Pretreatment Pretreatment Prostate-specific Antigen Research Articles

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Circulating tumor DNA and homologous recombination deficiency in bone-predominant mCRPC prior to radium-223 therapy.

203 Background: Radium-223 (Ra-223) is a bone-seeking alpha emitter that induces double-stranded DNA breaks, and the homologous recombination (HR) pathway is critical for repairing these breaks. While prior studies suggested that metastatic castrate-resistant prostate cancers (mCRPC) patients (pts) with HR-deficient (HRD+) tumors may be more likely to benefit from Ra-223, obtaining tissue for next generation sequencing to identify HRD+ is challenging in pts with bone-predominant disease. We hypothesized that circulating tumor DNA (ctDNA) would allow for broader identification of HRD+ to assess association with clinical outcomes in a real-world cohort. Methods: We identified 135 mCRPC pts treated with Ra-223 at our institution between 2013 and 2021. Pts who initiated another anti-tumor therapy within 60 days of Ra-223 treatment were excluded; pts continuing hormonal agents initiated &gt;60 days prior were included. ctDNA isolated from pre-treatment plasma underwent ultra-low-pass whole genome sequencing to estimate tumor fraction (TF). Additionally, targeted panel sequencing using an institutional prostate cancer-specific panel of 319 genes with duplex sequencing (utilizing unique molecular identifiers) for error suppression was used to identify germline or somatic deleterious alterations in HR pathway genes. The primary outcome was association between HRD status and completion of fewer than 6 cycles (as a proxy for early clinical progression), assessed using logistic regression. Results: The median age was 61 (IQR, 56-67) years, median pretreatment prostate-specific antigen (PSA) level was 26.2 (IQR, 8.1-84.1) ng/mL, and median TF was 4% (IQR, 3-6%). 97% of pts (n=131) previously received a novel antiandrogen, and 63% (n=85) received prior taxane. 17% (n=23) were HRD+, and 59% (n=80) completed 6 cycles of Ra-223. On multivariable analysis, HRD+ was associated with decreased likelihood of completing 6 cycles compared to HRD- (adjusted odds ratio [AOR] 0.16, 95% confidence interval [CI] 0.05-0.48, P=0.001). 22% (n=5) of HRD+ pts completed 6 cycles compared to 67% (n=75) of HRD- pts. Additional factors associated with decreased likelihood of completing 6 cycles included a higher pretreatment TF (AOR 0.69, 95% CI, 0.48-0.97, P=0.034) and prior taxane use (AOR 0.41, 95% CI, 0.18-0.91, P=0.028), but not pretreatment PSA ( P=0.574). Conclusions: Targeted panel sequencing with error suppression from ctDNA identified HRD+ in mCRPC pts with bone-predominant disease and low median TF at a similar frequency as reported from tissue. In our cohort, HRD+ was prognostic of early clinical progression with Ra-223. Further work is in progress to understand the association of other ctDNA-derived features, including assessment of genomic signatures and transcriptional binding sites, in the setting of Ra-223 therapy. DF/HCC IRB protocol 18-135.

Favorable Biochemical Freedom From Recurrence With Stereotactic Body Radiation Therapy for Intermediate and High-Risk Prostate Cancer: A Single Institutional Experience With Long-Term Follow-Up.

Purpose/Objective(s): The current study reports long-term overall survival (OS) and biochemical freedom from recurrence (BFFR) after stereotactic body radiation therapy (SBRT) for men with intermediate and high-risk prostate cancer in a single community hospital setting with early adoption.Materials/Methods: Ninety-seven consecutive men with intermediate and high-risk prostate cancer treated with SBRT between 2007 and 2015 were retrospectively studied. Categorical variables for analysis included National Comprehensive Cancer Network risk group, race, Gleason grade group, T stage, use of androgen deprivation therapy, and planning target volume dose. Continuous variables for analysis included pretreatment prostate-specific antigen (PSA), percent cores positive, age at diagnosis, PSA nadir, prostate volume, percent prostate that received 40 Gy, and minimum dose to 0.03 cc of prostate (Dmin). BFFR was assessed using the Phoenix nadir +2 definition. OS and BFFR were estimated using Kaplan–Meier (KM) methodology with comparisons accomplished using log-rank statistics. Multivariable analysis (MVA) was accomplished with a backwards selection Cox proportional-hazards model with statistical significance taken at the p < 0.05 level.Results: Median FU is 78.4 months. Five- and ten-year OS KM estimates are 90.9 and 73.2%, respectively, with 19 deaths recorded. MVA reveals pretreatment PSA (p = 0.032), percent prostate 40 Gy (p = 0.003), and race (p = 0.031) were predictive of OS. Five- and nine-year BFFR KM estimates are 92.1 and 87.5%, respectively, with 10 biochemical failures recorded. MVA revealed PSA nadir (p < 0.001) was the only factor predictive of BFFR. Specifically, for every one-unit increase in PSA nadir, there was a 4.2-fold increased odds of biochemical failure (HR = 4.248). No significant differences in BFFR were found between favorable intermediate, unfavorable intermediate, and high-risk prostate cancer (p = 0.054) with 7-year KM estimates of 96.6, 81.0, and 85.7%, respectively.Conclusions: Favorable OS and BFFR can be expected after SBRT for intermediate and high-risk prostate cancer with non-significant differences seen for BFFR between favorable intermediate, unfavorable intermediate, and high-risk groups. Our 5-year BFFR compares favorably with the HYPO-RT-PC trial of 84%. PSA nadir was predictive of biochemical failure. This study is ultimately limited by the small absolute number of high-risk patients included.

