Predictors of improved outcome for patients with localized prostate cancer treated with neoadjuvant androgen ablation therapy and three-dimensional conformal radiotherapy

PURPOSE: To identify prognostic variables that predict for improved biochemical and local control outcome in patients with localized prostatic cancer treated with neoadjuvant androgen deprivation (NAAD) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: Between 1989 and 1995, 213 patients with localized prostate cancer were treated with a 3-month course of NAAD that consisted of leuprolide acetate and flutamide before 3D-CRT. The purpose of NAAD in these patients was to reduce the preradiotherapy target volume so as to decrease the dose delivered to adjacent normal tissues and thereby minimize the risk of morbidity from high-dose radiotherapy. The median pretreatment prostate-specific antigen (PSA) level was 15.3 ng/mL (range, 1 to 560 ng/mL). The median 3D-CRT dose was 75.6 Gy (range, 64.8 to 81 Gy), and the median follow-up time was 3 years (range, 1 to 7 years). RESULTS: The significant predictors for improved outcome as identified in a multivariate analysis included pretreatment PSA level < or = 10.0 ng/mL(P < .00), NAAD-induced preradiotherapy PSA nadir < or = 0.5 ng/mL (P < .001), and clinical stage < or = T2c (P < .04). The 5-year PSA relapse-free survival rates were 93%, 60%, and 40% for patients with pretreatment PSA levels < or = 10 ng/mL, 10 to 20 ng/mL, and greater than 20 ng/mL, respectively (P < .001). Patients with preradiotherapy nadir levels < or = 0.5 ng/mL after 3 months of NAAD experienced a 5-year PSA relapse-free survival rate of 74%, as compared with 40% for patients with higher nadir levels (P < .001). The incidence of a positive biopsy among 34 patients pretreated with androgen ablation was 12%, as compared with 39% for 117 patients treated with 3D-CRT alone who underwent a biopsy (P < .001). CONCLUSION: For patients treated with NAAD and high-dose 3D-CRT, pretreatment PSA, preradiotherapy PSA nadir response, and clinical stage are important predictors of biochemical outcome. Patients with NAAD-induced PSA nadir levels greater than 0.5 ng/mL before radiotherapy are more likely to develop biochemical failure and may benefit from more aggressive therapies.     

Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate

OBJECTIVES: Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide. METHODS: Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values. RESULTS: The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). CONCLUSIONS: Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed.     

Chronic urticaria associated with aseptic meningitis: an atypical urticarial vasculitis?

OBJECTIVE: This study is based on promising results using the ratio of free/ total (F/T) prostatic-specific antigen (PSA) for discrimination between benign prostatic hypertrophy and prostate cancer. We tried to determine the value of F/T PSA in different clinical situations at a certain time point during follow-up of luteinizing-hormone-releasing hormone (LH-RH) agonist treatment and to correlate it to T-PSA. PATIENTS AND METHODS: 182 patients followed-up for different periods in the last 3 years were routinely monitored for serum T-PSA. During the last 11 months, F-PSA was also measured together with T-PSA, and the ratio of F/T PSA was calculated. In 26 patients, the ratio of F/T PSA was monitored sequentially in several samples. RESULTS: Although 5 patterns of clinical response to LH-RH agonists were identified according to previous T-PSA, the F/T ratio could significantly (p < 0.05) discriminate between patients responding to treatment in contrast to patients escaping, fluctuating or not responding to hormonal ablation. Those patients responding to hormones showed a higher F/T PSA ratio (36.5 +/- 33.1%) compared to the nonresponding group (12.0 +/- 10.1%). CONCLUSIONS: During individual follow-ups, the pattern of response to LH-RH treatment is reflected by the F/T PSA ratio: while successful treatment causes an F/T PSA increase, relapse is accompanied by a decrease in this ratio. However, the changes in the F/T PSA ratio did not precede the indicative changes in T-PSA. It seems that increased values of F/T PSA ratios are intrinsic features of 'benign' prostatic disease, and the molecular events resulting in different PSA molecules in various clinical situations have to be elucidated.     

