To find reliable biomarkers for high‐grade malignancy, the relationship between immunohistochemical L‐type amino‐acid transporter 1 (LAT1) expression of biopsy samples, determined with the newly ...developed monoclonal antibody against human LAT1, and prognosis of patients with prostate cancer, was investigated. The intensity and score of immunohistochemical LAT1 expression of first biopsy samples were assessed using the modified Sinicrope et al. method and were found to be correlated with poor survival for the study group of 114 surgically treated patients as a whole (P = 0.0002 and 0.0270, respectively). LAT1 intensity further had a significant relationship (P = 0.0057) with prognosis in pathological T3 + T4 groups. Multivariate analysis indicated that the LAT1 intensity and score were more reliable prognostic markers, compared with the Gleason score and the Ki‐67 labeling index. A relationship of the LAT1 intensity and score with prognosis could also be confirmed in 63 patients with inoperable cancer (P = 0.0070 and <0.0001, respectively). Similarly, significant differences in prognosis were confirmed in clinical T3 + T4 groups (P = 0.0091 and 0.0244, respectively). Moreover, the combination of LAT1 expression and Gleason score was found to have a more reliable correlation with prognosis. Thus, elevated LAT1 expression in prostate cancers is a novel independent biomarker of high‐grade malignancy, which can be utilized together with the Gleason score, which is mainly dependent on cellular and structural atypia, to assess prognosis.
Background
Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial showed the survival benefit for prostate radiotherapy in newly diagnosed prostate ...cancer patients with a low metastatic burden. The result raises the next question whether additional radiotherapy to metastatic sites could improve the survival in those with a low metastatic burden.
Methods
We evaluated the efficacy and safety of prostate‐directed radiotherapy (PDRT) with or without metastasis‐directed radiotherapy (MDRT) in newly diagnosed oligometastatic patients who underwent combination of high‐dose‐rate prostate brachytherapy, external beam radiotherapy, and androgen deprivation therapy. Forty patients with bone metastasis and node positive prostate cancer were retrospectively analyzed. Of these, 22 (55%), 3 (7%), and 15 (38%) patients had N1M0, M1a, and M1b, respectively. Eighteen patients (45%) received MDRT to all metastatic sites. All patients initially underwent ≧6 months of androgen deprivation therapy. Oligometastatic disease was defined as presence of five or fewer metastatic lesions. Median follow‐up period was 62.5 months.
Results
Of the 40 patients, the 5‐year castration‐resistant prostate cancer (CRPC)‐free survival rate and cancer‐specific survival was 64.4% and 87.9%, respectively. Pre‐ or post‐treatment predictive value including prostate‐specific antigen (PSA) at diagnosis ≥20 ng/mL, Gleason grade group 5, positive biopsy core rate ≥51%, PSA nadir level of ≥0.02 ng/mL after the radiotherapy, and no MDRT were significantly associated with progression to CRPC. Patients with MDRT had significantly higher probability of achieving a PSA level of <0.02 ng/mL than those without the therapy (88.8% vs 54.5%, P = 0.0354) and consequently had a better CRPC‐free survival than those without the therapy (HR 0.319, 95%CI: 0.116‐0.877). Comparing PDRT alone, PDRT with MDRT did not significantly increase the incidences of genitourinary and gastrointestinal toxicities.
Conclusions
This single‐institutional study revealed the feasibility of combining prostate brachytherapy and MDRT for newly diagnosed oligometastatic prostate cancer. This combined approach has potential to prolong CRPC‐free survival.
Abstract
We compared clinical outcomes associated with seed brachytherapy (SEED-BT) alone and SEED-BT plus external-beam radiotherapy (EBRT) for intermediate-risk prostate cancer using propensity ...score-matched analysis. From 2006 to 2011, 993 patients diagnosed with intermediate-risk were treated with either SEED-BT alone (
n
= 775) or SEED-BT plus EBRT (
n
= 158) at 3 tertiary hospitals. In the propensity score-matched analysis (102 pairs), median follow-up was 95 months (range 18–153 months). The 8-year biochemical recurrence-free rate (bRFR) was significantly better with SEED-BT alone than with combined radiotherapy (93.3% vs. 88.4%; HR 0.396; 95% CI 0.158–0.991). Grade 2 or greater late genitourinary toxicities were significantly fewer with SEED-BT alone than with combined radiotherapy (21.0% vs. 33.2%; HR 0.521; 95% CI 0.308–0.881). Similarly, grade 2 or greater late gastrointestinal toxicities were significantly fewer with SEED-BT alone (0% vs. 12.2%; HR 0.125; 95% CI 0.040–0.390). For the unfavorable intermediate-risk subgroups, SEED-BT alone yielded a significantly better bRFR than the combined radiotherapy (HR 0.325; 95% CI 0.115–0.915). SEED-BT alone might be a better disease-management plan than SEED-BT plus EBRT for intermediate-risk prostate cancer regardless of favorable and unfavorable characteristics.
