Prognostic value of neuroendocrine serum markers and PSA in irradiated patients with pN0 localized prostate cancer

BACKGROUND: The prognosis of patients with localized prostate cancer depends on clinical stage, histological grade, and pretreatment prostate-specific antigen (PSA). We evaluated the additional prognostic impact of serum levels of neuron-specific enolase (NSE) and chromograninA (CgA) after curative radiotherapy and the importance of serum PSA, analyzed 3 months after irradiation. METHODS: From 1988 to 1995, 161 patients with localized T1-4, pN0M0, prostate adenocarcinoma were treated with external radiation (66Gy, 2Gy/5 fractions per week). Frozen serum samples were assessed for CgA, NSE, and PSA before and 3 months after radiotherapy. CgA was analyzed in only 100 patients. NSE and CgA were determined by a immunometric assay. Total PSA was measured by a time-resolved fluoro-immunometric assay. RESULTS: Prior to radiotherapy CgA was elevated in 16 of 100 patients, and NSE was elevated in 33 of the 161 patients. There was no association between grade, T category or pretreatment PSA and the levels of neuroendocrine markers. Pretreatment-elevated serum NSE, but not initial CgA, identified patients with an unfavorable prognosis. A < 50% reduction of PSA 3 months after radiotherapy was associated with decreased failure-free 10 years urvival. Multivariate analysis demonstrated an increased risk of failure for patients with elevated pretreatment NSE and PSA values, T3 category, and decline of PSA less than 50% 3 months after radiotherapy. The presence of none or several risk factors (1-4) defined clearly separable groups. CONCLUSIONS: Together with T category and pretreatment serum PSA values, serum NSE values before radiotherapy and decrease of serum PSA 3 months after radiotherapy represent easily assessable prognostic parameters in patients undergoing curative radiation treatment for prostate cancer.     

Hormone-resistant prostate cancer with symptomatic pelvic tumours: patient survival and prognostic factors

OBJECTIVES: To determine the survival and investigate the prognostic significance of immunohistochemical variables and clinical factors in patients with hormone-resistant prostate cancer (HRPC) and symptomatic pelvic tumours, in whom preliminary observations indicated that survival exceeded the median 8-10 months of patients with HRPC and painful bone metastases. PATIENTS AND METHODS: Seventy-five patients with HRPC referred for palliative pelvic radiotherapy between 1980 and 1996 were identified. For all patients at least two prostate biopsies had been obtained, one before primary hormone treatment and at least one after clinical progression despite androgen deprivation (HRPC biopsy). Bone scans at the time of referral were assessed. The medical records were reviewed for clinical variables of possible prognostic significance. Histological grade was recorded, and prostate-specific antigen (PSA), androgen receptors (ARs), Ki-67 and p53 determined immunohistochemically. In 18 HRPC specimens the degree of AR amplification was analysed. RESULTS: Positive staining for ARs was high in the HRPC biopsies, although there was no association with AR amplification. Ki-67 positivity increased after the development of HRPC. The median (range) survival was 14 (1-141) months; age < 65 years was associated with increased survival. In a multivariate analysis the following variables remained independent prognostic factors for survival from the time of the HRPC biopsy: bone metastases (0-10 vs > 10 lesions, P < 0.001), low Ki-67 score (0 vs 1-3, P = 0.006) and low p53 positivity score (0 vs 1-3, P = 0.014) in the HRPC biopsy. CONCLUSIONS: The median survival of patients with HRPC and pelvic tumours requiring palliation seems to exceed that of patients with HRPC and dominating painful bone metastases by at least 4-6 months. Simple clinical (bone metastases) and immunohistochemical variables (Ki-67, p53) enable patients with particularly long survival times to be identified, and in whom palliative treatment needs to be improved.     

Implications of circulating chromogranin A in prostate cancer

OBJECTIVE: To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. MATERIAL AND METHODS: Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay. RESULTS: Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416). CONCLUSIONS: It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.     

Prostate-specific antigen levels and prognosis in patients with hormone-refractory prostate cancer treated with low-dose dexamethasone.

