Among men with prostate cancer who were randomly assigned to radical prostatectomy or observation and followed for a median of 12.7 years, overall survival was not significantly increased by surgery.
Over 700 men were assigned to radical prostatectomy or observation after receiving a diagnosis of prostate cancer, usually on the basis of elevated PSA levels. After a median of 10 years, ...between-group differences in all-cause and prostate-cancer mortality were not significant.
The treatment of early-stage prostate cancer remains controversial, especially for tumors detected by means of prostate-specific antigen (PSA) testing.
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Systematic reviews have provided inadequate information for assessing the comparative effectiveness of treatments and any associated harms.
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Although the lifetime risk of receiving a diagnosis of prostate cancer is about 17%, the risk of dying from the disease is approximately 3%, suggesting that conservative management may be appropriate for many men.
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Two randomized trials compared radical prostatectomy with observation but were conducted before PSA testing became widespread.
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One study failed to show a significant difference in overall mortality after . . .
Black men are more likely to die of prostate cancer than white men. In men with similar stages of disease, the contribution of biological vs nonbiological differences to this observed disparity is ...unclear.
To quantify the association of black race with long-term survival outcomes after controlling for known prognostic variables and access to care among men with prostate cancer.
This multiple-cohort study included updated individual patient-level data of men with clinical T1-4N0-1M0 prostate cancer from the following 3 cohorts: Surveillance, Epidemiology, and End Results (SEER n = 296 273); 5 equal-access regional medical centers within the Veterans Affairs health system (VA n = 3972); and 4 pooled National Cancer Institute-sponsored Radiation Therapy Oncology Group phase 3 randomized clinical trials (RCTs n = 5854). Data were collected in the 3 cohorts from January 1, 1992, through December 31, 2013, and analyzed from April 27, 2017, through April 13, 2019.
In the VA and RCT cohorts, all patients received surgery and radiotherapy, respectively, with curative intent. In SEER, radical treatment, hormone therapy, or conservative management were received.
Prostate cancer-specific mortality (PCSM). Secondary measures included other-cause mortality (OCM). To adjust for demographic-, cancer-, and treatment-related baseline differences, inverse probability weighting (IPW) was performed.
Among the 306 100 participants included in the analysis (mean SD age, 64.9 8.9 years), black men constituted 52 840 patients (17.8%) in the SEER cohort, 1513 (38.1%) in the VA cohort, and 1129 (19.3%) in the RCT cohort. Black race was associated with an increased age-adjusted PCSM hazard (subdistribution hazard ratio sHR, 1.30; 95% CI, 1.23-1.37; P < .001) within the SEER cohort. After IPW adjustment, black race was associated with a 0.5% (95% CI, 0.2%-0.9%) increase in PCSM at 10 years after diagnosis (sHR, 1.09; 95% CI, 1.04-1.15; P < .001), with no significant difference for high-risk men (sHR, 1.04; 95% CI, 0.97-1.12; P = .29). No significant differences in PCSM were found in the VA IPW cohort (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and black men had a significantly lower hazard in the RCT IPW cohort (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). Black men had a significantly increased hazard of OCM in the SEER (sHR, 1.30; 95% CI, 1.27-1.34; P < .001) and RCT (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) IPW cohorts.
In this study, after adjustment for nonbiological differences, notably access to care and standardized treatment, black race did not appear to be associated with inferior stage-for-stage PCSM. A large disparity remained in OCM for black men with nonmetastatic prostate cancer.
Very long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain.
To determine long-term effects of surgery versus observation on all-cause mortality ...for men with early prostate cancer.
This study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n=731) ≤75yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50ng/ml, life expectancy ≥10yr, and medically fit for surgery.
Radical prostatectomy versus observation.
All-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods.
During 22.1yr (median follow-up for survivors=18.6yr; interquartile range: 16.6–20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 95% confidence interval {CI}: 0.70–1.00; p= 0.044 absolute risk reduction = 5.7 percentage points, 95% CI: –0.89 to 12%; relative risk: 0.92 95% CI: 0.84–1.01). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9–14.3) versus 12.6 yr (95% CI: 11.8–13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality.
Surgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease.
In this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment.
Surgery may be associated with small reductions in all-cause mortality compared with observation in men with early prostate cancer. Strategies are needed to communicate these findings, enhance identification of individuals benefitting from early intervention, and reduce ineffective and/or overtreatment harms.
IMPORTANCE: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. OBJECTIVE: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive ...treatment. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. EXPOSURES: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was prostate cancer–specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. RESULTS: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer–specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer–specific mortality than either RP or EBRT (cause-specific HRs of 0.38 95% CI, 0.21-0.68 and 0.41 95% CI, 0.24-0.71). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 95% CI, 0.17-0.43 for RP and 0.30 95% CI, 0.19-0.47 for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 95% CI, 0.46-0.96 for RP and 0.61 95% CI, 0.45-0.84 for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer–specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 95% CI, 0.67-1.26, 0.90 95% CI, 0.70-1.14, 1.07 95% CI, 0.80-1.44, and 1.34 95% CI, 0.85-2.11). CONCLUSIONS AND RELEVANCE: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer–specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.
We tested the hypothesis that the poor recovery of the coral populations on reefs in the Florida Keys is related to low coral recruitment. In the summer of 2011, we deployed 240 terracotta tiles at ...eight study sites in a balanced design: (i) among three depths; and (ii) between fished and unfished reefs. Corals recruited to ∼ 40% of the deployed tiles, with more corals settling on tiles on unfished reefs than on fished reefs. The apparent effect of protection was not a consequence of different densities of herbivorous fishes, but was more likely related to local hydrography and the tendency of the no-take reserves to act as larval sinks, particularly in the lower Florida Keys. There was a mismatch between the coral taxa that recruited and the adult coral assemblages, suggesting that recruits were arriving but not surviving to contribute to coral recovery.
Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of ...comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year.
Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group.
None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle.
Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.
Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was ...associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP).
We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database.
In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P < or = .004), and biochemical progression (comparing prostate weight < 20 v > or = 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound-measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P < or = .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06).
Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.
M2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and ...progression of CRPC and inhibit tumor-associated M2-like macrophages.
MycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm
. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.
The ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm
) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).
Dietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC.
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