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Thread: (K) Post-Treatment PSA BCR Adjuvant & Salvage RT

  1. #191
    Prostate-Specific Membrane Antigen PET/Magnetic Resonance Imaging for the Planning of Salvage Radiotherapy in Patients with Prostate Cancer with Biochemical Recurrence After Radical Prostatectomy
    [2019, Review, Full Text]


    This article presents an overview of the current literature on PET imaging with prostate-specific membrane antigen ligands, especially focusing on the potential role of simultaneous PET/magnetic resonance imaging for the planning of salvage radiotherapy in patients with prostate cancer with biochemical recurrence after radical prostatectomy.
    From the Full Text:

    Key Points
    • Prostate-specific membrane antigen (PSMA) PET/magnetic resonance (MR) imaging can help distinguish between patients with prostate cancer with locoregional recurrence and those with distant metastases, even at low prostate-specific antigen levels.
    • PSMA PET/MR imaging may have advantages compared with PET/computed tomography for the detection of local recurrence and anatomic correlates to PET-positive lymph node and bone lesions.
    • PSMA PET/MR imaging can help in making informed treatment decisions in patients with biochemical recurrence after radical prostatectomy.
    • PSMA PET/MR imaging enables dose-escalated and metastases-directed salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy.

    sRT is a potentially curative treatment option for patients with prostate cancer with BCR after RP, especially when PSA levels are still low. Because of a lack of sensitive conventional imaging methods, the planning of sRT is currently being performed in the absence of visual evidence of the site of recurrence. Simultaneous PSMA PET/MR imaging combines excellent soft tissue contrast with a superior sensitivity for cancer, and can help detect recurrence in the prostate bed, lymph nodes, bones, and distant organs. Consequently, PSMA PET/MR imaging can play an important role in the selection of patients who may benefit from sRT, and facilitate dose-escalated and metastases-directed treatment planning. Whether or not PSMA PET/MR imaging–based planning of sRT can improve the long-term outcome in patients with BCR after RP should be answered in prospective randomized controlled trials.

  2. #192
    Smoking history, intensity, and duration and risk of prostate cancer recurrence among men with prostate cancer that received definitive treatment



    To examine the association of smoking history and multiple measures of smoking intensity and duration with risk of biochemical recurrence in men treated for prostate cancer.

    We conducted a prospective cohort study of 1641 men (773 ever-smokers) treated with radical prostatectomy or radiation between 2003-2010. The association between ever-smoking and risk of biochemical recurrence was examined using Cox Proportional Hazards models with adjustment for confounders. Among ever-smokers, we further assessed the association between multiple measures of smoking duration and intensity and risk of biochemical recurrence.

    In the full cohort, we observed no association between ever-smoking and risk of biochemical recurrence. However, among ever-smokers a smoking duration of ≥ 10 years was significantly associated with biochemical recurrence (Hazard Ratio (HR): 2.32, 95% Confidence Interval (CI): 1.01, 5.33). Our results also suggested that ≥ 10 pack-years of smoking may be associated with an increased risk of biochemical recurrence (HR: 1.75, 95% CI: 0.97, 3.15). No association was observed between packs smoked per day or years since smoking cessation (among former smokers) and risk of biochemical recurrence.

    Smoking duration is a significant predicator of biochemical recurrence among men with prostate cancer who are current or former smokers.

  3. #193

  4. #194
    Natural history of ‘second’ biochemical failure after salvage radiation therapy for prostate cancer: a multi‐institution study
    [2017, Full Text]



    To describe the natural history of prostate cancer in men who experience a second biochemical recurrence (BCR) after salvage radiotherapy (SRT) after prostatectomy.

    Patients and Methods
    After undergoing SRT at one of two institutions between 1986 and 2013, 286 patients experienced a second BCR, defined as two rises in prostate‐specific antigen (PSA) of ≥0.2 ng/mL above nadir. Event rates for distant metastasis (DM) or freedom from DM (FFDM), castration‐resistant prostate cancer (CRPC), prostate cancer‐specific survival (PCSS), and overall survival (OS) were estimated using the Kaplan–Meier method. Cox regression was used for comparative analyses.

    At a median of 6.1 years after second BCR, DM, CRPC, PCSS and OS rates were 41%, 27%, 83% and 73%, respectively. On multivariable analysis, interval to second BCR <1 year (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.71–4.14; P < 0.001], Gleason score 8–10 (HR 1.65, 95% CI 1.07–2.54; P = 0.022), and concurrent ADT during SRT (HR 1.76, 95% CI 1.08–2.88; P = 0.024) were associated with FFDM, while PCSS was associated with interval to second BCR <1 year (HR 3.00, 95% CI 1.69–5.32; P < 0.001) and concurrent ADT during SRT (HR 2.15, CI 1.13–4.08; P = 0.019). These risk factors were used to stratify patients into three groups, with 6‐year FFDM rates of 71%, 59% and 33%, and PCSS rates of 89%, 79%, and 65%, respectively.