OBJECTIVE: The efficacy of low-dose dexamethasone (DXM) therapy in patients with hormone-refractory prostate cancer (HRPC) was evaluated. PATIENTS AND METHODS: Prostate-specific antigen (PSA) response and survival following DXM therapy were analyzed in 27 Japanese patients exhibiting HRPC. Concurrent therapies and antiandrogen withdrawal syndrome, which may affect PSA levels and palliative effects, were excluded from the study. A dose of 1.5 mg of DXM was administered, and androgen deprivation therapy was maintained during DXM therapy. A decline in PSA levels of at least 50% from baseline was considered a significant PSA response. Prognostic factors for PSA response and survival were examined by univariate and multivariate analyses. RESULTS: A significant PSA response was observed in 16 of the 27 cases (59.3%). Median survival period of patients exhibiting significant PSA response was 15.9 months and was significantly longer than that of patients demonstrating a decline in PSA of less than 50% (median 7.7 months, p < 0.0001). Effect on pain control also correlated with the significant PSA response. No meaningful prognostic factors for PSA response were detected; however, a PSA decline of greater than 50% was the prognostic factor for survival. CONCLUSION: DXM therapy remains one of the most beneficial treatment modalities in patients with HRPC.     

Circulating chromogranin a and hormone refractory prostate cancer chemotherapy

PURPOSE: Neuroendocrine differentiation is a frequent pattern in prostate adenocarcinoma. CgA seems to be a useful indicator of neuroendocrine differentiation in patients with HRPC. We evaluated the clinical interest of circulating CgA in HRPC. MATERIALS AND METHODS: Serum CgA was assessed by immunoradiometric assay in 39 patients with HRPC treated with paclitaxel and carboplatin or mitoxantrone. Baseline CgA and its variation during chemotherapy were studied. RESULTS: Increased serum CgA was observed in 45% of patients. Previous local radiotherapy and the duration of hormonal therapy were independent factors that influenced CgA. There was no correlation between CgA and prostate specific antigen. Increased serum CgA showed positive predictive significance but no prognostic value. The chemotherapy response correlated with a CgA decrease of greater than 25%. CONCLUSIONS: The current study suggests that CgA assessment facilitates patient selection by predicting the chemotherapy response and providing complementary information to follow the chemotherapy response.     

Neuroendocrine differentiation in stage D2 prostate cancers

Objectives: Chromogranin A (CgA) and neuro‐specific enolase (NSE) are gaining acceptance as markers of several types of neuroendocrine tumors and the concentration of CgA and NSE have been reported to be elevated in relation to neuroendocrine differentiation of prostate cancer. The aim of the present study was to examine the correlation between the immunohistochemical (IHC) findings and serum value for CgA and NSE in untreated stage D₂ prostate cancer patients. Methods: Immunohistochemistry was carried out using antibodies against CgA and NSE in 58 patients and, pretreatment serum CgA and NSE levels were measured by monoclonal immunoradiometric assay in 18 patients with stage D₂ prostate cancer treated by androgen ablation. We examined the relationship of the pretreatment serum level to IHC findings for CgA and NSE in prostate cancer patients to clinicopathological parameters, and prognosis. Also, we evaluated the correlation of IHC findings to serum levels for CgA and NSE. Results: There was a statistically significant correlation between CgA positivity and serum CgA level (P = 0.0421). However, there was no statistically significant correlation between NSE positivity and serum NSE level (P > 0.05). We divided stage D₂ patients into three groups according to IHC positivity of CgA and NSE. The cause‐specific survival was significantly poorer in patients with strongly positive (++) patients for independent CgA and combined CgA with NSE (P = 0.0379). Multivariate analysis of cause‐specific survivals in patients with stage D₂ prostate cancer demonstrated that strong IHC stain was considered as independent variable associated with greater risk of death (P = 0.0142). Conclusion: Neuroendocrine differentiation in stage D₂ prostate cancer has attracted considerable attention as a potentially findings prognosis. Thus, CgA had a stronger relationship between serum levels and IHC positivity in contrast to NSE, suggesting clinical usefulness as a tumor marker in predicting the extent of neuroendocrine differentiation in prostate cancer.     