Comparison of Radiation Therapy and Radical Prostatectomy in the Treatment of High-Risk Prostate Cancer: A Retrospective Matched Pair Review

Both definitive radiation therapy (RT) ±androgen deprivation therapy (ADT) and radical prostatectomy (RP) + adjuvant RT±ADT are considered standard of care treatment regimens for patients with high risk prostate cancer. The ideal modality to treat this patient population and achieve disease control while also limiting treatment related toxicity remains debated. In this study, we utilized a retrospective matched pair analysis to compare survival and overall disease control outcomes relative to primary treatment modality. 1436 pts with National Comprehensive Cancer Network defined high risk prostate cancer diagnosed between August 1992 and October 2016 at a single institution were analyzed. All those eligible were treated with RP + adjuvant RT ±ADT (n=774) or definitive RT alone ±ADT (n=660), which consisted of either high dose rate (HDR) brachytherapy boost together with pelvic external beam RT (EBRT) or dose-escalated, adaptive radiation therapy (ART). A 1:1 matched pair analysis was completed, which paired 196 pts based on three poor prognostic characteristics: pre-treatment prostate-specific antigen (PSA) ≥ 20, Gleason score ≥ 8, and clinical T stage ≥T2c. There were 98 pts in both the RT and RP cohorts for this analysis. The average age of the RT and RP groups were 66.4 years and 66.7 years respectively. The median follow-up for those treated with RP was 13.6 years, while those treated with RT was 8.96 years. 21 (21.4%) treated with RP had ≥ T2c disease, while 37 (37.7%) treated with RT had ≥T2c disease. 40.8% in both the RP and RT cohorts had Gleason score ≥ 8. 37.8% of pts had a pre-treatment PSA ≥ 20 in both the RP and RT cohorts. 5 pts (5.1%) in both the RP and RT cohorts received ADT. 37 (37.7%) in the RT cohort were treated with HDR combined with EBRT, while 61 (62.2%) of the RT cohort were treated with ART. There was no statistical difference between pts treated with RT and those treated with RP for overall survival (p =0.21), cause specific survival (p=0.28), or distant disease control (p=0.88). RT was statistically superior compared to RP in regard to locoregional control (p=0.015). When analyzing the two modalities of RT used to treat high risk prostate cancer in this patient cohort compared to RP, both ART and HDR were statistically superior compared to RP in regard to locoregional disease control (p=0.049). Based on this retrospective matched pair analysis of 196 pts with high risk prostate cancer, the addition of radical prostatectomy to locoregional RT did not improve survival or locoregional disease control rates. Neither approach was associated with improved long-term survival, and locoregional disease control was superior in pts treated with definitive RT.

Is supplemental external beam radiation therapy necessary for patients with higher risk prostate cancer treated with 103Pd? Results of two prospective randomized trials.

To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 ((103)Pd) brachytherapy for high-risk prostate cancer patients. Trial 44/20 randomized patients to 44Gy plus 90Gy (103)Pd vs. 20Gy with 115Gy (103)Pd, and the subsequent trial randomized patients to the 20Gy arm vs. 125Gy (103)Pd without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes. In 44/20 trial, 13-year BF, prostate cancer-specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02ng/mL. With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort.

Clinical Characteristics and Outcome of Gleason Score 10 Prostate Cancer on Core Biopsy Treated by External Radiotherapy and Hormone Therapy.

