Disease In Prostate Cancer Patients Research Articles

Efficacy of ferumoxytol as a lymphatic contrast agent in prostate cancer.

186 Background: Ferumoxytol (Feraheme) is a ferromagnetic nanoparticle with lymphotrophic biokinetics, delivered to lymph nodes by normal macrophages. MRI suppresses normal lymph nodes containing Feraheme. Objective is to validate safety and efficacy in finding lymph node positivity in prostate cancer (PCa). Methods: Nonrandomized prospective evaluation of 178 consecutive PCa patients (pts) at high risk for lymph node spread enrolled 2/13-3/15. All received IV Feraheme. 177 received 6/mg/kg over 20 min. One pt received 3 mg/kg infusion. T2 MEDIC and T2* sequence imaging of abdomen and pelvis, given 24 hours later. Images reviewed by 2 board certified radiologists with same interpretations, blinded to clinical and histo-path info (pre-MRI TNM stage/PSA/Gleason). Nodes were deemed abnormal if they did not suppress after Feraheme infusion (group 1, 94 patients). Nodes were deemed suspicious if suppressed and met usual size criteria with high signal intensity on DWI and decreased ADC map values and morphologic features (group 2, 84 pts). 83 group 1 pts had CT biopsies (77 pelvis, 6 retroperitoneum);11 pts had open PLND. 382 lymph nodes sampled. 76 group 2 patients had CT biopsies (73 pelvis, 3 retroperitoneum); 9 pts had open PLND. 340 lymph nodes sampled. Rad-path correlation was performed. Nodes were stained; reviewed by a single pathologist with no knowledge of MRI findings. Histo-path results for each node were cataloged for later MRI comparison. Results: 90 group 1 pts (96%) proved metastatic PCa; 4 pts (4%) were normal. 68 group 1 pts (77%) had malignant lymph nodes not meeting usual imaging criteria. 39 group 2 pts (47%) showed metastatic PCa; 46 pts (53%) were normal. One group 2 pt had an allergic reaction with hives; infusion ceased at 3mg/kg; pt treated to full resolution with 50 mg IV Benadryl. Conclusions: Feraheme can evaluate lymphatic dissemination of metastatic disease in PCa patients, with a lower limit of resolution of focal lymph node metastases of 2-3 mm. Better resolution gives implications for therapeutic radiation planning of newly diagnosed or recurrent/metastatic PCa. Toxicity was very acceptable at 6mg/kg. Feraheme may play a significant role as a lymphatic contrast agent in the early dissemination of lymphatic metastatic disease.

Biochemical Recurrence of Prostate Cancer: Initial Results with [18F]PSMA-1007 PET/CT.

Biochemical recurrence (BCR) is a concern for prostate cancer patients after local treatment. 68Ga-labeled prostate-specific membrane antigen (PSMA) ligands have significantly improved prostate cancer imaging. However, several 18F-labeled ligands that were developed as fluorinated tracers might present advantages. In this study, we analyzed the potential of 18F-PSMA-1007 in patients with BCR. Methods: Twelve patients with BCR after local treatment underwent PET/CT scans 1 and 3 h after injection of 18F-PSMA-1007. Results:18F-PSMA-1007 PET/CT detected lesions in 9 of 12 patients (75%). A significant difference was observed when comparing the tracer uptake in 18F-PSMA-1007-positive lesions 1 and 3 h after injection (median SUVmax, 7.00 vs. 11.34; P < 0.001; n = 76). Forty-four (88%) of 50 18F-PSMA-1007-positive lymph nodes had a short-axis diameter of less than 8 mm. Conclusion: In this pilot study, 18F-PSMA-1007 PET/CT presented high potential for localization of recurrent disease in prostate cancer patients with BCR.

816P - 68Ga-PSMA-PET/CT as a changing practice tool in biochemically recurrent prostate cancer

