Long-term Prostate Cancer Outcomes Research Articles

Determining Long-term Prostate Cancer Outcomes for Active Surveillance Patients Without Early Disease Progression: Implications for Slowing or Stopping Surveillance

Background and objectiveActive surveillance (AS) of prostate cancer (PCa) is the standard of care for low-grade disease, but there is limited guidance on tailoring protocols for stable patients. We investigated long-term outcomes for patients without initial progression and risk factors for upgrade. MethodsMen on AS with Gleason grade group (GG) 1 PCa on three serial biopsies, ≥5 yr without progression, and ≥10 yr of follow-up were included. Outcomes were upgrade (GG ≥2), major upgrade (GG ≥3), progression to treatment, metastasis, PCa-specific survival, and overall survival. Cox proportional hazards regression models were used to estimate the associations between patient characteristics and risk of upgrade. Key findings and limitationsA total of 774 men met the inclusion criteria. At 10, 12, and 15 yr, upgrade-free survival rates were 56%, 45%, and 21%; major upgrade–free survival rates were 88%, 83%, and 61%; treatment-free survival rates were 86%, 83%, and 73%; metastasis-free survival rates were 99%, 99%, and 98%; and overall survival rates were 98%, 96%, and 95%, respectively. PCa-specific survival was 100% at 15 yr. On a multivariable analysis, year of diagnosis, age, body mass index (BMI), and biopsy core positivity were associated with upgrade (all p < 0.01), whereas age and prostate-specific antigen (PSA) density were associated with major upgrade. Conclusions and clinical implicationsPatients without progression for 5 yr on AS had modest rates of upgrade and low rates of metastasis, and mortality at 15 yr of follow-up. Year of diagnosis, older age, increased BMI, and increased biopsy core positivity were associated with upgrade, whereas older age and greater PSA density were associated with an increased risk of major upgrade. A subset of these patients may benefit from deintensification of AS protocols. Patient summaryThere are little reported data or clinical guidelines for patients with prostate cancer (PCa) who are stable for many years on active surveillance (AS). We show, in a large cohort, that PCa patients without progression for 5 yr on AS have modest rates of upgrade and very low rates of metastasis, and mortality rates at 15 yr of follow-up, and that older age, increased body mass index, and increased PCa volume are associated with an increased likelihood of future upgrade. This study supports continued AS in this patient population and deintensification in select patients.

MP67-01 THE IMPACT OF LYMPHOVASCULAR INVASION ON LONG-TERM CANCER OUTCOMES FOLLOWING RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP67-01 THE IMPACT OF LYMPHOVASCULAR INVASION ON LONG-TERM CANCER OUTCOMES FOLLOWING RADICAL PROSTATECTOMY Niranjan Sathianathen, Marc Furrer, Clancy Mulholland, Nathan Lawrentschuk, and Niall Corcora Niranjan SathianathenNiranjan Sathianathen More articles by this author , Marc FurrerMarc Furrer More articles by this author , Clancy MulhollandClancy Mulholland More articles by this author , Nathan LawrentschukNathan Lawrentschuk More articles by this author , and Niall CorcoraNiall Corcora More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003330.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymphovascular invasion (LVI) has been shown to be associated with higher grade and stage of prostate cancer. However, the literature is scarce on its ability to predict long-term oncological outcomes. Therefore, we aim to evaluate the impact of LVI on long-term prostate cancer outcomes following radical prostatectomy. METHODS: A consecutive sample of patients with localised prostate cancer undergoing radical prostatectomy in a multicentre database was included in the analysis. Postoperative PSA measurements and clinical examinations were taken at 3, 6 and 12 months and afterwards yearly. Further diagnostic imaging was obtained with a rising PSA or clinical suspicion. Recurrence-free survival (RFS) and metastases-free survival (MFS) were analysed as a time-to-event outcome using Kaplan-Meier analyses with log-rank tests. To assess the effect of LVI, we created multivariable Cox proportional hazards models adjusting for relevant clinical and demographic characteristics. Ethics committee approval was obtained. RESULTS: A total of 3,732 men were included for analysis with a median follow-up of 44 months. LVI was detected in 18% (n=682). LVI was more common with increasing ISUP grade [RR 4.2, 95%CI 3.8-4.6] and pathological stage [RR 6.5, 95%CI 5.9-7.2]. The incidence of metastasis at 5-years was 12%. Men that were LVI+were more likely to develop metastatic disease than those that were LVI- (39% vs 6%, p<0.01). LVI was an independent predictor of metastasis [HR 2.2, 95%CI 1.7-3.0] and biochemical recurrence [HR 2.1, 95%CI 1.8-2.5]. This finding was consistently noted on subgroup analysis of men with both intermediate- and high-risk prostate cancer. CONCLUSIONS: Lymphovascular invasion is a prognostic indicator of adverse recurrence- and metastasis-free survival following surgery for prostate cancer. This can assist with risk-stratification following radical treatment and possibly aid decision-making regarding adjuvant treatment. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e943 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Niranjan Sathianathen More articles by this author Marc Furrer More articles by this author Clancy Mulholland More articles by this author Nathan Lawrentschuk More articles by this author Niall Corcora More articles by this author Expand All Advertisement PDF downloadLoading ...

