Cancer Biochemical Recurrence Research Articles

Learning to predict prostate cancer recurrence from tissue images

Roughly 30% of men with prostate cancer who undergo radical prostatectomy will suffer biochemical cancer recurrence (BCR). Accurately predicting which patients will experience BCR could identify who would benefit from increased surveillance or adjuvant therapy. Unfortunately, no current method can effectively predict this. We develop and evaluate PathCLR, a novel semi-supervised method that learns a model that can use hematoxylin and eosin (H&E)-stained tissue microarrays (TMAs) to predict prostate cancer recurrence within 5 years after diagnosis. The learning process involves 2 sequential steps: PathCLR (a) first employs self-supervised learning to generate effective feature representations of the input images, then (b) feeds these learned features into a fully supervised neural network classifier to learn a model for predicting BCR. We conducted training and evaluation using 2 large prostate cancer datasets: (1) the Cooperative Prostate Cancer Tissue Resource (CPCTR) with 374 patients, including 189 who experienced BCR, and (2) the Johns Hopkins University (JHU) prostate cancer dataset of 646 patients, with 451 patients having BCR. PathCLR’s (10-fold cross-validation) F1 score was 0.61 for CPCTR and 0.85 for JHU. This was statistically superior (paired t-test with P <.05) to the best-learned model that relied solely on clinicopathological features, including PSA level, primary and secondary Gleason Grade, etc. We attribute the improvement of PathCLR over models using only clinicopathological features to its utilization of both learned latent representations of tissue core images and clinicopathological features. This finding suggests that there is essential predictive information in tissue images at the time of surgery that goes beyond the knowledge obtained from reported clinicopathological features, helping predict the patient’s 5-year outcome.

Genetic variant located on chromosome 17p12 contributes to prostate cancer onset and biochemical recurrence

The genetic contribution to prostate cancer (PC) onset and clinical heterogeneity has an important impact on the disease stratification accuracy. Despite the fact that radical prostatectomy (RP) is an effective treatment for localized PC, a considerable number of individuals develop biochemical recurrence (BCR) following surgery. In the present study, we decided to investigate the significance of genetic variability in a homogeneous group of Romanian men and to determine if genotyping could provide information regarding the possible implications of rs4054823 susceptibility loci in PC progression and outcome. A total of 78 samples from both PC and benign prostatic hyperplasia (BPH) patients were genotyped. The genotype frequencies were examined to see if there was a link between the 17p12 SNP and PC disease. When compared to the BPH group, the PC group had a significantly higher frequency of the T risk variant (P = 0.0056) and TT genotype (P = 0.0164). Subsequent analysis revealed that the TT genotype had a significantly higher frequency among younger PC patients based on their age at diagnosis and that it was related with a greater probability of BCR (P = 0.02). According to our findings, the TT genotype appears to be a risk factor for early-onset PC and a potential predictor for BCR after RP.

Perineural invasion on biopsy specimen as predictor of tumor progression in aging male treated with radical prostatectomy. Could we use it for pre-surgical screening?

We aimed to analyze the correlation of perineural invasion on transrectal ultrasound guided prostate biopsy with predictors of biochemical cancer recurrence, as well as its impact on clinical outcomes, for non-metastatic prostate cancer. For the study, patients with perineural invasion (N = 86) were recruited into group I and underwent open retropubic prostatectomy, regardless of clinical stage; cases with prostate cancer but without perineural invasion on biopsy, who received radical prostatectomy as the treatment modality, were placed into group II (n = 90). Perineural invasion was detected preoperatively in 43% of cases that revealed surgical margin positivity postoperatively, while 85% of the remaining cases (group II) had negative surgical margins. There was no correlation on prostate biopsy between perineural invasion and Gleason score or PSA, based on Sperman’s rank-order correlation analysis. However, there was strong positive correlation of perineural invasion with clinical stage and patients age. Additionaly, we demonstrated that perineural invasion on biopsy is a non-independent risk factor for metastatic occurrence, although the correlation was significant in univariate analysis. Nevertheless, we found strong correlation between invasion on initial biopsy specimen with biochemical cancer recurrence, suggesting that perineural invasion on prostate biopsy is a significant predictor of worse prognostic outcome.