: Recent advances in high‐intensity focused ultrasound, which was developed in the 1940s as a viable thermal tissue ablation approach, have increased its popularity. High‐intensity focused ...ultrasound is currently utilized the most in Europe and Japan, but has not yet been approved by the Food and Drug Administration, USA, for this indication. The purpose of the present report is to review the scientific foundation of high‐intensity focused ultrasound technology and the clinical outcomes achieved with commercially available devices. Recently published articles were reviewed to evaluate the current status of high‐intensity focused ultrasound as a primary or salvage treatment option for localized prostate cancer. Improvements in the clinical outcome as a result of technical, imaging and technological advancements are described herein. A wide range of treatment options for organ‐confined prostate cancer is available. However, high‐intensity focused ultrasound is an attractive choice for men willing to choose less invasive options, although establishing the efficacy of high‐intensity focused ultrasound requires longer follow‐up periods. Technological advances, together with cultural and economic factors, have caused a dramatic shift from traditional open, radical prostatectomy to minimally invasive techniques. High‐intensity focused ultrasound is likely to play a significant role in the future of oncology practice.
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Accumulation of myeloid-derived suppressor cells (MDSCs) to tumors is related to cancer prognosis. We investigated the contribution of host stromal microsomal prostaglandin E ...synthase-1 (mPGES-1) to the accumulation of MDSCs in metastasized lungs of prostate cancer in mice.
Eight-week-old male C57Bl/6 wild type (WT) mice and mPGES-1 knock out mice (mPGES-1KO) were injected with RM9 murine prostate cancer cell line (5 × 106 cells/mL). Lung metastasis was evaluated by the number of colonies, the weight of the lung, and the number of MDSCs (CD11b+Gr1+ cells) in the lung.
Intravenous injections of RM9, a murine prostate cancer cell line to WT mice revealed that lung metastasis and accumulation of MDCSs were suppressed with treatments with a Gr1 antibody, a COX-2 inhibitor, and an mPGES-1 inhibitor. Lung metastasis and accumulation of CD11b+Gr1+MDSCs were suppressed in mPGES-1KO mice. The mRNA level of stromal cell-derived factor-1 (SDF-1) in the lung and the number of accumulated SDF-1-expressing CD11b+Gr1+ MDSCs were elevated at an early stage in lung metastasis of C-X-C chemokine receptor type 4 (CXCR4)-expressing RM9 in an mPGES-1-dependent manner. The number of CXCR4-expressing CD11b+Gr1+MDSCs in WT mice was higher than that in mPGES-1KO mice. RM9 lung metastasis and accumulation of CD11b+Gr1+MDSCs were suppressed by CXCR4 antibody in WT mice but not in mPGES-1KO. WT mice transplanted with mPGES-1 KO bone marrow (BM) showed a significant reduction in lung metastasis and accumulation of CD11b+Gr1+MDSCs.
These results suggest that mPGES-1 enhances tumor metastasis by inducing accumulation of BM-derived MDSCs. Selective mPGES-1 inhibitors might, therefore, represent valuable therapeutic tools for the suppression of tumor metastasis.
Background: High‐intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease‐free survival rates, predictors of ...clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU.
Methods: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate‐specific antigen (PSA) level were 70 years (range 44–88) and 9.76 ng/mL (range 3.39–89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow‐up period for all patients was 18.0 months (range 4–68).
Results: The biochemical disease‐free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease‐free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01–20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P < 0.0001). Multivariate analysis identified pretreatment PSA (P < 0.0001) as a independent predictor of relapse.
Conclusion: High‐intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.
To compare dosimetric parameters, seed migration rates, operation times, and acute toxicities of intraoperatively built custom-linked (IBCL) seeds with those of loose seeds for prostate ...brachytherapy.
Participants were 140 patients with low or intermediate prostate cancer prospectively allocated to an IBCL seed group (n=74) or a loose seed group (n=66), using quasirandomization (allocated by week of the month). All patients underwent prostate brachytherapy using an interactive plan technique. Computed tomography and plain radiography were performed the next day and 1 month after brachytherapy. The primary endpoint was detection of a 5% difference in dose to 90% of prostate volume on postimplant computed tomography 1 month after treatment. Seed migration was defined as a seed position >1 cm from the cluster of other seeds on radiography. A seed dropped into the seminal vesicle was also defined as a migrated seed.
