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Thread: (O) Locally Advanced Prostate Cancer

  1. #21
    Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations
    [2017, Full Text]



    The oligometastatic state has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastases. With improvements in diagnostic modalities such as functional imaging, oligometastatic prostate cancer is being diagnosed with greater frequency than ever before. Furthermore, the paradigm for treatment of advanced prostate cancers is shifting toward a more aggressive approach. Many questions surround the understanding of the process and consequences of oligometastasis, meaning that the contemporary literature offers a wide variety of definitions of oligometastatic prostate cancer. Until genomic data exist to provide a biological component to the definition of oligometastatic disease, a clinical diagnosis made on the basis of up to five extrapelvic lesions is reasonable for use. Retrospective studies suggest that interventions such as radical prostatectomy and local or metastasis-directed radiotherapy can be performed in the metastatic setting with minimal risk of toxic effects. These therapies seem to decrease the need for subsequent palliative interventions, but insufficient data are available to draw reliable conclusions regarding their effect on survival. Thus, a protocol for clinicians to manage the patient presenting with oligometastatic prostate cancer would be a useful clinical tool.

  2. #22
    Treatment of Oligometastatic Hormone-Sensitive Prostate Cancer: A Comprehensive Review
    [2018, Full Text]



    With advancements in diagnostic techniques, including molecular and clinical imaging, that directly target cancer cells, oligometastatic prostate cancer (PCa) is being diagnosed in patients who were, in the past, considered to have localized disease. With accumulating evidence, there has been a paradigm shift in considering aggressive treatments targeted at both the primary tumor and metastatic lesions in an aim to avoid and delay the need for palliative treatments and, ultimately, to achieve survival benefits. However, many questions still remain unanswered regarding the understanding of oligometastatic PCa, from its definition to optimal treatment strategies for each individual. Limited retrospective studies have suggested that interventions, including local and/or metastasis-directed therapy using surgery and radiation therapy (RT), can improve survival outcomes with minimal risk of adverse effects. Such treatments have been shown to decrease the risks of subsequent palliative interventions and to delay the start of androgen-deprivation therapy. Nevertheless, available data are insufficient to draw a reliable conclusion regarding their effect on quality of life measures and overall survival. This comprehensive review overviews data from contemporary literature that have investigated treatments, including surgery and RT, for patients with oligometastatic PCa, namely pelvic lymph node positive disease and limited distant metastases, and summarizes ongoing trials that are evaluating the feasibility of aggressive multimodal treatments.

  3. #23
    Survival outcomes of locally advanced prostate cancer in patients aged < 50 years after local therapy in the contemporary US population



    To assess survival outcomes of locally advanced prostate cancer (LAPC) in patients aged < 50 years after local therapy (LT), as compared to that in the older patients (≥ 50 years). Moreover, effectiveness of postoperative radiation therapy (PRT) after radical prostatectomy (RP) was also assessed in patients aged < 50 years.


    Within the Surveillance, Epidemiology, and End results database (2004–2014), non-metastatic cT3–4 LAPC patients treated with LT (RP, RT or RP+RT) were identified. After propensity score matching (PSM), cancer-specific mortality (CSM), overall survival (OS), and other-cause mortality (OCM) rates were assessed. Multivariable competing risk regression (MVA CRR) model was also used in our analysis.

    1507 younger (< 50 years) and 34833 older (≥ 50 years) LAPC patients treated with LT were identified. Younger patients with LAPC had overall more aggressive disease features than their older counterparts. After PSM, younger patients yielded higher cumulative CSM rates than the older patients (P = 0.046). However, OS and cumulative OCM rates were significantly higher (P = 0.038 and P < 0.0001, respectively) in the older cohort. In the MVA CRR model, younger patients yielded higher CSM (P = 0.02). Specifically, younger patients resulted in higher CSM in Gleason score 8–10, cT3b/4 stage, cN1 stage, and patients treated with RP. No statistically significant differences were found in patients treated with RP versus RP+PRT in all parameters.

    LAPC patients aged < 50 years yielded higher CSM after LT, specifically after RP, compared with the older counterparts (≥ 50 years). No significant differences were observed in RP versus RP+PRT regarding survival outcomes in our analysis.

  4. #24



    To evaluate the comparative effectiveness of local versus systemic therapy among patients diagnosed with non-metastatic clinical T4 prostate cancer.

