Postoperative Prostate-specific Antigen Research Articles

Prognostic Value of Preoperative Serum Cell-Free Circulating DNA in Men with Prostate Cancer Undergoing Radical Prostatectomy

We evaluated the association of preoperative serum cell-free circulating DNA concentration in men with clinically localized prostate cancer who underwent radical prostatectomy with prostate-specific antigen (PSA) recurrence. One hundred and ninety-two men with clinically localized prostate cancer, who underwent radical prostatectomy at the Johns Hopkins Hospital and had preoperative serum available for analyses constituted our study population. All serum samples were collected before prostate biopsy or at least 4 months after prostate biopsy. The total amount of serum cell-free circulating DNA from each sample was calculated using a standard curve generated via quantitative real-time PCR. PSA recurrence was defined as a single postoperative PSA level of > or =0.2. The natural logarithm (ln) of the DNA concentration was used for statistical analyses. Of the 192 men in our study, 56 (29%) experienced PSA recurrence within the study period (median time to PSA recurrence 2 years). The median follow-up time for men free of disease at last follow-up was 3 years. The median serum cell-free DNA concentration of all men in the study was 5.3 ng/mL (mean 18.05 ng/mL; range 0.2-320 ng/mL). The mean serum DNA concentration for men who recurred and for those who did not was 3.8 +/- 34.1 and 13.7 +/- 33.6 ng/mL, respectively (P = 0.001). In a univariate analysis, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 1.49; 95% confidence interval, 1.3-1.8; P < 0.001). In the multivariate model, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 2.56; 95% confidence interval, 1.1-1.6; P = 0.003). Using bootstrap analyses, serum cell-free DNA concentrations > or =5.75 ng/mL were associated with an increased risk of PSA recurrence within 2 years of radical prostatectomy. Our study suggests that preoperative serum cell-free DNA concentration may be a useful prognostic biomarker for men with clinically localized prostate cancer treated with radical prostatectomy.

Benefit on Biochemical Control of Adjuvant Radiation Therapy in Patients with Pathologically Involved Seminal Vesicles after Radical Prostatectomy

To determine whether there is a benefit for biochemical control with adjuvant radiation therapy to the surgical bed following radical prostatectomy in patients with seminal vesicle invasion and pathologically negative pelvic lymph nodes (pT3b-pT4 pN0). We retrospectively reviewed the clinical records of radical prostatectomy patients treated between 1995 and 2002. A total of 66 patients with seminal vesicle invasion were identified: 45 of these patients received adjuvant radiation therapy and 21 were observed. Radiation therapy was initiated within 4 months of prostatectomy. Median dose was 66 Gy (range, 60-70 Gy). Median follow-up from the day of surgery was 40.6 months (mean, 41.5; range, 12-99). Biochemical recurrence was defined as the first value > or = 0.2 ng/ml. At two years, the proportion of patients free from biochemical recurrence was 80% in patients who received adjuvant radiation therapy versus 54% for those not given radiation therapy (P = 0.036). Actuarial biochemical recurrence at 5 years was 59% vs 41% for the radiation therapy and no radiation therapy groups, respectively. On univariate Cox regression model, the hazard of biochemical failure was also associated with a detectable (> or = 0.2 ng/ml) postsurgical prostate-specific antigen (P = 0.02) prior to radiation therapy. Pathological T stage (pT3b vs pT4), Gleason score, primary Gleason pattern and positive surgical margins were not significantly associated with biochemical recurrence. The hazard of biochemical failure was around 85% lower in the radiation therapy group than in the observation group (P = 0.002). Data from the present series suggest that adjuvant radiation therapy for patients with seminal vesicle invasion and undetectable (< or = 0.2 ng/ml) postoperative prostate-specific antigen significantly reduces the likelihood of biochemical failure.