To evaluate the clinical characteristics and outcomes of patients with Gleason score 10 prostate cancer treated by external radiotherapy and hormone therapy. From January 2003 to March 2014, 1832 patients with prostate cancer were treated, among which 9 patients (represented 0.49%) were identified as Gleason score 10 disease on prostate core biopsy without distant metastases when first diagnosed. All 9 patients were treated by whole pelvic external radiotherapy (The whole pelvic dose was 50.0 Gy and the boost dose ranged from 76.2 to 78.0 Gy) and long-term hormone therapy. We assessed the clinical characteristics, treatment outcomes and treatment toxicities. Survival curves were calculated using the Kaplan-Meier method. The median follow-up was 4.8 years. Six patients' pre-treatment prostate-specific antigen (PSA) levels were lower than 20.0 μg/L and three patients' pre-treatment PSA levels were higher than 70.0 μg/L. The median percentage of positive biopsy cores was 91%. Three, four and two cases were classified as T2c, T3a and T3b stage, respectively. Three cases were assessed as N1 stage. The 5-year biochemical failure-free survival, distant metastasis-free survival, cancer specific survival and overall survival rates were 28.6%, 57.1%, 66.7% and 57.1%, respectively. Five patients experienced grade 1-2 acute gastrointestinal toxicities and six patients complained of grade 1-2 acute genitourinary toxicities. No bone fracture or cardiovascular disease was detected. Gleason score 10 prostate cancer on core biopsy is usually combined with other high risk factors. The pre-treatment PSA levels lie in two extremes. Timely and active treatments are urgent needed because unfavourable oncological outcomes are often presented.

Pretreatment Tables Predicting Pathologic Stage of Locally Advanced Prostate Cancer

BackgroundPretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. ObjectiveTo construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. Design, setting, and participantsThis was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. InterventionRetropubic RP and pelvic lymphadenectomy. Outcome measurements and statistical analysisPatients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. Results and limitationsIn the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. ConclusionsThese novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Patient summaryOur study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.

Outcomes and predictors of localized or locally-advanced prostate cancer treated by radiotherapy in Indonesia

Purpose:Presently there is no published data on the outcomes of localized or locally-advanced prostate cancer (PCa) treated by external-beam radiotherapy (RT) in Indonesia.Methods:This study retrospectively analyzed 96 patients with localized or locally-advanced PCa treated by RT from year 1995 to 2009, at the national referral hospital and the national cancer hospital of Indonesia. Cumulative prostate and pelvic radiation dose/type was <70 Gy conventional RT in 84.4% patients, and ≥70 Gy Three dimensional-conformal or intensity modulated RT in 15.6% patients. Overall survival (OS) and biochemical progression-free survival (BFS) were estimated by Kaplan-Meier. Predictors of OS and biochemical recurrence were analyzed by multivariate Cox regressions.Results:The median follow-up was 61 months (range, 24 to 169 months). There were 3.1% low-risk, 26% intermediate-risk, and 70.8% high-risk cases. More than half of the patients (52.1%) had pretreatment prostate-specific antigen (PSA) >20 ng/mL. The 5-year survival outcome of low-risk, intermediate-risk, and high-risk patients were: OS, 100%, 94.7%, and 67.9% (P=0.297); and BFS, 100%, 94.1%, and 57.1% (P=0.016), respectively. In the high-risk group, the 5-year OS was 88.3% in patients who received adjuvant hormonal androgen deprivation therapy (HT), compared to 53% in RT only, P=0.08. Significant predictors of OS include high-risk group (hazard Ratio [HR], 9.35; 95% confidence interval [CI], 1.52 to 57.6; P=0.016), adjuvant therapy (HR, 0.175; 95% CI, 0.05 to 0.58; P=0.005), detection by transurethral resection of the prostate (TUR-P) (HR, 6.81; 95% CI, 2.28 to 20.33; P=0.001), and pretreatment PSA (HR, 1.003; 95% CI, 1.00 to 1.005; P=0.039). The sole predictor of biochemical failure was pretreatment PSA (P=0.04), with odds ratio of 4.52 (95% CI, 1.61 to 12.65) for PSA >20 ng/mL.Conclusions:RT is an effective treatment modality for localized or locally-advanced PCa in Indonesian patients, with outcomes and predictors consistent to that reported elsewhere. Predictors of poorer outcomes include high-risk group, higher pretreatment PSA, incidental detection by TUR-P, and lack of adjuvant HT. Adjuvant hormonal therapy significantly improve the survival of high risk patients.