Contrasting effects of an aminobisphosphonate, a potent inhibitor of bone resorption, on lipopolysaccharide-induced production of interleukin-1 and tumour necrosis factor alpha in mice

PURPOSE: To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence. METHODS AND MATERIALS: Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml. RESULTS: At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure. CONCLUSION: This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.     

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma

BACKGROUND: The authors report observed 10-year brachytherapy results in the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. METHODS: One hundred and fifty-two consecutive patients with T1-T3, low to high Gleason grade, prostate carcinoma were treated between January 1987 and June 1988 at Northwest Hospital in Seattle, Washington. Their median age was 70 years (range, 53-92 years). Of these 152 patients, 98 (64%) received an iodine-125 implant alone (Group 1), and the remaining 54 patients (36%), who were judged to have a higher risk of extraprostatic extension, also were treated with 45 gray (Gy) of external beam irradiation to the pelvis (Group 2). No patient underwent lymph node sampling, and none received androgen ablation therapy. Multivariate regression and the Mann-Whitney rank sum test were used for statistical analysis. Preoperative patient data with associated success or failure outcomes at 10 years after treatment were used for training and validating a back-propagation neural network prediction program. RESULTS: The average preoperative prostate specific antigen (PSA) value, clinical stage, and Gleason grade were 11.0 ng/mL, T2, and 5, respectively. The median posttreatment follow-up was 119 months (range, 3-134 months). Overall survival 10 years after treatment was 65%. At last follow-up only 3 of the 152 patients (2%) had died of prostate carcinoma. Ninety-seven patients (64%) remained clinically and biochemically free of disease at 10 years of follow-up and had an average PSA value of 0.18 ng/mL (range, 0.01-0.5 ng/mL). In these patients a period of 42 months was required to reach the average PSA (0.5 ng/mL). The median to last PSA follow-up was 95 months (range, 3-134 months). Postoperative needle biopsies were negative in 56% of patients, positive in 15% of patients, and not available in 29% of patients. Only 6% of patients developed bone metastasis. At 10 years there was no statistically significant difference in treatment outcome between patients who received iodine-125 alone, and those who received iodine-125 with 45-Gy external beam irradiation (P = 0.08). Nevertheless, in these two groups preoperative PSA, stage, and Gleason grade were significantly different (P < 0.01). In the artificial neural network analysis, pretreatment serum PSA was the most accurate predictor of disease-free survival. CONCLUSIONS: Percutaneous prostate brachytherapy is a valid and efficient option for treating patients with clinically organ-confined, low to high Gleason grade, prostate carcinoma. Observed 10-year follow-up documents serum PSA levels superior to those reported in several published external beam irradiation series, and comparable to those published in a number of published radical prostatectomy series.     

Influence of the phosphatidylethanolamine (PE) and bovine serum origins on anti-PE antibody detection by ELISA

The long-term results of external irradiation in locally advanced prostate cancer are poor: relapses are local or distant from infra-clinical disease present at diagnosis. Three clinical randomized trials have shown that hormonotherapy with LH-RH analogue with or without antiandrogen has improved: disease-free survival, local recurrence-free survival and metastasis-free survival (P < 0.001). The EORTC trial 22863 has shown a significant improvement of the overall survival (P = 0.001), with an LH-RH analogue (goserilin acetate, Zoladex) was administered the first day of irradiation and then every 4 weeks for 3 years; for the RTOG trial 85-31 the same LH-RH analogue was administered during the last week of irradiation and given until relapse increases survival of patients with poor differentiated tumours with a Gleason score ranging from 8 to 10 (P = 0.03). Adjuvant hormonal treatment with an LH-RH analogue is recommended, but the optimal duration of the treatment remains unclear.     

Is prostate specific antigen density an important prognostic indicator for patients with prostate cancer treated with external beam therapy?