Dosimetric parameters including the primary endpoint did not differ significantly between groups, but seed migration rate was significantly lower in the IBCL seed group (0%) than in the loose seed group (55%; P<.001). Mean operation time was slightly but significantly longer in the IBCL seed group (57 min) than in the loose seed group (50 min; P<.001). No significant differences in acute toxicities were seen between groups (median follow-up, 9 months).
This prospective quasirandomized control trial showed no dosimetric differences between IBCL seed and loose seed groups. However, a strong trend toward decreased postimplant seed migration was shown in the IBCL seed group.
We compared the oncological outcomes of patients who received seed brachytherapy (SEED-BT) with those who received radical prostatectomy (RP) for intermediate-risk prostate cancer.
Candidates were ...patients treated with either SEED-BT (n = 933) or RP (n = 334). One-to-one propensity score matching was performed to adjust the patients' backgrounds. We compared the biochemical recurrence (BCR)-free rate using the Phoenix definition (prostate-specific antigen PSA nadir plus 2 ng/mL) for SEED-BT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free rates using the same PSA cut-off value of 0.2 ng/mL for both SEED-BT and RP.
In the propensity score-matched analysis with 214 pairs, the median follow-up treatment was 96 months (range 1-158 months). Fifty-three patients (24.7%) were treated with combined SEED-BT and external-beam radiotherapy. Forty-three patients (20.0%) received salvage radiotherapy after RP. Comparing the BCR-free rate using the above definitions for SEED-BT and RP showed that SEED-BT yielded a significantly better 8-year BCR-free rate than did RP (87.4% vs. 74.3%, hazard ratio HR 0.420, 95% confidence interval CI 0.273-0.647). Comparing the 8-year BCR-free rate using the surgical definition for both treatments showed no significant difference between the two treatments (76.7% vs. 74.3%, HR 0.913, 95% CI 0.621-1.341). SEED-BT had a significantly better 8-year salvage hormonal therapy-free rate than did RP (92.0% vs. 85.6%, HR 0.528, 95% CI 0.296-0.942, P = 0.030). The 8-year metastasis-free survival rates (98.5% vs. 99.0%, HR 1.382, 95% CI 0.313-6.083, P = 0.668) and overall survival rates (91.9% vs. 94.6%, HR 1.353, 95% CI 0.690-2.650) did not significantly differ between the treatments.
The BCR-free rates did not significantly differ between patients treated with SEED-BT and those treated with RP for intermediate-risk prostate cancer even when they were directly compared using the surgical definition for BCR. SEED-BT and RP can be adequately compared for oncological outcomes.
Objective
The study objectives were to understand how patients view the quality of life in non‐metastatic castration‐resistant prostate cancer (nmCRPC), including unmet needs and what patients ...consider most important in treatment outcomes. A gap analysis was conducted on existing patient‐reported outcomes (PROs) measures versus what is missing from the patient perspective, to guide future development of PRO‐based real‐world evidence for nmCRPC in Japan. A conceptual model for nmCRPC Japanese patients’ HRQOL was also created.
Methods
This non‐interventional, qualitative study consisted of a targeted literature review, PRO instrument review, and interviews with 20 nmCRPC patients and five treating physicians. Triangulation of the gap analysis, evidence from the targeted review of the literature, and qualitative interview findings were employed to assess the comprehensiveness of current nmCRPC and HRQOL measures.
Results
Symptoms most reported by patients were frequent urination (70%), nocturia (65%), and general pain (65%). Others reported included lack of strength (30%). HRQOL impacts most reported were anxiety (45%) and worry (50%) about their diagnosis. Additional impacts mentioned were weight changes, loss of sleep, difficulty walking, loss of appetite, and difficulty traveling and seeking toilets in public.
The gap analysis revealed 31 symptoms and 33 impacts not covered in existing prostate cancer‐specific PRO instruments. Patients mentioned musculoskeletal symptoms such as fractures, leg pain, cramps, numbness, and loss of leg bone strength. Impacts not previously discussed in the literature or in outcome measures were feelings of self‐consciousness around diagnosis, stigma around illness, and the impact on mobility including traveling.
Conclusion
Key results reveal pain and urinary symptoms are the most experienced by Japanese nmCRPC patients. The diagnosis and treatment of disease leads to significant impacts in patient lives. Analysis revealed that symptoms and life impacts are missing in the current literature and outcome measures. Testing and debriefing of specific items could further substantiate these dimensions.
The study objectives were to understand how patients view quality of life in non‐metastatic castration resistant prostate cancer (nmCRPC), including, unmet needs, and what patients consider most impactful in treatment outcomes. Key results reveal pain and urinary symptoms are the most experienced by Japanese nmCRPC patients. The diagnosis and treatment of disease leads to significant impacts in patient lives. Analysis revealed that symptoms and life impacts are missing in the current literature and outcome measures. Testing and debriefing of specific items could further substantiate these dimensions.
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