Salvage radiotherapy for prostate cancer

Purpose: Recent modeling efforts, based on reported outcomes following salvage radiotherapy (SRT) for prostate cancer, predict the likelihood of biochemical control (tumor control probability, TCP) as a function of pre-treatment prostate specific antigen (PSA) and SRT dose. Similar instruments predict the risk of grade ≥ 3 late toxicity (normal tissue complication probability, NTCP) as a function of SRT dose. Here we explore how changes in the parameters of those models might affect the optimal SRT dose and clinical outcomes. Materials and Methods: Baseline TCP and NTCP model parameters were established in a previous report. Pre-treatment PSA was set at 0.4 ng/mL. Model parameters were modified to explore four scenarios: (1) improving the safety of SRT, (2) increasing tumor cell radiosensitivity, (3) increasing the cure rate achievable with SRT and (4) adoption of hypofractionated SRT schedules. The “optimal” SRT dose, defined as the dose that maximized the likelihood of achieving biochemical control without causing late toxicity, was identified for each scenario. Results: Improving the safety of SRT increased the optimal SRT dose, while radiosensitization decreased the optimal dose. Both changes were predicted to increase the probability of biochemical control and decrease late toxicity rates. Increasing the cure rate achievable with SRT (eg: improving patient selection or combining SRT with effective systemic therapy) provided the greatest gains in TCP. Adoption of a hypofractionated SRT schedule was predicted to improve both biochemical control and late toxicity. Conclusions: Modeling exercises demonstrate the significant gains that may be achieved with improved implementation of SRT for prostate cancer. Strategies to realize the effects modeled in this report should be explored in clinical trials.

Outcomes of salvage prostate cryotherapy stratified by pre-treatment PSA: update from the COLD registry

In this study, we evaluate the outcomes of salvage cryotherapy for locally recurrent prostate cancer within the COLD (cryo online data) Registry. Furthermore, we assess the results of salvage cryotherapy (with intermediate follow-up) stratified by pre-treatment prostate-specific antigen (PSA) levels to determine which patients may best be suited for treatment. The COLD registry was developed as a prospective, centrally collected database among patients undergoing salvage cryoablation for locally recurrent prostate cancer following primary prostate radiotherapy with curative intent. Of the patients undergoing salvage cryotherapy (without neoadjuvant hormonal ablative therapy), complete medical records were available in 156 patients, with their mean follow-up being 3.8 years (0.9-12.7 years). The treatment outcomes of salvage cryotherapy were assessed using the Phoenix definition (nadir PSA + 2 ng/ml) of biochemical failure. Of our entire study population, the biochemical disease-free survival (bDFS) rates at 1, 2, and 3 years were 89.0, 73.7, and 66.7%, respectively. Stratification of our patients into two subgroups is based on their pre-treatment total serum PSA values <5 and ≥5 ng/ml, and bDFS rates at 3 years for these two subgroups were 78.3 and 52.9%, respectively. A Kaplan-Meier analysis of bDFS stratified by these same pre-treatment PSA values revealed that the subset of patients with a PSA ≥ 5 ng/ml had statistically significant poorer bDFS rates (P = 0.01). Salvage prostate cryotherapy is a potentially curative local salvage therapy. The importance of early referral when patients have a pre-treatment PSA < 5 ng/ml is essential to optimize treatment outcomes.

Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes

BackgroundHigher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. ObjectiveIdentify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participantsThis retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. InterventionPrescription doses ranged from 64.8 to 86.4Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. MeasurementsA proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitationsRadiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels <70.2Gy and 70.2–79.2Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse–free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. ConclusionsHigher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.

Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: A retrospective study from the view point of new 2010 anatomic stage/prognostic groups

The expression of Hedgehog (Hh) signaling pathway in prostate cancer is well-known but its clinicopathologic role has not been elucidated well. Prostatectomy cases of prostate cancer (n=155) were prepared and assessed by clinicopathologic parameters including new 2010 anatomic stage/prognostic groups (ASPG) of prostate cancer. The expression of five Hh signaling proteins including Sonic hedgehog (Shh), Patched, Smoothened, and GLIoma-associated oncogene, in addition with Suppressor of fused (Su(fu)) were analyzed immunohistochemically. Real-time polymerase chain reaction was performed to assess the mRNA expression status. The expression of each Hh signaling protein was significantly correlated with poor prognostic parameters such as larger tumor size, high pretreatment prostate-specific antigen (PSA), high Gleason score, perineural invasion and new ASPG. Among Hh signaling proteins, Sonic hedgehog and Smoothened expressions tend to have a significantly higher risk of PSA recurrence (P<0.001 and P=0.011, respectively). Multivariate analysis proved Shh expression as independent prognostic factors of PSA recurrence along with Gleason score, ASPG, tumor volume, and pretreatment PSA. Hh signaling activity is significantly associated with worse prognostic parameters. Shh can be regarded as a poor prognostic factor for PSA recurrence.