Predictive Factors for Progression in Patients with Clinical Stage T1a Prostate Cancer in the PSA Era

ObjectiveIn the literature, most data regarding the outcome of patients with clinical stage T1a prostate cancer were established before the prostate-specific antigen (PSA) era. The aim of our study was to determine the predictive factors of progression in patients with T1a prostate cancer diagnosed in the PSA era. MethodsConsecutive patients (n=144) with newly diagnosed T1a prostate cancer (tumor involving ≤5% of the resected prostatic tissue) were included. None of them was treated before evidence of tumor progression confirmed by prostate needle biopsies. The associations between tumor characteristics and time to cancer progression were assessed using Cox regression analysis. ResultsWith a mean follow-up of 5.1 yr, 30 patients (21%) experienced cancer progression. Five adverse parameters were significantly associated with cancer progression: preoperative PSA≥10ng/ml, postoperative PSA≥2ng/ml, prostate weight ≥60g, weight of resected tissue ≥40g, and Gleason score≥6. The 5-yr progression rate was 12% if fewer than two of these parameters were present, whereas it was 47% if two or more parameters were present (p<0.001). ConclusionIn the PSA era the risk of progression associated with T1a prostate cancer can be predicted using five criteria, and two groups of patients can be defined. The patients at low risk of progression may be good candidates for surveillance. In those with a high risk of progression, a more aggressive treatment should be discussed.

Preoperative platelet-derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation in high-risk localized prostate cancer

5141 Background: Reduction in tumor interstitial fluid pressure with platelet-derived growth factor receptor (PDGFR) inhibitor therapy in experimental systems improves drug delivery and the therapeutic index of taxane chemotherapy (Pietras, Cancer Research, 2002). We hypothesized that PDGFR inhibitor therapy with imatinib mesylate combined with androgen ablation (AA) and docetaxel (D) induces pathological complete responses (pCR) in high-risk localized prostate adenocarcinoma (PC) prior to radical prostatectomy and pelvic lymph node dissection (RP). Methods: Thirty six men with PC ≥T2 disease or Gleason grade 8–10 or serum prostate-specific antigen (PSA) &gt; 20 ng/ml or cT2b and PSA &gt;10 ng/ml and Gleason 7 disease (AJCC, 1992), without radiological evidence of metastases, were planned to receive intramuscular leuprolide, imatinib 600mg orally daily, and weekly D 30 mg/m2 on D1, 8, 15, 22 q42 for three cycles (18 weeks) before RP [β (0.02, 1.98) prior on the possibility of pCR]. Unresectable pelvic nodal disease, post-operative PSA &gt; 0.2 ng/ml or administration of post-operative radiation or AA were defined as treatment failure. Results: Between 6–03 and 9–04, 39 men were registered; median age 57 years (range, 44–71); 35 Caucasian, 2 Hispanic, 4 African-American. Risk factors included T3 disease (22/39), Gleason 8–10 disease (31/39), PSA &gt; 20 ng/ml (12/39). Three men were ineligible or declined therapy; 29/36 (80%) received three cycles of therapy; 7/36 (20%) discontinued therapy related to toxicity. Grade 3–4 toxicity included rash (n=3), diarrhea (n=5), fatigue (n=3), neutropenia (n=2), hepatic (n=1). Severe or unexpected surgical complications were not encountered. No pCRs were defined; 15/36 (42%) have PSA &lt; 0.2 ng/ml [12/36 (33%), &lt;0.1 ng/ml] at 24 months and 13/36 (36%) met definition for treatment failure. Conclusions: The addition of the PDGFR inhibitor imatinib to pre-operative AA and D, although feasible, did not induce pCR in PC. [Table: see text]