Randomized phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT

TPS136 Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) biochemical recurrence (BCR) after radical prostatectomy (RP) is commonly initiated in patients with PSA &lt; 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. The purpose of this randomized phase 3 trial is to evaluate the success rate of SRT for PCa BCR after RP with and without planning based on 68Ga-PSMA-11 PET/CT (PSMA). Here we present the study protocol. Methods: This is an interventional phase 3 randomized prospective open label clinical trial with parallel assignment designed for superiority. Patients who are planned to undergo SRT for PCa BCR with PSA &gt; 0.1 ng/ml are eligible. The choice of treating the prostate bed with/without pelvic lymph nodes, with/without androgen deprivation therapy, is left to the discretion of the treating radiation oncologist (RO). RO may or may not change the RT plan depending on the PSMA findings. Any other imaging is allowed for SRT planning if done per routine care. The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (PFS) after initiation of SRT. Biochemical progression is defined by PSA≥0.2 ng/mL and rising. Based on literature data we hypothesized that 1) the incorporation of PSMA to SRT planning will improve 5-year PFS by 20%, 2) the 5-year PFS will be 60% in standard Arm 1 and 80% in interventional Arm 2, and 3) 13% of subjects randomized to Arm 2 will have extra-pelvic metastasis detected by PSMA and will not be included in analysis of the primary endpoint. We will randomize 193 patients (1:1.13 ratio) to proceed with standard SRT (n = 90) or undergo PSMA scan (free of charge for patients) prior SRT planning (n = 103). Patients will be followed for 5 years after the date of initiation of SRT. Discussion: Main pitfalls in study design include 1) drop-out of patients randomized to the control arm and 2) potential FDA approval of PSMA PET imaging probes in the near future (no randomization to standard arm would be then acceptable). This is the first prospective randomized phase 3 trial designed to determine whether PET/CT can improve outcome of SRT in patients with BCR. Clinical trial information: NCT03582774.

Low-cost thermophoretic profiling of extracellular-vesicle surface proteins for the early detection and classification of cancers.

Non-invasive assays for early cancer screening are hampered by challenges in the isolation and profiling of circulating biomarkers. Here, we show that surface proteins from serum extracellular vesicles labelled with a panel of seven fluorescent aptamers can be profiled, via thermophoretic enrichment and linear discriminant analysis, for cancer detection and classification. In a cohort of 102 patients, including 6 cancer types at stages I-IV, the assay detected stage I cancers with 95% sensitivity (95% confidence interval (CI): 74-100%) and 100% specificity (95% CI: 80-100%), and classified the cancer type with an overall accuracy of 68% (95% CI: 59-77%). For patients who underwent prostate biopsies, the assay was superior to the analysis of prostate-specific antigen levels (area under the curve: 0.94 versus 0.68; 33 patients) for the discrimination of prostate cancer and benign prostate enlargement, and also in the assessment of biochemical cancer recurrence after radical prostatectomy. The assay is inexpensive, fast, and requires small serum volumes (<1 µl), and if validated in larger cohorts may facilitate cancer screening, classification and monitoring.

Modification of biochemical recurrence risk in patients with localized prostate cancer after radical prostatectomy with combined histomorphological changes in the peritumoral zone