The impact of pelvic lymph node dissection at the time of radical prostatectomy on long-term prostate cancer outcomes

The impact of pelvic lymph node dissection at the time of radical prostatectomy on long-term prostate cancer outcomes

Race-specific prostate cancer outcomes in a cohort of military health care beneficiaries undergoing surgery: 1990-2017.

There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-reported AA and CA men, and examines clinicopathologic features across self-reported CA, AA, Asian, and Hispanic men. This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi-center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan-Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR=1.25, 95% CI=1.06-1.48, p=0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR=0.73, 95% CI=0.39-1.33, p=0.302) and time from metastasis to overall death (HR=0.67, 95% CI=0.36-1.26, p=0.213). In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.

Adverse pathology as a predictor of distant metastasis and prostate cancer mortality with 20-year follow up.

219 Background: Adverse pathology (AP) at radical prostatectomy (RP) is often used as a proxy for long-term prostate cancer outcomes. The goal of this study was to assess the association of AP at RP, defined as high-grade (&gt; Grade Group 3) and/or non-organ confined disease (pT3), with distant metastasis and prostate cancer death. Methods: A stratified cohort sample of 428 patients was used to evaluate the association of adverse pathology with the risk of distant metastases and prostate cancer-specific mortality over 20 years after prostatectomy in 2641 patients treated between 1987-2004. Cox regression of cause-specific hazards was used to estimate the absolute risk of both endpoints, with death from other causes treated as a competing risk. Subgroup analysis in patients with low/intermediate risk disease potentially eligible for active surveillance was performed. Results: Among the 428 patients, 343 had AUA Low or Intermediate risk disease and 85 had High risk disease. Median follow-up time was 15.5 years (IQR 14.6–16.6 years). Using the cohort sampling weights for estimation, at RP 29.8% of patients had high-grade disease, 42.3 % had non-organ confined disease, 19.3% had both, and thus 52.8% had AP. Adverse pathology was highly associated with metastasis and prostate cancer mortality in the overall cohort (HR 12.30, 95% CI 5.30-28.55, and 10.03, 95% CI 3.42-29.47, respectively, both p&lt;0.001), and in the low/intermediate risk subgroup potentially eligible for active surveillance (HR 10.48, 95% CI 4.18-26.28, and 8.60, 95% CI 2.40-30.84, respectively, both p≤0.001). Conclusions: Adverse pathology at radical prostatectomy is highly associated with future development of metastasis and prostate cancer mortality and may be used as a short-term predictor of outcomes. [Table: see text]

1119 - Adverse pathology at radical prostatectomy, GPS™ test, and clinical/pathology features as predictors of long-term prostate cancer outcomes

1119 - Adverse pathology at radical prostatectomy, GPS™ test, and clinical/pathology features as predictors of long-term prostate cancer outcomes

Obesity, race, and long-term prostate cancer outcomes.

The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race. Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25kg/m2 ), overweight (25-29.9kg/m2 ), and obese (≥30kg/m2 ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders. Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30kg/m2 , seminal vesicle invasion, and positive surgical margins (all P≤.032). During a median follow-up of 7.4years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P=.035]). No interaction was found between BMI and race in predicting PCSM (P≥.88), BCR (P≥.81), CRPC (P≥.88), or metastasis (P≥.60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P≥.18). Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race.

Poorly controlled diabetes increases the risk of metastases and castration-resistant prostate cancer in men undergoing radical prostatectomy: Results from the SEARCH database.

Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP). The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only. A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P<.001) and more likely to be black (P=.013). The median follow-up after RP was 6.8years (interquartile range, 3.7-10.6years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P=.031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P=.023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P=.067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P=.058]). Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes.