Background: PSMA-PET/CT have demonstrated interesting results in the detection of loco-regional and distant disease in prostate cancer patients with biochemical relapse. Even with low levels of PSA, PSMA imaging is able to identify metastatic lesions, being a possible tool for tailoring treatment decisions. This study aims to describe the use of PSMA-PET/CT in the daily practice and its clinical impact in the management of prostate cancer patients who have rising PSA after curative treatment. Methods: We performed a retrospective analysis in 29 localized prostate cancer patients of three private Brazilian cancer institutions who underwent PSMA-PET/CT for rising PSA after treatment with curative intent. The clinical impact of PSMA-PET/CT was evaluated by whether the assistant physician changed or not the treatment strategy based solely on PSMA results. In addition, modifications related to local (salvage radiotherapy [SRT], salvage lymphadenectomy [SL]) and systemic (antiandrogen deprivation therapy [ADT], chemotherapy [chemo]) treatment were described. Results: In total, 29 patients were enrolled. Twenty-seven (93%) had undergone radical prostatectomy, and 2 (7%) radiotherapy as the local curative treatment. Sixteen cases (55%) had not received any radiotherapy previously. The mean Gleason score, PSA level and PSADT at time of the examination were 8, 4.2 (0,05-41) ng/ml and 4.4 (0.4-27) months, respectively. PSMA-PET/CT detected at least one suspicious lesion for prostate cancer in 21/29 (58%) patients. Overall, 15/29 (51%) patients had their treatment strategy changed due to results in PSMA imaging. In only 3/29 (10%) the modifications were related exclusively to systemic protocols (1 avoided ADT, 1 added ADT and, 1 added chemo). Whereas in the 12/29 (41%) remaining cases, treatment strategy change involved local treatment. Of these 12 with a local treatment change, 7 added (6 SL, 1 SRT) and 5 avoided (5 SRT) local therapies. Conclusions: Half of the patients with biochemical relapse that underwent PSMA-PET/CT had their treatment protocol changed, most changes related to local treatment. Although the role of PSMA imaging is not clearly defined, PSMA-PET/CT has been used as a practice changing tool in the daily practice. Legal entity responsible for the study: Instituto COI Funding: None Disclosure: All authors have declared no conflicts of interest.

The study and comparison of the severity of coping strategies and defense mechanisms in prostate cancer patients, healthy individuals and patients with similar localization oncology

This project deals with the problem of emotional response to their disease in prostate cancer patients compared with healthy people and patients with similar localization of oncology diseases. As a result, it was found that in patients with prostate cancer pronounced such defense mechanisms as repression, denial and reaction formation, which may lead to psychosomatic disease. The coping strategies of the system in patients with prostate cancer is most pronounced, such a mechanism as a “distancing”. The results may contribute to the creation of a specific psychological rehabilitation for this group of patients the program.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Oligometastatic bone disease in prostate cancer patients treated on the TROG 03.04 RADAR trial

BackgroundIt remains unclear whether eradication of oligometastases by stereotactic body radiation therapy or other means will result in cure or prolongation of survival in some cases, or merely provide palliation. We address this issue with prospectively collected progression and treatment data from the TROG 03.04 RADAR randomised controlled trial for men with locally advanced prostate cancer (PC). MethodsThree Fine and Gray competing risk survival models with time-dependent covariates were used to determine whether metastatic progression status at first diagnosis of bony metastases, i.e. number of bony sites involved and presence of prior or simultaneous other sites of progression, impacts on prostate cancer-specific mortality (PCSM) when adjusted for baseline prognostic factors and allocated primary treatment. ResultsBetween 2003 and 2014, 176 of the 1071 subjects developed bone metastases, 152 developed other sites of progression and 91 died of PC. All subjects received secondary treatment using androgen suppression but none received extirpative treatments. The three models found evidence: 1 – of a clear prognostic gradient according to number of bony metastatic sites; 2 – that other sites of progression contributed to PCSM to a lesser extent than bone progression; and 3 – that further bony metastatic progression in men with up to 3 bony metastases had a major impact on PCSM. ConclusionRandomised trials are essential to determine the value of extirpative treatment for oligometastatic bony metastases due to PC.

(11)C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series.

To evaluate (11)C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing (11)C-choline PET/CT during BCR. We retrospectively analysed 9,632 (11)C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2ng/mL after RP or PSA >2ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. Overall, 52.8% of the (11)C-choline PET/CT scans (2,337/4,426) and 54.8% of the patients (1,755/3,203) were positive. In 29.4% of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1ng/mL at the time of the scan (range 0.2-50ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7%, with an incidence of distant findings of 19.2% and an incidence of oligometastatic disease (one to three lesions) of 37.7%. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive (11)C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16ng/mL was the optimal cut-off value. In patients with a PSA value <1.16ng/mL, 26.8% of 1,426 (11)C-choline PET/CT scans were positive, with oligometastatic disease in 84.7% of positive scans. In a large cohort of patients, the feasibility of (11)C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.