Aim. To assess the prognostic significance of histopathological processes in the peritumoral zone with respect to the risk of biochemical recurrence in patients with localized prostate cancer after radical prostatectomy. Methods. Histomorphological studies were conducted in the perifocal area of surgical tissue samples from 309 patients with localized prostate cancer (T1c-2cN0M0) after a radical surgery using light microscopy. Four groups of patients were identified depending on the risk of recurrence. Enzyme immunoassay was used to determine the concentration of prostate-specific antigen in the serum at baseline and every 3 months for two years after the surgery to detect biochemical recurrence. Results. Histomorphological examination of the peritumoral zone made it possible to identify histopathological processes associated with adenocarcinoma in 257 out of 309 (83.2%) patients with localized prostate cancer. The risk of biochemical recurrence of a combination of prostatic adenocarcinoma and prostatic intraepithelial neoplasia-2 increased by 3.3 (p=0.02), and of a combination of adenocarcinoma, neoplasia and chronic inflammation in the perifocal zone increased by 4.5 times (p=0.005) compared to patients without histopathological changes of the peritumoral zone. In combination of prostate adenocarcinoma with neoplasia and chronic inflammation in the peritumoral zone, the number of patients with an intermediate risk of cancer recurrence after surgical treatment increased due to decrease of the proportion of patients with very low and low risk of recurrence of the oncologic disease. Conclusion. The combination of prostate cancer with high-grade prostatic intraepithelial neoplasia and chronic inflammation in the peritumoral zone modifies the risk of biochemical recurrence of cancer after radical prostatectomy.

The relationship between anxiety about prostate cancer among patients with biochemical cancer recurrence and the use of complementary and alternative medicines, diet, and exercise

Objective We aimed to explore associations between anxiety and specific health behaviors such as complementary and alternative medicine (CAM), diet, and exercise among prostate cancer patients. Methods PCa patients enrolled in a prospective cohort study of men with biochemical cancer recurrence were surveyed about use of CAM, diet, and exercise. Anxiety was measured with the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and the anxiety subscale of the Hospital Anxiety and Depression Scale. Results Nearly 70% (44 of 67) of the original cohort of patients completed the supplementary CAM survey. The mean age was 68 years. Eighty percent of respondents reported engaging in a relevant health behavior, and 64% reported doing so in direct response to their PCa diagnosis. Overall, the most prevalent specific behaviors were exercising (56%), making dietary changes (50%), taking calcium supplements (41%), and taking vitamin D supplements (39%). Elevated baseline PCa-specific anxiety (MAX-PC score >16) after biochemical cancer recurrence was associated with use of any CAM (P=0.01), use of herbs/supplements (P=0.01), and dietary changes (P=0.04). Conclusion PCa patients commonly use CAM, dietary changes, and exercise in response to their diagnosis, and these changes are associated with elevated general and PCa-specific anxiety.

A combination of computer extracted measurements of prostate capsule shape and tumor texture on MRI to predict biochemical recurrence post treatment.

e16554 Background: Prostate cancer (PCa) biochemical recurrence (BCR) occurs in a significant proportion of men after treatment and is associated with increased mortality. Identifying PCa patients at risk of BCR following definitive therapy may help identify patients who might benefit from adjuvant therapy. Multi-parametric MRI (mpMRI) is being increasingly used in pre-treatment staging and risk stratification of PCa. In this work, we sought to explore whether a combination of computer extracted features relating to prostate capsule shape and tumor texture from pre-treatment mpMRI is predictive of BCR post treatment. Methods: This single center and retrospective study included 80 men with PCa who underwent pre-treatment 3T mpMRI and were followed for &gt; 3 years post treatment. These men were grouped into a training set D1 (N = 50, 25 each of BCR+ and BCR-) and an independent validation set D2 (N = 30, 10 BCR+ and 20 BCR-). The prostate capsule and cancer region of interest (ROI) were annotated on mpMRI by a single experienced radiologist. Shape features (curvature and orientation) were extracted from a surface of interest where statistically significant differences were observed between BCR+ and BCR- patients in the training set. Radiomic features for capturing tumor textural patterns (including 1st and 2nd order statistics, Gabor and Haralick) were extracted from within the radiologist annotated cancer ROIs. Features from D1 were used to train random forest classifiers, one each with shape (Cs) and radiomic (CR) features. A fused Bayesian classifier (CR+S) was created by integrating decisions from both Cs and CR. Results: The classifiers Cs, CR and CR+S were evaluated on independent validation set D2, resulting in area under the curve (AUCs) of 0.71, 0.81 and 0.84 respectively. Cs added value in patients who had extra prostatic spread of PCa, but suffered from mpMRI intensity artefacts that affected performance of CR. Conclusions: Integrating prostate capsule shape and tumor radiomic features from pre-treatment mpMRI enabled prediction of PCa BCR after treatment. Multi-site validation is needed to establish the robustness of the approach.