Serum chromogranin-A in advanced prostate cancer

OBJECTIVE: To determine the value of serum chromogranin A (CgA), a marker of neuroendocrine differentiation, for monitoring prostate cancer: CgA levels were related to three other tumour markers, i.e. total prostate-specific antigen (tPSA), prostatic acid phosphatase (PAP), neurone-specific enolase (NSE), and to testosterone, to assess the importance of hormone withdrawal. PATIENTS AND METHODS: Serum samples (218) were obtained from 118 patients with prostate cancer, including 111 patients with advanced prostate cancer: 103 presented to our centre for systemic radionuclide therapy of painful skeletal metastases. CgA concentrations were measured using a new immunoradiometric assay (IRMA: Cis Bio International, Gif sur Yvette, France) and a threshold of 70 ng/mL was determined after receiver operating characteristic curve analysis. Testosterone was also measured with an IRMA assay; tPSA, PAP and NSE were assayed using the time-resolved amplified cryptate emission. RESULTS: Serum marker levels were high in 64% of the patients for CgA, 24% for NSE, 89% for tPSA and 81% for PAP. Patients resistant to endocrine treatments and with elevated tPSA (i.e. hormone-independent) showed increased CgA and NSE in 62% and 29%, respectively. Patients with hormone-dependent prostate cancer (i.e. with a normal tPSA level) had elevated CgA in 59% but no abnormal NSE. All patients of the latter group except one showed clinical progression of their disease. However, the mean (SD) concentrations of CgA in hormone-independent (146) or hormone-dependent (22) patients, at 185.3 (449.1) and 160.9 (293.9) ng/mL, respectively, were not statistically different (P=0.8, Mann-Whitney U-test). For 30 patients, blood samples were drawn and markers measured before and after systemic radionuclide therapy. There was a significant increase in the CgA and tPSA concentrations after treatment (P=0.0146 and 0.0025, respectively). CONCLUSIONS: In association with tPSA, serum CgA appears to be a promising marker for monitoring patients with prostate cancer.     

Neuroendocrine differentiation in carcinomas of the prostate: Do neuroendocrine serum markers reflect immunohistochemical findings?

The aim of the present study was to examine the correlation between the immunohistochemical findings and the serum markers for neuroendocrine (NE) cells in patients with carcinoma of the prostate. Preoperative serum values of chromogranin A (CgA), chromogranin B (CgB), pancreastatin (Pst), neuron-specific enolase (NSE), and prostatic specific antigen (PSA) were determined in 22 patients. The tissue specimens were obtained by a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. Immunohistochemistry was performed by using antibodies against CgA, CgB, NSE, serotonin, thyroid-stimulating hormone (TSH), and somatostatin. Tumor cells with NE differentiation were found in 91% of the cases. No patient had elevated serum values of NSE, despite the presence of NSE-positive tumor cells in 77% of the tumors. Neither did CgB in serum correlate with the immunohistochemical findings. Elevated serum values of CgA were found in 59% of patients. A positive correlation between the number of CgA-staining cells and the serum values of CgA was found, as seven out of eight patients with groups of CgA-positive tumor cells had elevated serum values of CgA. We conclude that CgA, in contrast to NSE, CgB, and Pst, seems to be a useful serum marker in predicting the extent of NE differentiation in prostatic tumors. Prostate 30:1–6, 1997 © 1997 Wiley-Liss, Inc.     

Skewing towards neuroendocrine phenotype in high grade or high stage androgen-responsive primary prostate cancer

OBJECTIVE: The prognostic influence of neuroendocrine (NE) differentiation in prostate cancer patients is not yet properly established. In a series of primary hormone-naive prostate cancers from a patient population that underwent radical prostatectomy, we wanted to determine the relationship between NE phenotype expression and Gleason sum, disease stage, and serum PSA concentration. METHODS: Chromogranin A (CgA) expression was scored and compared in 105 consecutive primary prostate cancers with their homologous preoperative tumor prostate biopsies. RESULTS: High grade or high stage prostate cancers expressed a significantly higher CgA score than low grade or localized diseases (p < 0.005). Both the CgA score of the surgical specimens and the PSA level in the serum increased linearly (p = 0.001). In the samples of many corresponding tumor biopsies no significant CgA staining was found. CONCLUSION: NE differentiation in primary untreated prostate cancer is closely associated with the major prognostic parameters of survival. This association cannot be shown by evaluating the CgA staining in tumor biopsies.     

Chemotherapy for the Treatment of Hormone-Refractory Prostate Cancer

Men with metastatic prostate cancer treated with androgen ablation therapy respond rapidly and often dramatically, with improvement in bone pain, regression of soft tissue metastases, and decreases in serum prostate-specific antigen (PSA) levels. Unfortunately, few treatment options are available to men with advanced prostate cancer in whom disease progresses after hormonal therapy. The combination of mitoxantrone with a corticosteroid is effective palliative therapy for bone pain; however, it is not associated with an improvement in overall survival. Recent studies have focused on the proteins that regulate apoptosis as a target for the treatment of hormone-refractory prostate cancer (HRPC). Agents that inhibit microtubule-associated proteins, such as estramustine, and agents known to phosphorylate Bcl-2, such as the taxanes, demonstrate high activity in HRPC. Estramustine-based regimens are commonly used for the treatment of men with HRPC. Results of phases I and II clinical trials evaluating the taxanes as single agents and combined with estramustine have demonstrated significant activity in terms of response rate, decrease in PSA level, and improvement of bone pain. Moreover, although completion of phase III trials is awaited, survival data with estramustine-taxane combinations appear promising in phase II trials.     

