed +/− elective pelvic lymphatic pathways without SIB. All patients received PSMA-PET imaging prior to DE-SRT ([68Ga]PSMA-11: 45.5%; [18F]-labeled PSMA: 54.5%). Toxicity rates for early (&lt;6 months) and late (&gt;6 months) gastrointestinal (GI) toxicities rectal bleeding, proctitis, stool incontinence, and genitourinary (GU) toxicities hematuria, cystitis, urine incontinence, urinary obstruction, and erectile dysfunction were assessed. Further, we analyzed the outcome with disease-free survival (DFS) and prostate-specific antigen (PSA) response.ResultsThe overall toxicity rates for early GI (C-SRT: 2.1%, DE-SRT: 1.0%) and late GI (C-SRT: 1.4%, DE-SRT: 5.3%) toxicities ≥ grade 2 were similar. Early GU (C-SRT: 2.1%, DE-SRT: 3.0%) and late GU (C-SRT: 11.0%, DE-SRT: 14.7%) toxicities ≥ grade 2 were comparable, as well. Early and late toxicity rates did not differ significantly between DE-SRT versus C-SRT in all subcategories (p&gt;0.05). PSA response (PSA ≤0.2 ng/ml) in the overall group of patients with DE-SRT was 75.0% and 86.4% at first and last follow-up, respectively.ConclusionDE-SRT showed no significantly increased toxicity rates compared with C-SRT and thus is feasible. The outcome of DE-SRT showed good results. Therefore, DE-SRT with a PSMA-PET-based SIB can be considered for the personalized treatment in patients with recurrent PC.

scholarly journals Extraperitoneal Robotic Laparo-Endoscopic Single-Site Plus1-Port Radical Prostatectomy Using the da Vinci Single-Site Platform

2021 ◽  
Vol 10 (8) ◽  
pp. 1563
Author(s):  
Ching-Chia Li ◽  
Tsu-Ming Chien ◽  
Ming-Ru Lee ◽  
Hsiang-Ying Lee ◽  
Hung-Lung Ke ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Da Vinci ◽  
Specific Antigen ◽  
Operation Time ◽  
Setup Time ◽  
Single Site ◽  
University Hospital ◽  
Da Vinci Surgical System ◽  
Free Survival ◽  
The Aesthetic

Currently, over 80% of radical prostatectomies have been performed with the da Vinci Surgical System. In order to improve the aesthetic outlook and decrease the morbidity of the operation, the new da Vinci Single Port (SP) system was developed in 2018. However, one major problem is the SP system is still not available in most countries. We aim to present our initial experience and show the safety and feasibility of the single-site robotic-assisted radical prostatectomy (LESS-RP) using the da Vinci Single-Site platform. From June 2017 to January 2020, 120 patients with localized prostate cancer (stage T1–T3b) at Kaohsiung Medical University Hospital were included in this study. We describe our technique and report our initial results of LESS-RP using the da Vinci Si robotic system. Preoperative, intraoperative and postoperative patient variables were recorded. Prostate-specific antigen (PSA)-free survival was also analyzed. A total of 120 patients were enrolled in the study. The median age of patients was 68 years (IQR 63–71), with a median body mass index of 25 kg/m2 (IQR 23–27). The median PSA value before operation was 10.7 ng/mL (IQR 7.9–21.1). The median setup time for creat-ing the extraperitoneal space and ports document was 25 min (IQR 18–34). The median robotic console time and operation time were 135 min (IQR 110–161) and 225 min (IQR 197–274), respectively. Median blood loss was 365 mL (IQR 200–600). There were 11 (9.2%) patients who experienced complications (Clavien–Dindo classification Gr II). The me-dian catheter duration was 8 days (IQR 7–9), with a median of 10 days (IQR 7–11) of hospital stay. The PSA free-survival rate was 86% at a median 19 months (IQR 6–28) of follow up. Robotic radical prostatectomy using the da Vinci Single-Site platform system is safe and feasible, with acceptable outcomes.

scholarly journals Clinical diagnosis of prostate cancer using digital rectal examination and prostate-specific antigen tests: a systematic review and meta-analysis of sensitivity and specificity

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Nelson C. Okpua ◽  
Simon I. Okekpa ◽  
Stanley Njaka ◽  
Augusta N. Emeh
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Antigen Test ◽  
Rectal Examination ◽  
Prostate Specific Antigen Test ◽  
Prostate Cancers ◽  
Antigen Tests