886 LONG-TERM SURVIVAL AFTER SURGERY VERSUS EXTERNAL BEAM RADIOTHERAPY FOR HIGH-RISK PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: The management of patients with high-risk prostate cancer remains in debate, and prospective clinical trials comparing treatment outcomes are lacking. We evaluated the survival of patients with high-risk disease following radical prostatectomy (RP) and external beam radiation therapy (RT) during the PSA era. METHODS: We identified 1,238 men who underwent RP and 609 men treated with RT between 1988–2004 who had a pretreatment prostate specific antigen (PSA) 20 ng/mL, biopsy Gleason score 8–10, or clinical stage T3. The impact of treatment modality on cancer-specific (CSS) and overall survival (OS) was analyzed using Cox proportional hazard regression models controlling for patient age, Charlson comorbidity index (CCI), and clinicopathologic tumor variables. RESULTS: Patients treated with RT were older (p 0.0001), had a greater pretreatment PSA (p 0.02), higher biopsy Gleason score (p 0.0001), and more advanced clinical stage (p 0.0001). In total, 344 (57%) men who underwent RT were treated with adjuvant androgen deprivation therapy (ADT), while 418 (34%) men who underwent RP received adjuvant ADT and 136 (11%) received adjuvant RT. Median follow-up was 10.2, 6.0, and 7.2 years after RP, RT ADT, and RT alone. Estimated 10-year CSS following RP and RT ADT was equivalent (92%), and was modestly better than RT alone (88%; p 0.06). 10-year OS was significantly improved after RP (77%) versus RT ADT (67%) or RT alone (52%; p 0.001). On multivariate analysis (Table), patients who underwent RT alone had a significantly increased risk of death from prostate cancer (p 0.0006) and overall mortality (p 0.0001) compared to patients treated with RP. No significant difference in the risk of cancer death was seen between RT ADT and RP (p 0.90); however, men who received RT ADT had a greater than 50% increased risk of overall mortality versus men who underwent RP (p 0.0005). CONCLUSIONS: RP and RT ADT provide similar long-term cancer control for patients with high-risk disease, although the risk of all-cause mortality was greater after RT ADT. As surgery provides pathologic staging to guide the selected use of secondary therapies, prospective studies evaluating the differing impact of treatments on quality of life and non-cancer mortality are necessary to determine the optimal management approach to these men.

Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer

It has not been elucidated whether certain types of M1b prostate cancer (M1b PC) are associated with a poor outcome. The present study retrospectively identified predictive factors related to the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC. The observation period ranged from 4 to 122 months (median, 43 months). The parameters investigated were: T classification, N classification, Gleason score (GS), pretreatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium, and hemoglobin (Hb) levels, platelet count, and the status of HER-2 overexpression as determined with a Hercep Test(TM) Kit using initial needle biopsy specimens for diagnosis. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pretreatment PSA ≥ 192, N1, GS ≥ 8, EOD grade 3+4, high LDH, high ALP, low Hb, and HER-2 overexpression. Multivariate Cox proportional hazard analysis identified the factors GS ≥ 8, high LDH, and HER-2 overexpression with significant differences. The hazard ratio was 5.962, 2.465, and 2.907, respectively, and the probability value was P=0.0218, P=0.0207 and P=0.0090, respectively. When the subjects with GS ≥ 8, high LDH, and HER-2 over-expression were classified as the high-risk group, the 5-year cause-specific survival rate was 51.2, 29.6, and 20.0%, respectively. The present study showed that M1b PC patients with GS ≥ 8, high LDH, and HER-2 overexpression have a very poor outcome and thus, should be treated as a high-risk group requiring close follow-up.