    Using the National Cancer Database (NCDB) men with clinical T4N0-1M0 prostate cancer from 2004 to 2013 were identified. Local therapy was defined as radiation (RT with ADT), surgery (radical prostatectomy with ADT), or combined radiation plus surgery (radical prostatectomy plus RT with ADT). Systemic therapy was defined as ADT or chemotherapy alone. The primary outcome of overall survival was estimated using the Kaplan Meier method. Factors associated with overall survival were determined by Cox proportional hazards models.

    A total of 1,914 patients were included in our analysis, 1,559 received local therapy and 355 received systemic therapy. Median 5-year survival for local versus systemic therapy was 41.5 and 28.2 months, respectively. On multivariable analysis, local therapy was associated with increased overall survival compared to systemic therapy (HR=0.52; 95%CI, 0.44-0.62, p<0.001). Comparing local therapy treatment modalities, both radiation (HR=0.44; 95%CI, 0.36-0.53, p<0.001) and surgery (HR=0.67; 95%CI, 0.55-0.82, p<0.001) were associated with increased overall survival compared to systemic therapy. Among those receiving local therapy, more patients were treated with radiation (n=709/1559 or 45.5%) compared to surgery (n=560/1559 or 35.9%) or combined radiation plus surgery (n=290/1559 or 18.6%) with 5-year overall survival by treatment type being 61%, 51.4% and 62.2%, respectively.

    Local therapy for clinical T4 prostate cancer is associated with improved overall survival. Due to the retrospective, non-randomized nature of the study design, a clinical trial is needed to better define the efficacy of local therapy in this high-risk patient population.

  5. #25
    Impact of Adjuvant Radiotherapy in Node-positive Prostate Cancer Patients: The Importance of Patient Selection



    Using institutional data, we have previously developed an algorithm to identify the optimal candidates for adjuvant radiotherapy (aRT) among men with pN1 prostate cancer (PCa) at radical prostatectomy (RP). This study aimed to test the external validity of our previous findings using a nationwide database while focusing on overall mortality as an endpoint. To this end, we identified 5498 pN1 PCa patients who were treated with RP, pelvic lymph node dissection, and androgen deprivation therapy with or without aRT, within the National Cancer Database, between 2004 and 2015. Patients were divided into five groups based on our previously published algorithm. Similar to our previous report, multivariable Cox regression analysis showed that only two of these groups benefit from aRT: (1) those with one to two positive nodes, pathological Gleason score 7–10, and pT3b/4 disease or positive surgical margins (hazard ratio [HR] = 0.75); and (2) those with three to four positive nodes, regardless of local tumor characteristics (HR = 0.57, both p = 0.01). In the remaining patients (25% of the cohort), aRT had no significant survival benefit. Results were confirmed on sensitivity analyses using 1:1 propensity score-matched cohorts, excluding men who died within 3 yr of surgery and using cut-off of 6 mo post-surgery to identify receipt of aRT. Our findings corroborate the validity of our previously published criteria and highlight the importance of patient selection in pN1 PCa patients who are considered for aRT.

  6. #26
    Local ablative stereotactic body radiotherapy for oligometastatic prostate cancer



    The oligometastases is considered an intermediate state of the disease between localized and wide spread metastases. Local ablative therapy to oligometastatic prostate cancer is gaining significant traction and stereotactic body radiotherapy (SBRT) is an emerging treatment modality for this patient population. In this review, we report our literature review of SBRT to prostate oligometastases. Current evidence on the role of SBRT in oligometastatic prostate cancer reported in the last 10 years was summarized. Criteria for inclusion included studies with prostate cancer only as the primary site.

    The unique properties of the oligometastatic prostate cancer appear to carry a better prognosis than wide spread metastatic disease, especially if these metastases are amenable to local ablative therapies. Our literature review revealed that local ablative therapy, using SBRT to prostate oligometastases, is associated with significant 2-years local control and acceptable toxicity profile.

    SBRT to oligometastatic prostate cancer patients is feasible and carries an acceptable toxicity profile. The randomized phase II and III trials, currently underway, should clearly define the real benefit of this approach on progression-free and overall survival outcomes.

  7. #27
    Will Image-guided Metastasis-directed Therapy Change the Treatment Paradigm of Oligorecurrent Prostate Cancer?
    [2018, Full Text]


    Take Home Message

    Although recent studies support the role of image-guided metastasis-directed therapies in the oligo-recurrent setting, several issues including the risk of possible underestimation of the true tumor burden at imaging, patient selection and the lack of studies comparing different approaches limit their implementation in the clinical practice. As such, metastasis-directed therapies should still be considered as investigational treatment options in oligo-recurrent prostate cancer patients.
    [Emphasis mine]

  8. #28
    Non-metastatic castration resistant prostate cancer: a review of current and emerging medical therapies
    [Review 2018]



    Non-metastatic castration resistant prostate cancer (M0CRPC) is a heterogenous disease state affecting an estimated 100,000 men in the United States. Development of more sensitive modalities for detection of metastasis has altered the landscape of advanced prostate cancer, but M0CRPC has remained a condition that previously lacked FDA-approved treatment. The emerging data on new generation Androgen Receptor (AR) pathway inhibitors should address this gap in the management of such patients.