Abstract 2229: CD117 expression and activation in prostate cancer progression

Abstract We have demonstrated that CD117/c-kit expression on circulating tumor cells and in primary tumors correlates with advanced disease in prostate cancer patients. In addition, the ligand for CD117, stem cell factor (SCF) is increased in high-grade prostate cancer patients. To examine the effects of CD117 activation and expression on prostate cancer progression, we sorted CD117 positive and negative RM1 murine prostate cancer cells and LNCaP-C4-2 human prostate cancer cells. Sorted cells were then examined for tumorigenicity, proliferation, cell signaling, cell migration, angiogenesis and epithelial-mesenchymal transition. A xenograft model demonstrated that CD117 positive LNCaP-C4-2 tumors generate larger tumors characterized by increased vascularization and proliferation. In vitro, SCF induced CD117 activation results in altered cell signaling, migration and epithelial-to-mesenchymal transition. In addition, in vivo imaging of tumor growth demonstrated changes in tumor cell organization between CD117 positive and negative cell populations. In summary, CD117 expression and activation enhances prostate cancer progression. Citation Format: Bethany Kerr. CD117 expression and activation in prostate cancer progression. [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 2229. doi:10.1158/1538-7445.AM2015-2229

Abstract 5065: Interleukin-1β secreted into the bone metastatic niche by androgen receptor-negative prostate cancer cells enables skeletal metastasis

Abstract Advanced prostate cancer (PCa) frequently leads to bone metastasis, a major cause of morbidity and mortality. Limited knowledge of the molecular interactions underpinning the behavior of cancer cells in the bone microenvironment has stymied the development of curative therapies. Signaling between cancer cells and stroma likely plays a crucial role in dictating the fate of disseminated tumor cells (DTCs), and its disruption could interfere with the supportive role of the metastatic niche and thus hamper tumor growth. We previously identified interleukin-1β (IL-1β) as a major mediator of the bone-metastatic behavior of human prostate cancer cells inoculated into the left cardiac ventricle of SCID mice. Here, we show not only that pharmacologic disruption of IL-1β signaling using the IL-1 receptor (IL-1R) antagonist anakinra diminishes the metastatic potential of PCa cells in vivo, but also that IL-1β secreted by PCa cells can prompt bone stromal cells to acquire a carcinoma-associated fibroblast (CAF) phenotype. Emphasizing the role of the stroma, we demonstrate that SCID mice null for IL-1R display diminished formation of bone metastases relative to wild-type when inoculated with highly metastatic IL-1β-expressing PCa cells. In this same model we find that IL-1β supports early survival of DTCs in the bone. Interestingly, while the aggressively-metastatic androgen receptor (AR)-negative PC3-ML cell line expresss high levels of IL-1β, the numerous AR(+) PCa cell lines we examined each lack IL-1β expression. This was recapitulated in human tissue specimens of PCa bone metastases examined by a combination of Laser Capture Microdissection and qPCR. In these lesions, a relevant fraction of PCa cells lack AR transcript and express IL-1β, whereas AR(+) cells were uniformly negative for this cytokine. As AR(+) PCa cells are consistently non-metastatic in our pre-clinical model, we speculated that IL-1β-mediated induction of CAFs in the bone may enable growth of AR(+) PCa cells that would otherwise be unable to initiate a metastatic niche. To test this hypothesis, we co-inoculated PC3-ML and AR(+) PCa cells and evaluated their metastatic abilities using two-color labeling in both multispectral microscopy and bioluminescence imaging. We found that the presence of AR(-), IL-1β-expressing cells allowed AR(+) PCa cells both to colonize the bone and persist in macroscopic mixed tumors in the long term. Our study thus conclusively confirms the existence of AR(-) PCa cells in skeletal metastases, describes a negative correlation between AR and IL-1β expression, and implicates this cytokine in a form of metastatic cooperation between phenotypically distinct cancer cells. These discoveries may be exploited therapeutically to alter the microenvironment of the metastatic niche, with the aim to impair establishment and progression of bone metastatic disease in PCa patients. Citation Format: Kristina S. Shahriari, Fei Shen, QingXin Liu, Danielle L. Jernigan, Ramanpreet Kaur, Alessandro Fatatis. Interleukin-1β secreted into the bone metastatic niche by androgen receptor-negative prostate cancer cells enables skeletal metastasis. [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 5065. doi:10.1158/1538-7445.AM2015-5065

457 The natural course of disease in prostate cancer patients with lymph node involvement after extended pelvic lymphadenectomy and radical prostatectomy

457 The natural course of disease in prostate cancer patients with lymph node involvement after extended pelvic lymphadenectomy and radical prostatectomy

Abstract B61: Paving the way to Personalized Medicine: Diagnosis, prevention and treatment of early stage bone metastatic disease in prostate cancer patients with Theragnostic Radiopharmaceuticals.