Correlation between Chemokine Receptor CXCR4 Expression and Prognostic Factors in Patients with Prostate Cancer

PurposeWe evaluated the correlation between the expression of CXCR4 and prognostic factors in patients with prostate cancer.Materials and MethodsA total of 57 patients who had undergone surgery for prostate cancer were enrolled. Specimens were obtained before any treatment and were stained with antihuman CXCR4 antibody. The intensity of staining was graded as low or high. The age, pretreatment prostate-specific antigen (PSA) level, Gleason score, T stage, biochemical recurrence, local recurrence, and distant metastasis were compared according to the expression of CXCR4 in patients with prostate cancer.ResultsLocal recurrence was higher in the group with high expression, in 11 of 36 cases (30.6%), than in the group with low expression, in 1 of 21 cases (4.8%), with statistical significance (p=0.040). Distant metastasis was also associated with expression, occurring in 10 of 36 cases (27.8%) in the group with high expression and in 1 of 21 cases (4.8%) in the group with low expression (p=0.041). In the logistic regression test, CXCR4 expression was the only factor in determining local recurrence (p=0.016) and distant metastasis (0.022). Furthermore, the group with high CXCR4 expression showed significantly longer cancer-specific survival than did the low expression group (p=0.041). CXCR4 showed no association with age (p=0.881), pretreatment PSA level (p=0.584), Gleason score (p=0.640), T stage (p=0.967), or biochemical recurrence (p=0.081).ConclusionsThe high expression of CXCR4 was associated with local recurrence and distant metastasis. CXCR4 expression was shown to be a useful prognostic factor for patients with prostate cancer.

Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score>7 (p=0.001), pretreatment prostate-specific antigen (PSA) level>20 ng/mL (p=0.037), higher radiation dose (p=0.005), and the use of adjuvant LTAD vs. STAD (p=0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose>78 Gy was 97%. For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum>7 and pretreatment PSA level>20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with addition of novel agents.

Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

Investigation of risk factors for prostate cancer patients with bone metastasis based on clinical data.

It has not yet been determined whether certain types of prostate cancer with bone metastasis (M1b PC) are associated with a poor outcome. The present study retrospectively assessed the potential significance of various clinical data in predicting the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC between January 1998 and December 2006. The age of the subjects ranged from 51 to 91 years (median 74). The observation period ranged from 4 to 122 months (median 43). The parameters investigated were T classification, N classification, Gleason score (GS), pre-treatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium and hemoglobin (Hb) levels and platelet count. The 5-year cause-specific survival rate was 56.6% and the 10-year cause-specific survival rate was 34.9%. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pre-treatment PSA level ≥192, N1, GS ≥8, EOD grade 3+4, high LDH, high ALP and low Hb. Multivariate Cox proportional hazard analysis identified the factors GS ≥8 and high LDH with significant differences. The hazard ratio was 4.967 and 2.728, respectively, and the probability value (P) was 0.029 and 0.004, respectively. When the subjects with GS ≥8 and high LDH were classified as the high-risk group, the 5-year cause-specific survival rate was 24.6%. The outcome was significantly poorer in this group (P<0.0001) than in the other group, which had a 5-year cause-specific survival rate of 67.7%. The present study showed that patients with M1b PC with GS ≥8 and high LDH have a very poor outcome and thus should be treated as a high-risk group requiring close follow-up.

Editorial Comment

No AccessJournal of UrologyAdult Urology1 Jan 2010Editorial Comment H. Ballentine Carter H. Ballentine CarterH. Ballentine Carter More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.08.219AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, 183(1), pp. 116–117 References 1 : Clinical decisions. N Engl J Med2008; 359: 2607. Google Scholar 2 : Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy. J Clin Oncol2009; 27: 3591. Google Scholar Department of Urology, The Johns Hopkins School of Medicine, Baltimore, Maryland© 2010 by American Urological AssociationFiguresReferencesRelatedDetails Volume 183Issue 1January 2010Page: 116-117 Advertisement Copyright & Permissions© 2010 by American Urological AssociationMetricsAuthor Information H. Ballentine Carter More articles by this author Expand All Advertisement PDF downloadLoading ...

Pretreatment Prostate-Specific Antigen (PSA) Velocity and Doubling Time Are Associated With Outcome but Neither Improves Prediction of Outcome Beyond Pretreatment PSA Alone in Patients Treated With Radical Prostatectomy

Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model. The cohort included 2,938 patients with two or more PSA values before radical prostatectomy. Biochemical recurrence (BCR) occurred in 384 patients, and metastases occurred in 63 patients. Median follow-up for patients without BCR was 2.1 years. We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis. Predictive accuracy was assessed using the concordance index. On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P < .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.