    Following second BCR after SRT, clinical progression is enriched in a subgroup of patients with prostate cancer, while others remain without DM for long intervals. Stratifying patients into risk groups using prognostic factors may aid counselling and future trial design.

  5. #195
    Salvage brachytherapy for locally-recurrent prostate cancer after radiation therapy: A comparison of efficacy and toxicity outcomes with high-dose rate and low-dose rate brachytherapy



    Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques.

    Methods and materials
    Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale.

    Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%–75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy <30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients.

    These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

  6. #196
    Adjuvant or salvage radiotherapy for the treatment of localised prostate cancer? A prospectively planned aggregate data meta-analysis


    Three randomised trials, RADICALS (ISRCTN40814031), GETUG-AFU 17 (NCT00667069) and RAVES (NCT00860652), have compared adjuvant radiotherapy (ART) with a policy of salvage radiotherapy for PSA failure (SRT) after radical prostatectomy for men with localised prostate cancer, but have limited power for long-term outcomes. Therefore, the ARTISTIC collaboration prospectively planned a series of meta-analyses for each outcome.

    Using a framework for adaptive meta-analysis (FAME), we prospectively defined our methods, including a consistent definition of PSA-driven event-free survival (EFS), prior to knowledge of trial results (CRD42019132669). We anticipated 240 events across all trials by Autumn 2019, giving 90% power to detect a 5% absolute difference in 5-year EFS. This provided a firm basis for a meta-analysis at this time.

    Across the 3 trials, 1074 men were randomised to ART and 1077 to SRT. To date, 395 men (37%) had commenced SRT. Patient characteristics were balanced within trials and overall. Men had median age of 65 years and most (77%) had a Gleason sum score of 7. Median follow-up ranged from 47 to 61 months. In August 2019, RADICALS and GETUG-AFU 17 provided EFS results for the meta-analysis (interim for GETUG-AFU 17). RAVES currently could only supply freedom from biochemical failure results. However, as the vast majority of first events across all trials are biochemical failures, these results have been pooled in a preliminary meta-analysis of EFS. Based on 245 events, the meta-analysis shows no evidence that EFS is improved with ART compared to SRT (HR = 1.09, 95% CI = 0.86-1.39, p = 0.47). This translates to a potential absolute difference of 1% at 5 years in favour of SRT (95% CI: 2% in favour ART to 4% in favour of SRT).

    This collaborative, prospective and early meta-analysis of all men from 3 randomised trials, suggests that SRT and ART offer similar outcomes for EFS. However, SRT spares many men from receiving RT, and associated side-effects. Final data from GETUG-AFU 17 and RAVES may help establish whether some subgroups of men might benefit from either treatment. Longer follow-up is needed for a meta-analysis of metastasis-free survival.

  7. #197
    Overall survival (OS) and metastasis-free survival (MFS) in men with biochemically relapsed (BCR) prostate cancer after radical prostatectomy (RP) managed with deferred androgen deprivation treatment (ADT): A combined Johns Hopkins and CPDR study



    ADT prior to mets may not improve QoL or OS in BCR prostate cancer and may result in irreversible adverse events at high costs. Early use of novel androgen receptor targeting drugs (NARTD) prolonged MFS in nonmetastatic-castration resistant prostate cancer (nmCRPC). However, clinical details prior to castration resistance and explicit criteria for starting ADT were not given. We hypothesize that deferring ADT until mets results in outcomes comparable to those reported with early ADT, irrespective of NARTD used in nmCRPC.

    Retrospective review of men who underwent RP from1983 - 2014 within Johns Hopkins and the Center for Prostate Disease Research Multi-Center National Database, developed BCR and did not receive ADT until metastasis. Kaplan-Meier estimates of MFS and OS were defined from RP to event/last follow-up. Multivariable Cox proportional hazard models identified predictive factors.

    2,930 men fulfilled eligibility criteria: median age 61,17% African American, Gleason 6 (29%),7 (52%), 8-10 (18%), + margins 38%, median PSADT 27 mos. With a median F/U of 10 years, 20% developed M+ and received ADT, 27% died. Median MFS was 24 yrs (21-27 yrs) and median OS was 21 yrs (20-22 yrs) (Table). Age at surgery, pT stage, Gleason sum, surgical margin status and PSADT significantly predicted OS (p<.03). pT stage, Gleason sum, time to BCR, race and PSADT predicted MFS (p < 0.01).

    [See Table]

    Deferred ADT until time of metastases results in long MFS and OS even with short PSADT suggesting that it remains possible that prolongation of MFS in nmCRPC may not reflect true overall net therapeutic benefits which requires prospective study to define specific patient selection and criteria for initial ADT implementation, control of post progression management and QoL/OS information.


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