The purpose of this study was to determine if prostate specific antigen density (PSAD) is a predictor of outcome following external beam radiotherapy for prostate cancer, and to compare it with other prognostic factors. Between January 1990 and December 1993, 205 patients with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation, with no prior or adjuvant hormonal therapy. All patients had pre- and post-treatment serum prostate specific antigen (PSA) evaluation. They were followed up for at least 24 months. PSAD was defined as the ratio of pre-treatment serum PSA to the prostate volume, as determined from CT treatment planning scans. Prostate volumes were calculated using the prostate ellipse formula. Median PSA density was 0.37, with a range 0.01-6.7. Biochemical failure was defined as three consecutive rises in serum PSA, regardless of the magnitude of elevation. 4-year biochemical disease-free survival (BDFS) for patients with PSAD < or = 0.3 was 60%, compared with 22% for patients with PSAD > 0.3 (p = < 0.001). In a multivariate analysis, pre-treatment PSA (p = < 0.001), Gleason score (p = 0.002), and stage (p = 0.03) were independent predictors of BDFS, while PSAD was not an important prognosticator (p = 0.62). Pre-treatment serum PSA is the most important prognosticator of BDFS, following external beam radiotherapy, for patients with prostate cancer. PSA density did not predict treatment outcome.     

Stage T1-2 prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy

PURPOSE: Prostate-specific antigen (PSA) is extensively used in case selection and outcome evaluation after treatment of clinically localized prostate cancer. Careful case selection can have a profound impact on pathologic findings and ultimate outcome. In addition, salvage treatment is frequently initiated at the time of biochemical relapse rather than clinical recurrence. Consequently, patterns of failure can be significantly altered compared to previous times when PSA was not available. To better understand the impact of PSA on pathologic findings, outcome, and salvage treatment, we reviewed our experience in the PSA era with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. METHODS AND MATERIALS: Between 1987 and 1993, 423 cases could be identified with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. The distribution of cases by pretreatment PSA levels was as follows: < or = 4 ng/ml (18%), 4-10 ng/ml (42%), 10-20 ng/ml (21%), > 20 ng/ml (14%), and unknown (5%). The median pretreatment PSA level for the entire group was 8.0 ng/ml. Sixteen patients received adjuvant or neoadjuvant androgen suppression and 13 received postoperative radiotherapy. Only 31 patients (7%) had pathologically positive pelvic lymph nodes. The overall margin involvement rate was 46%. Fifty-three percent of patients had surgical Gleason scores > or = 7, and 65% had extracapsular extension. The median follow-up time was 41 months. RESULTS: The projected overall survival at 7 years after surgery was 90%. The 5-year clinical relapse-free survival rate was 84%. At 5 years, the local control and distant failure rates were 92% and 91%, respectively. Biochemical relapse was defined as a detectable or rising PSA level after prostatectomy. The 5-year biochemical relapse-free survival (bRFS) rate was 59%. The 5-year RFS was 88% in patients with preoperative PSA levels < or = 4, 62% for 4-10, 48% for 10-20, and 31% for > 20. Combining the two independent preoperative variables, iPSA and biopsy GS (bGS), two risks groups were defined: low risk [initial PSA (iPSA) levels < or = 10.0 and bGS < or = 6] and high risk (iPSA levels > 10.0 ng/ml or bGS > or = 7). The 5-year bRFS rate for the low-risk cases was 81% vs. 40% for high-risk cases (p < 0.001). On multivariate analysis, three factors independently predicted biochemical relapse: iPSA levels (p = 0.005), Gleason score from the surgical specimen (sGS) (p = 0.002), and positive surgical margins (p < or = 0.001). The 5-year bRFS rates for margin positive vs. margin negative patients were 37% vs. 78%, respectively. The 5-year bRFS rates for GS > or = 7 vs. GS > or = 6 were 42% vs. 80%, respectively. All clinical relapses were accompanied by a rise in PSA. In patients who manifested biochemical failure followed by a clinical failure, the median interval between the PSA rise and clinical failure was 19 months (range 7-71). Margin involvement was the only independent predictor of local failure (p = 0.019). The 5-year local failure-free survival for negative margin cases was 96% vs. 87% for positive margin cases (p = 0.012). Lymph node (LN) involvement and high-risk group were the two independent predictors of distant failure. The 5-year distant failure-free survival for negative LN cases was 94% vs. 67% for positive LN cases (p < 0.001). The 5-year distant failure-free survival for low-risk cases was 97% vs. 85% for high-risk cases (p = 0.005). For the 124 patients failing biochemically, 85 were observed and 39 were treated either with radiation or androgen deprivation. With a median follow-up of 32 months, the clinical disease relapse-free survival was 79% for the treated patients vs. only 32% for the patients observed (p < 0.001). CONCLUSION: Pretreatment PSA is the most potent clinical factor independently predicting biochemical relapse, thereby allowing markedly better case selection. Achieving negative margins, even in relatively advanced disease, provides excellent lon     