Prospective study of estramustine phosphate for hormone refractory prostate cancer patients following androgen deprivation therapy

INTRODUCTION: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. METHODS: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5-540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. RESULTS: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2-18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2-45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). CONCLUSIONS: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.     

Palliative treatment of bone metastases in hormone-refractory prostate cancer: effects of pamidronate on the carboxyterminal telopeptide of type-I collagen level in patients with increasing prostate-specific antigen levels

PURPOSE: Bisphosphonates have been reported to be effective in reducing bone pain and skeletal-related events associated with bone metastases in hormone-refractory prostate cancer (HRPC). However, whether bone resorption is reduced primarily by these particular drugs is difficult to evaluate because patients with HRPC are usually treated with secondary or tertiary hormonal manipulations including second-line antiandrogens, high-dose diethylstilbestrol, or low-dose dexamethasone therapies, some of which may also be effective. Thus, we assessed changes in the level of the carboxyterminal telopeptide of type-I collagen (ICTP), a bone resorption marker, before and after pamidronate administration in HRPC patients with increasing prostate-specific antigen (PSA) levels. PATIENTS AND METHODS: Twenty-one HRPC patients with bone metastases and increasing PSA levels were intravenously treated with pamidronate at a dose of 30 mg either every 2 or every 4 weeks. Pamidronate administration was started immediately after confirmation of three consecutive increases in the PSA level. RESULTS: In 14 patients (67%), the ICTP levels decreased after the administration of pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels were lower than those recorded for 6 months or longer before the start of pamidronate administration. The characteristics of the responders were compared with those of the non-responders. CONCLUSION: In 67% of the HRPC patients with increasing PSA levels, pamidronate reduced the accelerated turnover of bone metabolism caused by metastases of prostate cancer.     

Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group

OBJECTIVES: To compare toxicity, subjective response rate, time to subjective progression and overall survival in patients with painful bone metastases of hormone-resistant prostate cancer (HRPC) treated with a single intravenous injection of 150MBq (4mCi) Strontium(89) Chloride (S) or palliative local field radiotherapy (R) with the usual radiotherapy regimen used at each centre. The costs of both treatments were also assessed. PATIENTS AND METHODS: 101 patients were randomized to S and 102 to R. Time to event endpoints were compared with the Logrank test and Kaplan-Meier curves, in the intent-to-treat population (2-sided alpha=0.05). RESULTS: Baseline characteristics of both groups were comparable. There was a borderline statistically significant difference in overall survival in favour of the local field radiotherapy (R: 11 months; S: 7.2 months; p=0.0457). There was no difference in progression-free survival or time to progression. Subjective response was seen in 34.7% in the S-arm and in 33.3% in the R-arm. A biochemical response was observed in 10% and 13% of the R- and S-groups, respectively. There was no difference in treatment toxicity between the two groups. CONCLUSION: In symptomatic HRPC, pain treatment with local field radiotherapy is associated with a better overall survival compared to Strontium(89). The lower costs of local field radiotherapy also favour the use of this treatment in patients with HRPC. The reason for the apparent survival benefit of localised radiation treatment is not clear.     

Variation of chromogranin A serum levels after radical retropubic prostatectomy for prostate adenocarcinoma

