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Thread: (O) Locally Advanced Prostate Cancer

  1. #31
    [#27]
    Survival and secondary interventions following treatment for locally-advanced prostate cancer
    [2018]

    https://www.ncbi.nlm.nih.gov/pubmed/30281010

    Abstract

    INTRODUCTION:
    The utility of radical prostatectomy (RP) for locally-advanced prostate cancer remains unknown. Retrospective data has shown equivalent oncologic outcomes compared to radiation therapy (RT). RP may provide local tumor control and prevent secondary interventions from local invasion, and may decrease costs.

    MATERIALS AND METHODS:
    Using SEER-Medicare data from 1995-2011 we identified men with locally-advanced prostate cancer undergoing RP or RT. Rates of post-treatment diagnoses and interventions were identified using ICD-9 and CPT codes. Skeletal related events (SRE), androgen deprivation therapy (ADT) utilization, all-cause mortality, prostate cancer-specific mortality, and costs were compared.

    RESULTS:
    A total of 8367 men with locally-advanced prostate cancer were identified (6200 RP, 2167 RT). RT was associated with increased urinary obstruction, hematuria, infection, and cystoscopic intervention while RP was associated with increased urethral stricture intervention and erectile dysfunction. Compared to RT, RP was associated with decreased all-cause mortality (3.1 versus 5.2 deaths/100-person-years, p < 0.001), prostate cancer-specific mortality (0.8 versus 2.0 deaths/100-person-years, p < 0.001), SREs (2.0 versus 3.4 events/100 person-years, p < 0.001), and ADT utilization overall (7.4 versus 33.8 doses/100-person-years, p < 0.001) and > 3 years after treatment (3.6 versus 4.6 doses/100-person-years, p < 0.001). Overall and cancer specific costs were significantly lower for RP versus RT.

    CONCLUSIONS:
    RT for locally-advanced prostate cancer has a higher incidence of mortality, secondary diagnoses and interventions, SRE, and ADT utilization compared to RP. This may lead to increased costs and have implications for quality of life. Our findings support the utility of RP in appropriately selected men with locally-advanced prostate cancer given the possible decreased morbidity and survival benefit.

  2. #32
    [#28]
    Updates in advanced prostate cancer 2018 [
    2018, Editorial, Full Text]

    https://www.nature.com/articles/s41391-018-0100-7

    In 2017–18, several notable advances were made in the care of men with advanced or metastatic prostate cancer, and Prostate Cancer and Prostatic Diseases provided important insights and perspectives around each of these major advances. As one among the top global prostate-specific journals, we are seeing a major increase in our impact factor and global reach, paralelling the increase in the basic understanding of the biology and treatment of prostate cancer. In this editorial, I have selected nine key manucripts from the past year in our journal that highlight and provide novel insights into these important clinical and translational advances. These are provided below with their citations, links, and a brief description of the article’s importance, with the intent of bringing attention to these works to the prostate cancer research community. These are in no particular order, as each has been heavily cited and read, and emphasizes the unique aspects of advanced prostate cancer clinical practice and research.
    (see Full Text)

  3. #33
    [#29]
    Survival and secondary interventions following treatment for locally-advanced prostate cancer
    [2018]

    https://europepmc.org/abstract/med/30281010

    Abstract
    INTRODUCTION:The utility of radical prostatectomy (RP) for locally-advanced prostate cancer remains unknown. Retrospective data has shown equivalent oncologic outcomes compared to radiation therapy (RT). RP may provide local tumor control and prevent secondary interventions from local invasion, and may decrease costs. MATERIALS AND METHODS:Using SEER-Medicare data from 1995-2011 we identified men with locally-advanced prostate cancer undergoing RP or RT. Rates of post-treatment diagnoses and interventions were identified using ICD-9 and CPT codes. Skeletal related events (SRE), androgen deprivation therapy (ADT) utilization, all-cause mortality, prostate cancer-specific mortality, and costs were compared. RESULTS:A total of 8367 men with locally-advanced prostate cancer were identified (6200 RP, 2167 RT). RT was associated with increased urinary obstruction, hematuria, infection, and cystoscopic intervention while RP was associated with increased urethral stricture intervention and erectile dysfunction. Compared to RT, RP was associated with decreased all-cause mortality (3.1 versus 5.2 deaths/100-person-years, p < 0.001), prostate cancer-specific mortality (0.8 versus 2.0 deaths/100-person-years, p < 0.001), SREs (2.0 versus 3.4 events/100 person-years, p < 0.001), and ADT utilization overall (7.4 versus 33.8 doses/100-person-years, p < 0.001) and > 3 years after treatment (3.6 versus 4.6 doses/100-person-years, p < 0.001). Overall and cancer specific costs were significantly lower for RP versus RT. CONCLUSIONS:RT for locally-advanced prostate cancer has a higher incidence of mortality, secondary diagnoses and interventions, SRE, and ADT utilization compared to RP. This may lead to increased costs and have implications for quality of life. Our findings support the utility of RP in appropriately selected