Abstract A major advantage of radionuclides is that they emit radiation of different radiobiological effectiveness and range of action. This presentation will introduce a relatively novel paradigm that involves specific individual radionuclides or radionuclide pairs that have emissions that allow pre-therapy low-dose imaging plus higher-dose therapy in the same patient. We have made an attempt to sort out and organize a number of such theragnostic radionuclides and radionuclide pairs that may potentially bring us closer to the age-long dream of personalized medicine for performing tailored low-dose molecular imaging (SPECT/CT or PET/CT) to provide the necessary pre-therapy information on biodistribution, dosimetry, the dose limiting critical organ or tissue, and the maximum tolerated dose (MTD), etc. If the imaging results then warrant it, it would be possible to perform dose ranging studies and higher-dose targeted molecular therapy in in the same patient with the same radiopharmaceutical. Tin-117m (T1/2 14.0 d; γ 159 keV, 86%) is an ideal radionuclide for the development of theragnostic radiopharmaceuticals. In contrast to most other therapeutic beta emitters, Sn-117m decays via isomeric transition with the emission of monoenergetic conversion electrons (127, 129, and 152 keV; abundance 65, 12, and 26% respectively). These emissions have short discrete ranges of between 0.22 and 0.29 mm in tissue and they deposit an intense radiation dose only within this short range in the the selectively targeted area and causing much reduced dose to radiation sensitive bone marrow and other normal organs. Moreover, its 159 keV γ-photon is perfect for pre-therapy imaging in the same patient. We have shown Sn-117m to be effective for therapy of cancer and other inflammatory conditions (e.g., atherosclerotic disease). The results of the Phase II clinical trial of tin-117m DTPA for metastaic bone pain palliation (using reactor-produced tin-117m, with specific activity ranging between 8-20 Ci/g of tin) will be presented. NCA (no-carrier-added) tin-117m is also being developed and tested for the prevention/therapy of early stage bone metastases in prostate cancer patients and for use in radioimmunotherapy. A phase II/III clinical trial for the imaging and treatment of bone metastases in prostate cancer patients is in the planning stage for 2013. A brief description of the recently developed new or modified methods at BNL for the production and radiochemistry of a number of other potential theragnostic radionuclides, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer therapy will be provided. Work at BNL supported by the U.S. Department of Energy under Contract # DE-AC02-98CH10886. Citation Format: Suresh C. Srivastava. Paving the way to personalized medicine: Diagnosis, prevention, and treatment of early-stage bone metastatic disease in prostate cancer patients with theranostic radiopharmaceuticals. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B61. Note: This abstract was not presented at the conference.

756 Bilaterally positive biopsy cores are associated with non-organ confined disease in prostate cancer patients eligible for active surveillance

756 Bilaterally positive biopsy cores are associated with non-organ confined disease in prostate cancer patients eligible for active surveillance

The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition

BackgroundAberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3.ResultsThe WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues.ConclusionThese data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.

100 Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy

100 Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy

Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy

Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy

Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy

Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy

Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis

Hormone refractory metastatic prostate cancer remains an incurable disease. We found that high expression levels of the chemokine receptor CXCR4 correlated with the presence of metastatic disease in prostate cancer patients. Positive staining for CXCL12, the ligand for CXCR4, was mainly present in the tumor-associated blood vessels and basal cell hyperplasia. Subcutaneous xenografts of PC3 and 22Rv1 prostate tumors that overexpressed CXCR4 in NOD/SCID mice were two- to threefold larger in volume and weight vs. controls. Moreover, blood vessel density, functionality, invasiveness of tumors into the surrounding tissues, and metastasis to the lymph node and lung were significantly increased in these tumors. Neutralizing the interactions of CXCL12/CXCR4 in vivo with CXCR4 specific antibodies inhibited the CXCR4-dependent tumor growth and vascularization. In vitro, CXCL12 induced the proliferation and VEGF secretion but not migration of PC3 and 22Rv1 cells overexpressing CXCR4. Similar effects of CXCR4 overexpression on tumor growth in vivo were also noted in two breast cancer lines, suggesting that the observed effect of CXCR4 is not unique to prostate tumor cells. Thus high levels of the chemokine receptor CXCR4 induce a more aggressive phenotype in prostate cancer cells and identify CXCR4 as a potential therapeutic target in advanced cases of metastatic prostate cancer.