Obese patients with castration-resistant prostate cancer may be at a lower risk of all-cause mortality: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

To assess whether obesity is associated with progression to metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM), in patients with non-metastatic castration-resistant prostate cancer (non-mCRPC). At the population level, obesity is associated with prostate cancer mortality; however, some studies have found that higher body mass index (BMI) is associated with better long-term prostate cancer outcomes amongst men with mCRPC. We identified 1 192 patients with non-mCRPC from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BMI was calculated from height and weight abstracted from the medical records at the time closest to but prior to CRPC diagnosis and categorised as underweight (<21 kg/m2 ), normal weight (21-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). Competing risks regression and Cox models were used to test associations between obesity and progression to metastasis, PCSM, and ACM, accounting for confounders. Overall, 51 (4%) men were underweight, 239 (25%) were normal weight, 464 (39%) were overweight, and 438 (37%) were obese. In adjusted analysis, higher BMI was significantly associated with reduced ACM (hazard ratio [HR] 0.98, P = 0.012) but not PCSM (HR 1.00, P = 0.737) or metastases (HR 0.99, P = 0.225). Likewise, when BMI was treated as a categorical variable in adjusted models, obesity was not associated with PCSM (HR 1.11, P = 0.436) or metastases (HR 1.06, P = 0.647), but was associated with decreased ACM (HR 0.79, P = 0.016) compared to normal weight. No data were available on treatments received after CRPC diagnosis. Amongst patients with non-mCRPC obesity was associated with better overall survival. Although this result mirrors evidence from men with mCRPC, obesity was not associated with prostate cancer outcomes. Larger studies are needed to confirm these findings.

High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer

Objective: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa.Materials and methods: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category.Results: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45–9.97).Conclusion: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.

Abstract B26: iNOS expression and lethal prostate cancer in patients with localized disease

Abstract Inducible nitric oxide synthase (iNOS) has demonstrated both tumor-promoting and tumor-inhibiting effects in prostate cancer. However, the relationship between iNOS protein expression and long-term prostate cancer outcomes is unclear. We evaluated iNOS expression in tumor epithelia and stroma in 300 men with localized tumors diagnosed incidentally by transurethral resection of the prostate (TURP) in Sweden. In this extreme case-control design, cases (N=132) died of prostate cancer and controls (N=168) survived at least 8 years following diagnosis without death from prostate cancer or a competing cause. Immunohistochemistry was undertaken with a polyclonal rabbit anti-human NOS2 antibody (Abcam) and the Ventana (Roche) semi-automated staining system. Two observers individually scored the staining according to intensity and number of positive cells from 0-3. The median value across cores in each patient were then categorized as &amp;lt;1, &amp;gt;1-&amp;lt;2, and &amp;gt;2, separately for epithelial and stromal compartments. Odds ratios for lethal prostate cancer were estimated with logistic regression controlling for the matching factors (age, calendar year of diagnosis), as well as tumor stage, Gleason score, and percent tumor. iNOS was expressed by stromal-associated M1 macrophages and fibroblasts, as well as tumor cells. Gleason score was positively associated with both stromal and epithelial iNOS staining. In the stroma, there was no statistically significant association between iNOS expression and lethal prostate cancer after adjustment for clinical covariates. However, the odds of lethal prostate cancer increased with tumor expression of iNOS in the fully adjusted model. Compared to patients with the lowest category of iNOS expression, the odds ratios for lethal prostate cancer were 2.96 (95% CI: 1.26-6.96) for patients in the second category and 3.80 (95% CI: 1.45-9.97) for patients in the top category. These results suggest that iNOS may help to identify patients with aggressive prostate cancer at the time of diagnosis, or may be a therapeutic target. Given previously reported in vitro data suggesting that iNOS promotes proliferation of androgen-independent prostate tumors, future analyses will investigate association between iNOS expression and time to castration-resistant prostate cancer in this patient population. Citation Format: Jennifer R. Rider, Ann Erlandsson, Chirag Vyas, Sabina Davidsson, Jessica Carlsson, Swen-Olof Andersson, Ove Andren. iNOS expression and lethal prostate cancer in patients with localized disease [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B26.