Akt Activation Correlates with Snail Expression and Potentially Determines the Recurrence of Prostate Cancer in Patients at Stage T2 after a Radical Prostatectomy

Our previous work demonstrated the epithelial-mesenchymal transition factor, Snail, is a potential marker for predicting the recurrence of localized prostate cancer (PCa). Akt activation is important for Snail stabilization and transcription in PCa. The purpose of this study was to retrospectively investigate the relationship between the phosphorylated level of Akt (p-Akt) in radical prostatectomy (RP) specimens and cancer biochemical recurrence (BCR). Using a tissue microarray and immunohistochemistry, the expression of p-Akt was measured in benign and neoplastic tissues from RP specimens in 53 patients whose cancer was pathologically defined as T2 without positive margins. Herein, we observed that the p-Akt level was higher in PCa than in benign tissues and was significantly associated with the Snail level. A high p-Akt image score (≥8) was significantly correlated with a higher histological Gleason sum, Snail image score, and preoperative prostate-specific antigen (PSA) value. Moreover, the high p-Akt image score and Gleason score sum (≥7) showed similar discriminatory abilities for BCR according to a receiver-operator characteristic curve analysis and were correlated with worse recurrence-free survival according to a log-rank test (p < 0.05). To further determine whether a high p-Akt image score could predict the risk of BCR, a Cox proportional hazard model showed that only a high p-Akt image score (hazard ratio (HR): 3.12, p = 0.05) and a high Gleason score sum (≥7) (HR: 1.18, p = 0.05) but not a high preoperative PSA value (HR: 0.62, p = 0.57) were significantly associated with a higher risk of developing BCR. Our data indicate that, for localized PCa patients after an RP, p-Akt can serve as a potential prognostic marker that improves predictions of BCR-free survival.

Weight Management to Reduce Prostate Cancer Risk: A Survey of Men's Needs and Interests.

Obese men have a higher rate of prostate cancer-related death than non-obese men, and obesity increases the risk of prostate cancer progression and biochemical recurrence. The purpose of this study was to assess needs and interests of men for a technology-driven weight loss intervention to reduce prostate cancer risk. We distributed a survey collecting demographic characteristics, health history, exercise and eating habits (and perception of those habits), current and prior attempts of health behavior change, and technology use. Survey answers were summarized by count and percent of total respondents. Completed surveys (N = 109) described men with a family history of prostate cancer (25%), a history of elevated prostate specific antigen (26%), and prostate cancer survivors (22%). We compared body mass index (BMI) to perception of weight; overweight and obese men perceived their weight as more normal than their BMI category suggests. Most men reported their diet needed minor improvement (74%), and 65% of men reported they are either currently trying to lose weight or interested in weight loss. Most respondents access the internet (92%), while text messaging (60%) and smartphone application use (40%) are less frequent, especially in men over 60. Our results revealed a need and willingness for lifestyle modification and suggest a need for evidence-based weight loss strategies and for addressing the misperception of weight status. A male-tailored intervention that implements technology could improve energy balance, hold men accountable to healthy behavior change, and promote dietary patterns in order to reduce prostate cancer risk.

Penile rehabilitation and cancer spread.