Bone metabolism and phosphorus metabolism in patients with prostate cancer: paracrine and endocrine effects produced by prostate neoplasm

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P < 0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p < 0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P < 0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.     

Chlormadinone acetate withdrawal syndrome under combined androgen blockade for advanced prostate cancer

Between July 1991 and December 1994 at Tsukuba Gakuen Hospital, we treated 19 consecutive men with advanced adenocarcinoma of the prostate (five at stage C, four at stage D1 and 10 at stage D2). Of these, 14 patients underwent castration (two patients) or received LH-RH analogue (12 patients) plus chlormadinone acetate for combined androgen blockade. We report three representative cases of sequential prostate specific antigen (PSA) elevation following initial response to this combined androgen blockade. Discontinuation of chlormadinone acetate resulted in decline of the serum PSA level. This suggests that trial chlormadinone acetate withdrawal in patients showing increasing levels of PSA during combined androgen blockade should be considered before initiation of alternative treatment.     

Suprascapular nerve rotator cuff compression syndrome in volleyball players

OBJECTIVE AND DESIGN: Eighteen active acromegalics entered a prospective open study with cabergoline (CAB), a dopaminergic drug much more potent than bromocriptine (Br). METHODS: CAB was administered for 6 months at doses ranging between 0.5 mg twice weekly and 0.5 mg/day. Clinical-anamnestic characteristics of the patients were: (i) sensitivity to dopamine agonist drugs (10 patients); (ii) resistance to somatostatin analogs (SAs) (8 patients): (iii) intolerance to SA (3 patients). In 2 patients marked hyperprolactinemia was present. RESULTS: Basal GH was 6.6 microg/l (2.2-50) (median (range)), and on treatment it was 3.5 microg/l (1.2-34) (P=0.013). The corresponding IGF-I values were 720 microg/l (410-1438) and 375 microg/l (167-1260) respectively (P=0.00001). Individual GH levels decreased below 2 microg/l in 5 patients, and between 2 and 5 microg/l in another 5 patients. IGF-I levels were suppressed below 50% of baseline in 8 patients and normal age-adjusted IGF-I values were reached in 5 patients (27% of the series). The retrospective comparison with previous chronic treatment with Br in the 10 suitable patients showed a greater effectiveness of CAB (IGF-I decrease on CAB treatment, 46.8%, on Br treatment, 31%, P=0.02). Adenoma shrank in the 3 patients whose pituitary imaging was repeated during CAB. CONCLUSIONS: These results envisage that CAB may represent a worthy therapeutic tool in acromegalic patients, inducing a degree of IGF-I and GH suppression comparable to SAs, administered by the oral route and much less expensive.     

Final results of complete hormone blockade versus monotherapy in prostatic metastatic cancer. PSA implications

Of 102 patients with metastatic prostate cancer, 52 were treated with orchidectomy and 50 with CHB; 22 of these received a LHRH analog + Flutamide and 28 orchidectomy + Flutamide. No differences were seen in either arm in terms of age (69.9 vs 70.2 years) or initial PSA (493.3 vs 486.5 ng/ml) variables. After three months treatment, CHB achieved a decrease of PSA higher than monotherapy (52.9 vs 34.5 ng/ml) p<0.01 as well as minimum PSA level during follow-up (41.2 vs 17.5 ng/ml) (p<0.001). Initial clinical response rates were higher in the group treated with complete blockade (42.3% vs 52%) (p=n.s.). Overall, no significant differences were seen between the actuarial curves of biological progression, clinical progression and survival, with expected mean values of 13 vs 12, 14 vs 15 and 34 vs 28 months, respectively. However, when survival was considered as a function of bone disease dissemination, a greater survival rate was seen in patients with minimal M1 disease (p<0.05), and there were no differences between the M2 and M3 arms.     

Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for detecting prostate cancer in patients with prostatism and intermediate PSA levels

OBJECTIVE: To investigate the clinical significance of the free-to-total prostate-specific antigen (PSA) ratio in improving the specificity of PSA measurement for detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL total PSA) in patients referred for the treatment of urinary symptoms. PATIENTS AND METHODS: Serum samples were obtained from 333 consecutive patients with obstructive and irritative urinary symptoms. Of these men, 114 had total PSA levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH and a chronic indwelling catheter. The concentrations of free and total PSA (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1-antichymotrypsin were measured and the free-to-total PSA ratio calculated. All patients under 70 years of age or with suspicious findings on digital rectal examination or transrectal ultrasonography underwent ultrasound-guided sextant prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral resection of the prostate and six (5%) radical retropubic prostatectomy. RESULTS: Patients in group 1 had significantly lower median free PSA concentrations (0.78 ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs 19.9%, P < 0.001) than those in group 2. The differences were similar between group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free-to-total PSA ratio 18.7%, P = 0.007). There were no significant differences between patients in groups 2 and 3. The free-to-total PSA ratio had a higher specificity than total PSA at all sensitivity levels, e.g. a threshold free-to-total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46% (group 3) from unnecessary biopsies. The area under the receiver operating characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free-to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81 (free-to-total PSA ratio). CONCLUSION: In those patients with extensive symptoms from BPH and requiring surgical treatment, the free-to-total PSA ratio improves the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4-10 ng/mL total PSA. This improvement occurred in patients with or without a chronic indwelling catheter for urinary retention.     

Pathologic features from prostate needle biopsy and prognosis after I-125 brachytherapy

To evaluate the role of detailed pathologic features in predicting outcome for early-stage prostate cancer treated with I-125 brachytherapy. The pretreatment biopsy slides of 103 patients with T1/T2 and Gleason scores of 4-7 prostatic carcinoma, which was treated by transperineal I-125 implantation, were reviewed retrospectively by a single pathologist (P.B.G.). Biochemical tumor control rates [prostate-specific antigen (PSA) below 1.0] were correlated with pretreatment PSA, Gleason score, the amount of tumor in the biopsy samples, and the presence of perineural invasion. In Cox proportional-hazard, multivariate analysis, the strongest predictors of failure were pretreatment PSA above 10 ng/ml (P = 0.013) and the length of the biopsy specimen replaced by tumor (P = 0.15). The percent of biopsy tissue replaced by tumor (P = 0. 74), perineural invasion (P = 0.78), and Gleason score (P = 0.66) were less predictive of prognosis. It was concluded that pretreatment PSA is the strongest predictor of biochemical failure. Detailed assessment of pathological features on needle biopsy added little prognostic information beyond that of pretreatment PSA alone. Like all other prognostic parameters for prostate cancer, there is considerable overlap in pathologic features between those patients who will or will not be controlled biochemically.     

Retained glass foreign bodies in wounds: predictive value of wound characteristics, patient perception, and wound exploration

This report describes associations of demographic and health-related characteristics with use of prostate cancer screening. Data are from a random-digit dial survey of Washington State residents. Analyses are restricted to men ages 40-79 years (n = 332) and examine both digital rectal examination (DRE) and blood tests for prostate-specific antigen (PSA) in the previous 2 years. Results are adjusted to be representative of the state's population. In 1996, 53.6% of men received either DRE, PSA, or both. Among those screened, 42% received DRE alone, 15% PSA alone, and 43% both PSA and DRE, and the percentages of men receiving PSA increased markedly with age (30%, ages 40-49 years; 58%, ages 50-59 years; and 77%, ages 60-79 years). After control for other demographic characteristics, the relative odds for any prostate cancer screening were 5.5 for ages 60-79 versus 40-49 years, 2.4 for 16+ versus < or = 12 years of education, and 4.0 for 2+ versus no physician visits in the previous 2 years (all P < 0.05). Characteristics generally associated with good health, including regular exercise and low fat and high fruit and vegetable intakes, were also significantly associated with prostate cancer screening. In conclusion, in 1996, approximately one-half of the men in Washington State over age 40 years had received prostate cancer screening in the previous 2 years. Few men were screened with PSA alone, and the use of PSA as part of prostate cancer screening increased markedly with age. Because PSA screening increases detection of prostate cancer, epidemiological studies of health behavior and cancer risk must carefully control for screening history to avoid detection bias.     

Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study

PURPOSE: We compare the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for pelvic confined prostate cancer, that is T1-4, pN0-3, M0 (TNM classification). MATERIALS AND METHODS: In this prospective study 91 patients with clinically localized prostate cancer were, after surgical lymph node staging, randomized to receive definitive external beam radiotherapy (46) or combined orchiectomy and radiotherapy (45). Patients treated with radiotherapy alone had androgen ablation at clinical disease progression. The effects on progression-free, disease specific and overall survival rates were calculated. RESULTS: After a median followup of 9.3 years (range 6.0 to 11.4) clinical progression was seen in 61% of the radiotherapy only patients (group 1) and in 31% of the combined treatment patients (group 2) (p = 0.005). The mortality was 61 and 38% (p = 0.02), and cause specific mortality was 44 and 27%, respectively (p = 0.06), in groups 1 and 2. The differences in favor of combined treatment were mainly caused by lymph node positive tumors. For node negative tumors there was no significant difference in survival rates. CONCLUSIONS: The progression-free, disease specific and overall survival rates for patients with prostate cancer and pelvic lymph node involvement are significantly better after combined androgen ablation and radiotherapy than after radiotherapy alone. These results strongly suggest that early androgen deprivation is better than deferred endocrine treatment for these patients.     

Impact of androgen deprivation prior to radical prostatectomy for T1, T2 prostate cancer on the likelihood of curative surgery

BACKGROUND: Extracapsular extension is commonly seen in patients undergoing radical prostatectomy for localized prostate cancer due to understaging of disease. One possible approach to reduce the likelihood of extracapsular disease is androgen deprivation prior to radical prostatectomy, neoadjuvant therapy. However, adequate application is not clear. We analyzed the outcome of neoadjuvant therapy and radical prostatectomy in an attempt to expand our understanding on indications of neoadjuvant therapy. METHODS: Forty-six selected patients with clinical T1 or T2 prostate cancer were retrospectively reviewed. Twenty-two patients underwent neoadjuvant therapy (group N) that mainly consists of LH-RH agonist. The duration of neoadjuvant therapy, varied from 1 to 12 months with the mean being 4 months. Twenty-four underwent radical prostatectomy alone (group S). RESULTS: In the group N and group S, 59% and 33% had either organ confined disease (OCD) or specimen confined disease (SCD) respectively. When the patients had OCD or SCD, they were defined as surgically cured patients. In the patients with clinical stage T1b, T1c, and T2 disease, likelihood of surgical cure were 100%, 50%, 46.7% in group N, 100%, 20%, 11%, in group S respectively. In the patients with initial serum PSA less than 10 ng/ml and more than 10.1 ng/ml, likelihood of surgical cure were 83.3% and 50% in group N, 63.6% and 15.4% in group S, respectively. Likelihood of surgical cure was higher in the patients with well differentiated carcinoma both in group N and group S. All the patients with serum PSA less than 0.1 ng/ml after neoadjuvant therapy had OCD. CONCLUSION: Neoadjuvent therapy could be beneficial either in the patients with moderately or in the poorly differentiated adenocarcinoma of prostate especially in the group with initial serum PSA more than 10.1 ng/ml. However, in patients both with well differentiated adenocarcinoma and the initial serum PSA less than 10 ng/ml, no evidence of beneficial effect on the likelihood of OCD or SCD was observed. PSA after neoadjuvant therapy could be useful predictor for the pathological outcome.     

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.