Abstract Background Being diagnosed with cancer, irrespective of type initiates a serious psychological concern. The increasing rate of detection of indolent prostate cancers is a source of worry to public health. Digital rectal examination and prostate-specific antigen tests are the commonly used prostate cancer screening tests. Understanding the diagnostic accuracies of these tests may provide clearer pictures of their characteristics and values in prostate cancer diagnosis. This review compared the sensitivities and specificities of digital rectal examination and prostate-specific antigen test in detection of clinically important prostate cancers using studies from wider population. Main body We conducted literature search in PubMed, Medline, Science Direct, Wiley Online, CINAHL, Scopus, AJOL and Google Scholar, using key words and Boolean operators. Studies comparing the sensitivity and specificity of digital rectal examination and prostate-specific antigen tests in men 40 years and above, using biopsy as reference standard were retrieved. Data were extracted and analysed using Review manager (RevMan 5.3) statistical software. The overall quality of the studies was good, and heterogeneity was observed across the studies. The result comparatively shows that prostate-specific antigen test has higher sensitivity (P < 0.00001, RR 0.74, CI 0.67–0.83) and specificity (P < 0.00001, RR 1.81, CI 1.54–2.12) in the detection of prostate cancers than digital rectal examination. Conclusion Prostate-specific antigen test has higher sensitivity and specificity in detecting prostate cancers from men of multiple ethnic origins. However, combination of prostate-specific antigen test and standardized digital rectal examination procedure, along with patients history, may improve the accuracy and minimize over-diagnoses of indolent prostate cancers.

scholarly journals Recruitment of β-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells

2004 ◽  
Vol 18 (10) ◽  
pp. 2388-2401 ◽  
Author(s):  
David Masiello ◽  
Shao-Yong Chen ◽  
Youyuan Xu ◽  
Manon C. Verhoeven ◽  
Eunis Choi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Nuclear Receptor ◽  
Specific Antigen ◽  
Prostate Cancer Cells ◽  
Prostate Cell ◽  
Nuclear Receptor Corepressor ◽  
Prostate Cancers

Abstract Prostate cancers respond to treatments that suppress androgen receptor (AR) function, with bicalutamide, flutamide, and cyproterone acetate (CPA) being AR antagonists in clinical use. As CPA has substantial agonist activity, it was examined to identify AR coactivator/corepressor interactions that may mediate androgen-stimulated prostate cancer growth. The CPA-liganded AR was coactivated by steroid receptor coactivator-1 (SRC-1) but did not mediate N-C terminal interactions or recruit β-catenin, indicating a nonagonist conformation. Nonetheless, CPA did not enhance AR interaction with nuclear receptor corepressor, whereas the AR antagonist RU486 (mifepristone) strongly stimulated AR-nuclear receptor corepressor binding. The role of coactivators was further assessed with a T877A AR mutation, found in LNCaP prostate cancer cells, which converts hydroxyflutamide (HF, the active flutamide metabolite) into an agonist that stimulates LNCaP cell growth. The HF and CPA-liganded T877A ARs were coactivated by SRC-1, but only the HF-liganded T877A AR was coactivated by β-catenin. L-39, a novel AR antagonist that transcriptionally activates the T877A AR, but still inhibits LNCaP growth, similarly mediated recruitment of SRC-1 and not β-catenin. In contrast, β-catenin coactivated a bicalutamide-responsive mutant AR (W741C) isolated from a bicalutamide-stimulated LNCaP subline, further implicating β-catenin recruitment in AR-stimulated growth. Androgen-stimulated prostate-specific antigen gene expression in LNCaP cells could be modulated by β-catenin, and endogenous c-myc expression was repressed by dihydrotestosterone, but not CPA. These results indicate that interactions between AR and β-catenin contribute to prostate cell growth in vivo, although specific growth promoting genes positively regulated by AR recruitment of β-catenin remain to be identified.

Phase III study of local or systemic therapy INtensification DIrected by PET in prostate CAncer patients with post-prostaTEctomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5098-TPS5098
Author(s):  
Neha Vapiwala ◽  
Yu-Hui Chen ◽  
Steve Y. Cho ◽  
Fenghai Duan ◽  
Christos Kyriakopoulos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systemic Therapy ◽  
Biochemical Recurrence ◽  
Radiographic Progression ◽  
Systemic Treatment ◽  
Phase Iii ◽  
Type I ◽  
Treatment Intensification ◽  
Free Survival ◽  
Prostate Bed

TPS5098 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given PET's greater sensitivity and specificity, its findings are increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of the otherwise non-tailored SOC approach. Improved systemic control and disease detection with molecular imaging have led to increasing use of focally ablative metastasis-directed RT, to delay or enhance systemic therapy through increased local control. There is also interest in earlier use of systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castration-resistant and metastatic castration-sensitive PC. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA>0.5ng/mL; >0.2ng/mL if within 12 mos of RP) and no metastases on CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes with STAD) are eligible. Prior to study registration, pts undergo SOC baseline PET (18F-fluciclovine but PSMA radiotracers permitted pending commercial availability). Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- metastasis-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of metastasis-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified log-rank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Clinical trial information: NCT04423211.

Sign in / Sign up

Export Citation Format

Share Document