This year, the Editorial Board has given much attention to convergence. By systematically combining diverse fields of study, efforts have been made to overcome the limitations of existing interpretations. The convergent status of rehabilitation exercises and the need to overcome medical and societal problems through convergence, which was emphasized during the MERS (Middle East respiratory syndrome) outbreak, were introduced. Now, in the last issue of the year, we reconsider the concept of penile rehabilitation, which has until now been recognized as safe. We suggest an urgent need to conduct high-quality prospective studies with regard to the biochemical recurrence of cancer, specifically with regard to the mechanism by which phosphodiesterase type 5 inhibitors (PDE5I) may affect the course of prostate cancer when taken after radical prostatectomy. Drugs like Viagra and Cialis work by deactivating the enzyme PDE5-a chemical that takes away an erection after sex by limiting blood supply. However, scientists now think that malignant melanoma is fueled by a faulty gene (a family of serine-threonine protein kinases, BRAF) which suppresses the enzyme PDE5, suggesting that PDE5 plays an important role in preventing the spread of cancer cells, including prostate cancer cells. It is feared that Viagra, and drugs like it, could be mimicking the effect of the mutated BRAF gene. The early administration of PDE5I after radical prostatectomy is helpful in the patient’s fast recovery of erectile function, and it is often used clinically as a means of penile rehabilitation. However, according to one recent retrospective analysis of patients who received bilateral nerve-sparing radical prostatectomy, it was suggested that taking PDE5I might be associated with the biochemical recurrence of prostate cancer (Loeb et al., 2015; Michl et al., 2015). Hence, the relationship between PDE5I medication and the biochemical recurrence of prostate cancer needs to be reviewed, based on reports of the impact of PDE5I on prostate cancer progression in prospective studies that used PDE5I for the purpose of penile rehabilitation after radical prostatectomy. By using data up to December 2014 from PubMed, Embase, and the Cochrane Library, a search was performed for prospective case-control studies evaluating the effects of PDE5I intake after radical prostatectomy on erectile dysfunction. From the selected studies, comparisons were made according to the surgical method for prostate cancer, the type and administration method of PDE5I, the method for evaluating erectile functionality, and adverse events (Gallina et al., 2015; Li et al., 2014; Vehmas, 2015). All 15 randomized prospective studies investigated nerve-sparing radical prostatectomy patients; in 12 studies, the patients underwent bilateral nerve-sparing surgery and in three studies, the patients underwent unilateral nerve sparing. In terms of the type of PDE5I, sildenafil was used in seven studies, tadalafil was used in seven, and vardenafil was used in one. In 11 of the studies, patients were administered PDE5I every day after nerve-sparing radical prostatectomy, and in four studies patients were only administered PDE5I as needed. Questionnaires used to assess erectile function included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile, the Sexual Health Inventory for Men, and the Erectile Dysfunction Inventory of Treatment Satisfaction. The IIEF was used in all but two studies, either by itself or together with other instruments. Complications after the administration of PDE5I were observed in seven of the 15 studies, and these were mild complications such as headaches, indigestion, hot flashes, and nasopharyngitis. The remaining six studies did not include information on safety and complications of PDE5I intake after surgery. There were no studies that reported follow-up monitoring of prostate cancer after radical prostatectomy. Studies to date have only focused on the therapeutic effects of PDE5I in restoring erectile functionality, and studies on the effects of PDE5I on prostate cancer are lacking. It is currently not possible to perform a meta-analysis. Therefore, there is a need for further prospective case-control studies on the association of biochemical recurrence of prostate cancer with the intake of PDE5I after radical prostatectomy. Next year, JER aims to look even closer at rehabilitation-related assessments from different academic perspectives and to introduce these interests to readers.

Blood Storage Duration and Biochemical Recurrence of Cancer After Radical Prostatectomy

To test the hypothesis that perioperative transfusion of allogeneic and autologous red blood cells (RBCs) stored for a prolonged period speeds biochemical recurrence of prostate cancer after prostatectomy. We evaluated biochemical prostate cancer recurrence in men who had undergone radical prostatectomy and perioperative blood transfusions from July 6, 1998, through December 27, 2007. Those who received allogeneic blood transfusions were assigned to nonoverlapping "younger," "middle," and "older" RBC storage duration groups. Those who received autologous RBC transfusions were analyzed using the maximum storage duration as the primary exposure. We evaluated the association between RBC storage duration and biochemical recurrence using multivariable Cox proportional hazards regression. A total of 405 patients received allogeneic transfusions. At 5 years, the biochemical recurrence-free survival rate was 74%, 71%, and 76% for patients who received younger, middle, and older RBCs, respectively; our Cox model indicated no significant differences in biochemical recurrence rates between the groups (P=.82; Wald test). Among patients who received autologous transfusions (n=350), maximum RBC age was not significantly associated with biochemical cancer recurrence (P=.95). At 5 years, the biochemical recurrence-free survival rate was 85% and 81% for patients who received younger and older than 21-day-old RBCs, respectively. In patients undergoing radical prostatectomy who require RBC transfusion, recurrence risk does not appear to be independently associated with blood storage duration.