  4. #34
    [#30]
    Recent trends in the management of advanced prostate cancer
    [2018]

    Abstract

    Advanced prostate cancer includes a wide spectrum of disease ranging from hormone naïve or hormone sensitive to castration resistant, both containing populations of men who have demonstrable metastatic and non-metastatic states. The mainstay of treatment for metastatic hormone-sensitive prostate cancer is androgen deprivation therapy (ADT). However, recent level 1 evidence demonstrates that the addition of chemotherapy or abiraterone acetate to ADT results in significant survival advantage as compared with ADT alone. Furthermore, in non-metastatic castration-resistant prostate cancer (M0 CRPC), two second-generation anti-androgens, apalutamide and enzalutamide, when used in combination with ADT, have demonstrated a significant benefit in metastasis-free survival. Here, we review the most recent studies leading to these significant changes in the treatment of advanced prostate cancer.
    69 yr at Dx, BPH x 20 yr, 9 (!) neg. Bx, PCA3 -
    2013 TURP (90→30 g) path neg. then 6-mo. checks
    6-06-17 Nodule on R + PSA rise on finasteride: 3.6→4.3
    6-28-17 Bx #10: 2/14 cores: G10 (5+5) 50% RB, G9 (4+5) 3% RLM
    Bone scan, CTs, X-rays: neg.
    8-7-17 Open RP, neg. frozen sections, Duke Regional
    SM EPE BNI LVI SVI LNI(16): negative, PNI+, nerves spared
    pT2c pN0 pMX acinar adenocarcinoma G9 (4+5) 5% of prostate (4.5x5x4 cm, 64 g)
    11-10-17 Decipher 0.37 Low Risk: 5-yr met risk 2.4%, 10-yr PCa-specific mortality 3.3%
    Dry; ED OK with sildenafil
    9-16-17 (5 wk) PSA <0.1
    LabCorp uPSA, Roche ECLIA:
    11-28-17 (3 m ) 0.010
    02-26-18 (6 m ) 0.009
    05-30-18 (9 m ) 0.007
    08-27-18 (1 yr.) 0.018 (?)
    09-26-18 (13 m) 0.013 (30-day check)
    11-26-18 (15 m) 0.012
    02-25-19 (18 m) 0.015
    05-22-19 (21 m) 0.015

  5. #35
    [#31]
    Management of Prostate Cancer Patients with Clinically Positive Lymph Nodes
    [2019, Full Text]

    https://euoncology.europeanurology.c...059-8/fulltext

    Abstract

    Patients with prostate cancer (PC) with clinically positive lymph nodes detectable via conventional imaging have always been perceived as a challenge, especially with regard to the value of applying local treatment. Over the years, many of these patients have been treated with androgen deprivation therapy (ADT) only. Studies in this specific setting are scarce and mostly retrospective. This issue of European Urology Oncology contains a systematic review of the role of local treatments in this patient population by Ventimiglia et al.

  6. #36
    [#32]
    Adjuvant Chemotherapy for High-Risk Localized Prostate Cancer: Time for Change or Need More Time to Change?
    [2019, Letter to the editor]

    https://ascopubs.org/doi/10.1200/JCO.19.00977

    TO THE EDITOR:

    Rosenthal et al1 published the long-awaited results of Radiation Therapy Oncology Group (RTOG) study 0521, the first prospective trial, to my knowledge, to show objectively that adjuvant docetaxel chemotherapy for six cycles after primary definitive radiation and androgen-deprivation therapy (ADT) improves all known clinical parameters of disease-free survival, disease-specific survival, and—most important—overall survival. Embracing the benefit of early docetaxel, given its now-fundamental role in prostate cancer, is not difficult. Results from CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) have paved the way to the establishment of earlier chemotherapy treatment as better in metastatic hormone-sensitive prostate cancer, especially in those with high-volume disease. Even before the peer-reviewed publication of RTOG 0521, and in part as a result of published early results from GETUG 12 (Groupe d’Étude des Tumeurs Urogénitales) that showed improvement in relapse-free survival with docetaxel and estramustine (though 12-year follow-up showed no difference in overall or prostate cancer–specific survival),2,3 adoption of adjuvant chemotherapy in the National Comprehensive Cancer Network guidelines in the 2016 version led to the consideration of adjuvant docetaxel for fit men with high- and very-high–risk localized prostate cancer.4 However, important gaps in the analyses about adjuvant chemotherapy are worth addressing. Given that RTOG 0521 is the only adjuvant docetaxel trial with positive results, as far as overall survival is concerned, the question remains whether the statistical significance that is seen in this study is a result of true clinical benefit or is a statistical aberration wrought by the default one-sided hypothesis that was, understandably, chosen at the time and on the basis of the RTOG 99-02 trial.5 This one-sided hypothesis allowed an earlier read-out of the results on the basis of a smaller number of patients accrued. RTOG 0521 was designed to detect a 7% improvement in 4-year overall survival from 86% to 93% (hazard ratio [HR], 0.49; one-sided α, .05; 90% power). Although the study showed statistically significant results at a P value of .034—which the study mandated as positive if the one-sided P value from a log-rank test in a modified intent-to-treat population was < .04—the HR remained high (far higher than the prestated HR of 0.49) for the planned analyses during a short median follow-up time of 5.7 years. Perhaps this is due in part to much better outcomes overall and fewer deaths in RTOG 0521, given the improvement in the dose escalation scheme for all of the standard radiation arms (ie, radiation doses to the prostate in RTOG 99-02 were 70 Gy v 72 to 75 Gy in RTOG 0521). However, the radiation doses in both trials were still lower than most contemporary doses of radiation, which involve 78 Gy or more; radiation doses may be able to compensate for outcome differences.

    Another approach to distinguish patients who will clinically benefit would be to examine the subgroup analyses of patients in RTOG 0521. Furthermore, analyses of information about treatment beyond progression may help elucidate any impact of life-prolonging therapy for those who develop distant metastases. Although benefit from docetaxel is seen in the patients with M1 castration-sensitive disease, patients with low-volume disease do not derive the same benefit.6 The lack of overwhelming benefit in the M0 space was highlighted in a meta-analyses that included RTOG 0521 and the M0 arms of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) and GETUG 12 trials, in which an HR of 0.87 (95% CI, 0.69 to 1.09; P = .218 ) translated to a potential absolute improvement of 2% (95% CI, −2% to 7%), though wide variability in the CI was seen.7 Although this analysis included a heterogeneous population of patients, the beneficial effects of chemotherapy are predicated on the notion that a large proportion of men with high-risk localized disease may harbor micrometastatic or androgen-insensitive disease.

    Which of the factors play the most important role to establish the benefit of adjuvant chemotherapy? Perhaps it is the type of primary local therapy (it would seem that most radical prostatectomy trials to assess adjuvant chemotherapy were found wanting; eg, the Scandinavian Prostate Cancer Group [SPCG] 12 trial8 ), prednisone use (or lack thereof, as in the SPCG 13 trial9), concurrent ADT (or lack thereof, as in SPCG 12), duration of ADT (longer at 24 months in RTOG 0521 v shorter at 1 year in SPCG 13), type of chemotherapy (RTOG 99-02 used a nondocetaxel regimen), or number of docetaxel cycles (GETUG 12 used only four cycles coupled with estramustine2)? More refinement or use of molecular or genomic classifiers to predict which patient is most likely to benefit from adjuvant chemotherapy is of paramount importance, given the need to define those who are destined for curative intent treatment—which, after all, is the goal of any adjuvant therapy. Nonetheless, data from RTOG 0521 set the tone and will form the baseline upon which future adjuvant trials can improve.
    Last edited by DjinTonic; 07-08-2019 at 07:42 PM.

  7. #37
    [#33]
    Management of cT4 Prostate Cancer
    [2019, Review]

    https://www.ncbi.nlm.nih.gov/pubmed/31266732

    Abstract

    While radiotherapy with androgen deprivation therapy is the current standard of care for the treatment of stage cT4 prostate cancer (PC), surgery may also be an appropriate option in selected patients as part of a multimodal approach. The role and the sequence with which to optimize therapy combinations in this setting are still unknown. This mini review summarizes the current evidence for management of cT4 PC. PATIENT SUMMARY: This mini review examines current evidence for the treatment options for locally advanced prostate cancer. The role of surgery in these patients can be considered as part of a combination treatment strategy along with other modalities such as radiotherapy and hormone therapy.

 

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