    We reviewed and summarized the current literature for the definition, diagnosis and treatment of M0CRPC. We highlight the results of recent Phase III trials that show significant impact on the outcomes of M0CRPC.

    Androgen deprivation therapy remains the foundation of therapy for M0CRPC. Recently published Phase III trials provided data on improved progression free survival when ADT is augmented with newer AR pathway inhibitors. The SPARTAN trial showed that metastasis-free survival (MFS) for patients treated with apalutamide plus ADT is 40.5 months compared to 16.2 months for patients who received standard ADT plus placebo, a 72% reduction in the risk of distant metastasis or death in apalutamide plus ADT compared to ADT plus placebo. The PROSPER trial demonstrated that MFS for patients treated with enzalutamide plus ADT was 36.6 months compared to 14.7 months for patients who received standard ADT only indicating a 71% reduction in the risk of developing metastatic CRPC or death compared to ADT alone. The ARAMIS trial on darolutamide, another AR pathway inhibitor, is also ongoing, and can potentially be another fitting option for M0CRPC.

    The recent Phase III trials SPARTAN and PROPSER demonstrate effective treatment options for the M0CRPC disease state that has historically lacked treatment from high level evidence. In particular, an FDA-approved treatment, Apalutamide, can finally be offered for M0CRPC patients. The newer AR pathway inhibitors should provide a basis for further investigation into treatments for M0CRPC.

  9. #29
    Node-positive Nonmetastatic Prostate Cancer: Time to Reconsider Prognostic Staging?
    [2018, Full Text]



    Take Home Message

    Node-positive nonmetastatic prostate cancer is currently prognosticated as stage IV, despite evidence that a proportion of this patient population can be cured. We provide evidence and request reconsideration of prognostic staging in the next edition of the American Joint Committee on Cancer staging manual.
    From the Full Text:

    From this national data set, approximately one-third of patients with N1M0 prostate cancer are not receiving definitive therapy for their disease, which is probably partly driven by the stage IV designation for this patient population. Classification as stage IV also adds unnecessary anxiety for patients and their caregivers given the association of stage IV with incurable disease. Improved survival among N1M0 compared to M1 patients was maintained on multivariate analysis controlling for confounders such as differences in the rates of definitive local treatment. Given the survival outcomes and cure rates observed in this patient population, we feel that the stage IV designation for N1M0 prostate cancer should be re-evaluated.

  10. #30
    Worth a local treatment? – Analysis of modern radiotherapy concepts for oligometastatic prostate cancer
    [2018, Full Text]



    Prostate cancer (PCA) is the most-prevalent non-skin cancer in men worldwide. Nevertheless, the treatment of oligometastatic, especially lymph-node (ln) recurrent, PCA remains elusive. The aim of our study was to provide insights in radiotherapy (RT)-treatment of recurrent PCA exhibiting ln- or osseous (oss)-oligometastases.

    Between April 2012 and April 2017, 27 oligometastatic PCA patients (19 ln and 8 single oss) were treated with RT at our institution.

    The metastasis-free survival (MFS) was 24.8 m (22.0–36.0 m) and 25.4 m (23.9–28.1 m) for the ln- and oss-subgroup resulting in 1-year MFS of 75.4 and 100% and 2-year MFS of 58.7 and 83.3% for ln- and oss-metastatic patients, respectively. Of notice, none of the recurrences for ln-patients was in the RT-field, constituting a local control of 100%.

    Within the ln-group, pre-RT median-PSA was 2.6 ng/ml, median post-RT PSA was 0.3 ng/ml, which was significant (p = 0.003). Median biochemical-free survival (bfS) was 12.2 m. PCA that was initially confined to the prostate had a better bfS (p < 0.001) and MFS (p = 0.013). The oss-group had a median PSA of 4.9 ng/ml pre-treatment which dropped to a median value of 0.14 ng/ml (p = 0.004).

    Toxicities were moderate, with only 1 case of III° toxicity. There were no deaths in the ln-group, thus overall survial was 100% here.

    Our study points out the feasibility of RT as a treatment option in recurrent PCA and demonstrates an excellent local control with a low-toxicity profile.


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