Racial Disparities in Prostate Cancer Incidence, Biochemical Recurrence, and Mortality

Racial Disparities in Prostate Cancer Incidence, Biochemical Recurrence, and Mortality

Lifelong Yearly Prostate Specific Antigen Surveillance is Not Necessary for Low Risk Prostate Cancer Treated With Radical Prostatectomy

Many patients undergoing radical prostatectomy in the prostate specific antigen era have a low risk of recurrence. Aggressive postoperative prostate specific antigen surveillance is costly and anxiety provoking. In this study we investigate the need for yearly prostate specific antigen measurements in patients with surgically treated low risk prostate cancer. We identified 2,219 patients who underwent radical prostatectomy between 1994 and 2004 for low risk localized prostate cancer. Low risk was defined as prostate specific antigen less than 10 ng/ml, pathological stage pT2c or less, Gleason score 6 or less, negative lymph nodes and negative surgical margins. Patients who underwent neoadjuvant or adjuvant therapy were excluded from analysis. Biochemical failure was defined as a prostate specific antigen greater than 0.4 ng/ml and prostate specific antigen values less than 0.15 ng/ml were considered undetectable. Biochemical failure rates were calculated according to the duration of the prostate specific antigen-free period after radical prostatectomy. A total of 142 (6.4%) patients experienced biochemical failure during the course of the study. The risk of biochemical failure decreased with increasing duration of the prostate specific antigen-free interval. For example 1, 3 and 5-year biochemical failure rates calculated at surgery were 1.8%, 4.2% and 6.3%, respectively. For patients with undetectable prostate specific antigen measurements 5 years after surgery the 1, 3 and 5-year biochemical failure rates were 0.0%, 0.7% and 1.3%, respectively. In addition, 1-year biochemical failure rates were 0.2%, 0.4%, 0.0% and 0.0% after a prostate specific antigen-free period of 1, 3, 5 and 10 years, respectively. The risk of biochemical failure is inversely proportional to the duration of the prostate specific antigen-free interval after radical prostatectomy in low risk patients. Biochemical failure 1 year after an undetectable prostate specific antigen is uncommon, especially after a prostate specific antigen-free period of 3 years. These data suggest that annual prostate specific antigen measurements are unnecessary, especially after a prostate specific antigen-free interval of 3 years. Prostate specific antigen measurements every 2 years should capture the majority of low risk patients who experience progression.

“Staging the Aging” When Considering Androgen Deprivation Therapy for Older Men With Prostate Cancer

“Staging the Aging” When Considering Androgen Deprivation Therapy for Older Men With Prostate Cancer

Patient Anxiety About Prostate Cancer Independently Predicts Early Initiation of Androgen Deprivation Therapy for Biochemical Cancer Recurrence in Older Men: A Prospective Cohort Study