Clinical approaches to osseous metastases in prostate cancer.

Prostate cancer is unique among solid tumors in its proclivity to metastasize primarily to bone. Osseous metastases pose a formidable health threat to patients with metastatic disease, putting them at risk for pain, marrow crowding, fracture, and other sequelae. Treatments directed against bone disease have the potential both to palliate pain and to increase survival. A number of agents exist that have the potential to palliate the effects of osseous metastases and should be routinely applied in the clinical care of the patient with advanced prostate cancer. These include hormones, bone-seeking radiopharmaceuticals, chemotherapy, and bisphosphonates. Strategies under investigation aim to eradicate bone disease, and not merely palliate symptoms. These approaches combine those listed above with tumor-directed targeting of osseous disease and manipulation of the biology that underlies the cancer's relationship to bone.

Factores predictivos de enfermedad localmente avanzada en pacientes con cáncer de próstata tratados con hormonoterapia neoadyuvante y prostatectomía radical

AimTo analyze the predictors of local adverse pathological findings (positive surgical margins and seminal involvement) in prostate cancer patients treated with neoadjuvant hormonetherapy and radical prostatectomy Patients And MethodsWe studied seventy-eight patients treated with neoadjuvant androgen blockade prior to radical prostatectomy between 1995 and 1998. Age, PSA, prostate volume determined by transrectal ultrasound and/or magnetic resonance imaging, clinical stage, Gleason score, duration of blockade, pathological stage and tumoral volume were analyzed Results34.6% of patients (27/78) had adverse pathology (odds: 0.53). No significant differences were found in age, PSA, prostate volume, duration of blockade and Gleason score between organ-confined and locally advanced patients. Differences were found in tumor volume (p = 0.0001) but this was not different in order to positive or negative digital rectal examination (p = 0.5334). The efficacy for predicting pathological adverse findings was represented by ROC curves (PSA: 0.628, clinical stage: 0.612 and Gleason score: 0.545). Predictive table of extracapsular disease for different PSA levels, clinical stage and Gleason score were developed. No variable predicted positive margins in logistic regression model ConclusionsClinical variables do not predict locally advanced disease in prostate cancer patients treated with neoadjuvant androgen blockade. This is associated with higher tumor volumes. The probability of positive margins or seminal involvement increases with PSA level and Gleason score

Evaluation of prostate cancer patients receiving multiple staging tests, including ProstaScint scintiscans.

Multiple serum tests were performed on archival samples from patients who participated in trials to assess the ProstaScint scan staging ability. Traditional statistical analysis as well as artificial neural network (ANN) analysis were employed to evaluate individual patients and the group as a whole. The results were evaluated so that each factor was tested for prognostic value. Data obtained from serum tests, bone scans, and ProstaScint scans were evaluated by traditional statistical methods and ANN to determine the individual value in clinical staging of prostate cancer. Two hundred seventy-five patients (180 postprostatectomy, 95 intact prostate) with prostate cancer (14 with distant metastases) were available for analysis. Data available included: clinical state (remission or progression), most recent clinical TNM stage, bone scan, and ProstaScint scan. Serum was tested for prostate-specific membrane antigen(PSMA), prostate-specific antigen(PSA), free PSA (fPSA), and complexed PSA (cPSA). Additional calculations included percent free PSA, and percent complexed PSA. Spearman individual statistical assessment for traditional group evaluation revealed no significant factors for T-stage. The free PSA and complex PSA had a significant association with node (N)-status. The distant metastases (M) stage correlated well with the bone scan and clinical stage. ANN analysis revealed no significant T-stage factors. N-stage factors showed a 95% sensitivity and 49% specificity. These factors included the presence or absence of a prostate, PSA serum levels, bone scan, and ProstaScint scans as major associated indicators. ANN analysis of the important variables for M-stage included ProstaScint scan score, and PSA levels (total, percent complexed, percent free, and fPSA). These factors were associated with a 95% sensitivity and 15% specificity level. Two hundred seventy-five patients receiving treatment for prostate cancer were evaluated by ANN and traditional statistical analysis for factors related to stage of disease. ANN revealed that PSA levels, determined by a variety of ways, ProstaScint scan, and bone scan, were significant variables that had prognostic value in determining the likelihood of nodal disease, or distant disease in prostate cancer patients.