This study evaluated perioperative and postoperative variations in serum CgA levels induced by radical retropubic prostatectomy (RRP) and their relationship with serum PSA levels in prostate cancer patients. Thirty consecutive patients with clinically localized adenocarcinoma of the prostate undergoing RRP were prospectively analyzed. Serum levels of CgA and total PSA were analyzed in each case preoperatively (time 0), at removal of the prostate (time 1), 1 h after the end of RRP (time 2) and then at regular postoperative intervals till 12 weeks (time 14). During the postoperative period no adjuvant therapies were performed and none of the 30 cases showed biochemical (PSA > 0.2 ng/mL) and/or clinical progression. Mean preoperative serum levels of CgA were 57 +/- 14 ng/mL. Immediately after the surgical removal of the prostate gland (time 1), in all 30 cases there was a significant (time 0-time 1: p = .001) increase in serum PSA, but a nonsignificant modification in serum CgA levels (60 +/- 15 ng/mL). After time 1, serum PSA levels progressively decreased to below the detection limit of 0.2 ng/mL. On the contrary, at time 2, serum CgA levels were postoperatively increased (time 2 = 145 +/- 47) and they remained significantly higher than preoperative values (time 0) till the 21-day postoperative interval (time 11). Moreover, at the last control (time 14) mean and median CgA levels were very similar to those shown preoperatively (time 14: 58 +/- 18 ng/mL). In patients with untreated clinically localized adenocarcinoma of the prostate submitted to RRP, surgical and postoperative stress, more than surgical manipulation of the prostate gland, could produce a significant increase in serum CgA levels maintained for a longer period when compared to the increase in serum PSA levels.     

Serum alkaline phosphatase flare in prostate cancer accompanied by bone metastases and treated with hormonal therapy. TEKK Study Group

To clarify the roles of alkaline phosphatase (ALP) flare in prostate cancer accompanied by bone metastases and treated with hormonal therapy, we evaluated the clinicopathological character, treatment efficacy and outcome for patients with and without ALP flare. We evaluated 60 patients with newly diagnosed prostate cancer accompanied by bone metastases and treated with hormonal therapy, whose response in terms of serum prostate specific antigen (PSA) levels showed a partial response (PR) or better response. The patients were classified into two groups, an ALP flare group (13 cases) and a non-ALP flare group (47 cases). The former showed serum ALP elevation of more than double, and the latter less than double that of pretreatment levels following hormonal therapy. Patient characteristics, PSA response and outcome were compared between the two groups. Extent of disease (EOD) as grade of bone metastasis was significantly higher in the ALP flare group than in the non-flare group (p = 0.0352). Pre-treatment serum PSA levels were also significantly higher in the ALP flare group (p = 0.0010). However, there were no significant differences in pretreatment serum ALP levels. Serum PSA levels were normalized in 37 of the 47 patients (78.7%) in the non-ALP flare group compared with 6 of the 13 (46.2%) in the ALP flare group (p = 0.0211). Moreover, the period until biochemical failure was significantly shorter for the ALP flare than the non-flare group (p = 0.0027). These results suggest that prostate cancer patients with bone metastases in whom ALP flare is observed in response to hormonal therapy tend to have more extensive bone metastases, high pretreatment PSA levels, to be resistant to PSA normalization and more likely to experience biochemical failure.     

Expression of p21 cell cycle protein is an independent predictor of response to salvage radiotherapy after radical prostatectomy

BACKGROUND: To assess whether the expression of p21, p27, and p53 could predict biochemical failure in prostate cancer patients treated with neoadjuvant androgen deprivation prior to salvage radiotherapy for a rising post-radical prostatectomy (RP) prostate-specific antigen (PSA). METHODS: The expression of p21, p27, and p53 was determined by immunohistochemistry in a cohort of 74 formalin-fixed paraffin-embedded prostate cancer samples obtained from RP. Expression of these markers was then correlated with clinicopathological parameters and biochemical failure-free survival after salvage radiotherapy. RESULTS: Expression of p21, p27, and p53 was observed in 20%, 69%, and 74% of prostate cancer specimens, respectively. Overexpression of p21 correlated with a higher Gleason score (>7) (P = 0.024). Of the three markers, only p21 expression was correlated with PSA failure after radiotherapy (P = 0.034). In multivariate analysis, both positive p21 (P = 0.004) and pre-radiation serum PSA > 1 ng/ml (P < 0.0001) were independent predictors of biochemical failure after salvage radiotherapy. Patients with p21- tumors and a serum PSA level < or = 1 ng/ml before salvage radiotherapy had a biochemical failure-free survival at 5 years of 83%, compared to 16% at 5 years for those patients with either p21+ tumor or a PSA > 1 ng/ml. Patients with both p21+ and a PSA level > 1 ng/ml had a much lower biochemical failure-free survival rate of 25% at only 18 months (P < 0.0001). CONCLUSIONS: The expression of p21 in prostatectomy specimens could help predict the likelihood of response to salvage radiotherapy, particularly in patients treated before PSA reaches 1 ng/ml.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.