Abstract 880: Obesity predicts prostate cancer-specific mortality after radical prostatectomy: Results from the SEARCH database

Abstract INTRODUCTION: At the population level among otherwise “healthy” men, obesity is associated with prostate cancer mortality. However, few studies analyzed the associations between obesity and long-term progression after surgery, such as castration-resistant prostate cancer (CRPC) and prostate cancer-specific mortality (PCSM). We examined the effect of obesity at the time of radical prostatectomy (RP) on long-term prostate cancer-specific outcomes among men treated at Veterans Affairs Hospitals in the USA. METHODS: We combined data from patients undergoing RP at six Veterans Affairs Medical Centers (West Los Angeles, San Diego, and Palo Alto, CA; Augusta, GA; and Durham and Asheville, NC) into the SEARCH database. Our exposure, body mass index (BMI) was abstracted from the medical records at the time of but prior to RP and categorized as normal weight (&amp;lt;25 kg/m2), overweight (25-29.9kg/m2), and obese (≥30kg/m2). Crude and adjusted Cox models accounting for known risk cofactors were used to examine the associations between BMI and PCSM (primary outcome), biochemical recurrence (BCR) and CRPC. Hazard ratios for the risk of CRPC and PCSM were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk. RESULTS: Overall, 839 (23%) men had normal weight, 1,675 (45%) were overweight, and 1,184 (32%) were obese. A higher BMI was associated with younger age at surgery (p&amp;lt;0.001), lower PSA (median 6.9 vs. 6.3 vs. 6.1; p&amp;lt;0.001), and a shorter follow-up (p = 0.009). After adjusting for clinical and pathological features, both overweight (HR 2.85, p = 0.039) and obesity (HR 3.38, p = 0.017) were significantly associated with PCSM relative to normal weight. Obesity (vs. normal weight) was also associated with a higher risk of BCR (HR = 1.20, p = 0.026) and CRPC (HR = 2.12, p = 0.026), even after adjusting for clinical and pathological characteristics. Overweight was not associated with BCR (HR = 1.01, p = 0.948) or CRPC (HR = 1.44, p = 0.274) on multivariable analysis. CONCLUSIONS: Our study supports the hypothesis that obese men undergoing RP are at increased risk of worse long-term prostate cancer outcomes including PCSM. Our findings are consistent with a growing body of literature documenting that obesity in general is associated with more aggressive prostate cancer. Citation Format: Adriana C. Vidal, Lauren E. Howard, Matthew R Cooperberg, Christopher J. Kane, William J. Aronson, Martha K. Terris, Christopher L. Amling, Stephen J Freedland. Obesity predicts prostate cancer-specific mortality after radical prostatectomy: Results from the SEARCH database. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 880. doi:10.1158/1538-7445.AM2015-880

Prostate Cancer Ki-67 (MIB-1) Expression, Perineural Invasion, and Gleason Score as Biopsy-Based Predictors of Prostate Cancer Mortality: The Mayo Model

To determine the role of cellular proliferation and other biopsy-based features in the prediction of prostate cancer mortality. Between 1993 and 2012, our institution has performed quantitation of prostate cancer DNA ploidy and Ki-67 (MIB-1) on most prostate cancer needle biopsy specimens. The outcomes of 451 consecutive patients with biopsy-proven cancer treated by radical prostatectomy between January 24, 1995, and December 29, 1998, without neoadjuvant hormonal therapy were assessed. Clinical and biopsy information obtained before radical prostatectomy was placed in multivariate Cox proportional hazards regression models to predict local or systemic progression and cancer-specific death. Predictive ability was evaluated using a concordance index. With a median follow-up of 12.9 years, 46 patients experienced local or systemic progression, and 18 patients died of prostate cancer. On multivariate analysis, the biopsy features of Ki-67 expression, perineural invasion, and Gleason score were associated with local or systemic progression. Ki-67 expression, perineural invasion, and Gleason score were associated with cancer-specific death with a concordance index of 0.892. After adjusting for perineural invasion and Gleason score, each 1% increase in Ki-67 expression was associated with a 12% increased risk of cancer-specific death (P<.001). Ki-67 expression alone was a strong predictor of cancer-specific outcomes and improved the predictive ability of currently used algorithms. This study documents that long-term prostate cancer outcomes are best estimated with a combination of Gleason score, perineural invasion, and Ki-67 expression. Given its low cost, rapid assessment, and strong predictive power, we believe that adding Ki-67 expression to perineural invasion and Gleason score at biopsy should be considered a standard by which all new biomarkers are compared before introducing them into clinical practice.