Androgen deprivation therapy (ADT) is first-line therapy for patients with prostate cancer (PCA) who experience biochemical recurrence (BCR). However, the optimal timing of ADT initiation is uncertain, and earlier ADT initiation can cause toxicities that lower quality of life (QOL). We tested the hypothesis that elevated cancer anxiety leads to earlier ADT initiation for BCR in older men. We conducted a prospective cohort study of older patients with BCR of PCA (n = 67). Patients completed questionnaires at presentation and each follow-up visit until initiation of ADT. PCA-specific anxiety was measured with the Memorial Anxiety Scale for Prostate Cancer (MAX-PC). Other collected data included demographics, clinical information, and general anxiety information. Treating oncologists were surveyed about their recommendations for ADT initiation. The primary outcome was the time to ADT initiation. Univariate, multivariate logistic regression, and time-to-event analyses were conducted to evaluate whether cancer anxiety was a predictor of earlier initiation of ADT. Thirty-three percent of patients initiated ADT at the first or second clinic visit. Elevated PCA anxiety (MAX-PC > 16) was the most robust predictor in multivariate analyses of early initiation (odds ratio [OR], 9.19; P = .01). PSA also independently correlated with early initiation (OR, 1.31; P = .01). PSA did not correlate with MAX-PC. Cancer anxiety independently and robustly predicts earlier ADT initiation in older men with BCR. For older patients with PCA, earlier ADT initiation may not change life expectancy and can negatively impact QOL. PCA-specific anxiety is a potential target for a decision-making intervention in this setting.

Anesthetic Technique for Radical Prostatectomy Surgery Affects Cancer Recurrence

Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

Variance in physician attitudes toward androgen deprivation therapy initiation for biochemical cancer recurrence

15626 Background: The optimal timing for starting Androgen Deprivation Therapy (ADT) for patients with recurrent prostate cancer (PCa) remains uncertain. In 2004, the American Society of Clinical Oncology deemed the evidence insufficient to recommend early ADT initiation. Recent evidence shows a slight survival benefit to recurrent PCa patients with high risk features; however, early initiation can prematurely reduce patients’ quality of life without providing benefit. This pilot study surveys physician attitudes and practices regarding ADT initiation at a single institution. Methods: Physicians (n=20), including 7 attendings and 13 fellows, who treated biochemically- recurrent PCa patients enrolled in a companion study completed a survey about clinical experience, knowledge of recommendations, and attitudes regarding decisions to start ADT. They also rated the importance of sixteen factors potentially contributing to the decision. Results: Consistent with the ASTRO definition, forty-five percent answered, that three consecutive PSA-rising tests constitute recurrence. For patients with high risk features (Gleason &gt; 7, doubling time &lt; 10 months), 55% said ADT should be started immediately, while only 15% noted that the literature remains unresolved on this issue. For patients without high risk features, 100% would defer ADT. The two factors rated most important in determining ADT initiation timing were PSA doubling time (100%) and patient preferences (95%). Conclusions: Our preliminary data suggest that even within one institution, there is variance in physicians’ definitions of PCa recurrence and the correct treatment strategy. Despite the lack of definitive data on the benefit of early ADT initiation even for high risk patients, over 50% said such patients should start immediately. No significant financial relationships to disclose.

Cancer Fear and Mood Disturbance After Radical Prostatectomy: Consequences of Biochemical Evidence of Recurrence

Biochemical recurrence of prostate cancer often precedes any clinical sign or symptom of disease recurrence by several years. Thus, patients may have laboratory evidence of recurrence and do not know what it portends in terms of the future disease course. Little is known about the emotional consequences of biochemical recurrence. We compared cancer fear and mood disturbance in men with biochemical recurrence of prostate cancer versus those without recurrence. In addition, associations among urinary symptoms, cancer fear and mood disturbance were examined. A survey including the American Urological Association symptom index, a cancer fear measure and the Profile of Mood States was mailed to patients at a urology clinic at a tertiary care hospital in 1999. Of the sample of 270 patients with prostate cancer who underwent radical prostatectomy 126 (47%) responded to the mailed survey. A total of 45 men with biochemical prostate cancer recurrence were compared to 81 patients without recurrence. Higher urinary tract symptoms were associated with increased cancer fear and mood disturbance (each p <0.05). Biochemical cancer recurrence was not independently associated with increased cancer fear and mood disturbance. However, men with biochemical recurrence and more severe urinary tract symptoms reported the highest levels of cancer fear and mood disturbance (each p <0.01). Psychological distress was highest in men with biochemical recurrence and elevated clinical symptoms. Urinary symptoms may be an important contributor to psychological distress in patients with prostate cancer who have biochemical recurrence.