Focal Cryosurgery: Encouraging Health Outcomes for Unifocal Prostate Cancer

Owing to the ability to better detect small-volume tumors, we have seen an increasing population of men with low-risk unifocal prostate cancer. We report our safety and efficacy experience of focal cryoablation of the prostate to maintain potency and preserve genitourinary function in men with localized, unifocal disease. From June 2002 to December 2005, 25 patients with primary unifocal prostate cancer were treated with focal cryoablation of the prostate. The patients were followed up with physical examinations, morbidity questionnaires, and prostate-specific antigen (PSA) determinations every 3 months for the first year and every 6 to 12 months thereafter. Patients with a PSA nadir greater than 1.0 ng/mL or a nadir plus 2 ng/mL underwent repeat biopsy to assess for cancer recurrence. The median age was 68 years (range 48 to 78). The median preoperative PSA level was 6.0 ng/mL, and the postoperative PSA nadir was 2.4 ng/mL. The median follow-up was 28 months. Seventeen patients remained potent. No patients reported worsened lower urinary tract symptoms, incontinence, rectal pain, perineal discomfort, or fistula formation. The median PSA nadir was 2.4 ng/mL, and 40% of patients had a PSA nadir of less than 1.0 ng/mL. Of the 25 patients, 21 (84%) had not experienced biochemical failure, defined as a greater than 50% PSA nadir reduction. Seven patients underwent repeat biopsy, and prostate cancer was detected in the contralateral gland in 2 patients and in the area of previous cryosurgery in 1 patient. Focal cryoablation of the prostate has exhibited minimal morbidity and promising efficacy in our 3-year observation. Longer follow-up is necessary to determine its role in the treatment of patients with low-risk unifocal prostate cancer.

Prostate Cancer Metastatic to the External Auditory Canals

A 58-year-old white man with prostate-specific antigen (PSA) level of 6 ng/mL, a Gleason score of 6 (3+3), and T2a adenocarcinoma of the prostate underwent prostatectomy. On review of the pathology, the specimen contained a Gleason score of 8 (3+5) with other high-risk features. The patient had a persistently elevated postoperative PSA level and was placed on total androgen blockade. The PSA continued to increase, and the patient developed bone-only metastatic disease. The patient was treated with palliative external-beam radiation and samarium. Six months later, he presented with bilateral hearing loss and was found to have pathologic and radiographic evidence of metastatic prostate cancer to the external auditory canals. This was an unusual late finding. The patient died shortly afterward before completing palliative treatment to the area

Death in Patients With Recurrent Prostate Cancer After Radical Prostatectomy: Prostate-Specific Antigen Doubling Time Subgroups and Their Associated Contributions to All-Cause Mortality

Among patients with biochemical recurrence after radical prostatectomy, we found previously that postoperative prostate-specific antigen doubling time (PSADT) was associated with risk of prostate cancer death. However, given the small number of patients in the highest risk PSADT subgroup, it is unclear which PSADT subgroups contribute the greatest to prostate cancer-specific death and how this influences all-cause mortality. This study was a retrospective analysis of 379 patients treated with radical prostatectomy between 1982 and 2000 who had a biochemical recurrence and PSADT data available. Mean and median follow-up after surgery was 11.4 (standard deviation, 5.4) and 11.0 years, respectively (range, 1.6 to 23.0 years). Shorter PSADT was significantly associated with prostate cancer-specific and all-cause mortality (P < .001). Although patients with a PSADT less than 3 months were at the greatest risk of death, because of the limited number of patients in this group, they accounted for only 13% of prostate cancer deaths at 15 years after biochemical recurrence, whereas patients with an intermediate PSADT (3.0 to 8.9 months) accounted for 58% of all prostate cancer deaths. Among patients with a PSADT less than 15 months, prostate cancer accounted for 90% of all deaths. Only patients in the slowest PSADT subgroup (> or = 15 months) had a greater risk of competing-causes mortality compared with that from prostate cancer. Among a select cohort of young, healthy patients with PSA recurrence after radical prostatectomy and a PSADT less than 15 months, prostate cancer accounted for an estimated 90% of all deaths by 15 years after recurrence. The majority of prostate cancer deaths occurred among patients with an intermediate PSADT (3.0 to 8.9 months).

Spurious prostate‐specific antigen (PSA) recurrence after radical prostatectomy: Interference by human antimouse heterophile antibodies

Human antimouse heterophile antibodies (HAMA) are naturally occurring antibodies that can interfere with modern serum assays. We report a case of HAMA interference with a commonly used prostate-specific antigen (PSA) assay, leading to false elevation (2.17-2.46 ng/mL) after radical prostatectomy. Pre-operative PSA was 4.4 ng/mL, and final pathology was Gleason 3 + 3, pT2cNXMX. This markedly elevated postoperative PSA led to unnecessary imaging for metastasis and psychological distress to the patient. Direct measurement of HAMA in the patient's serum yielded a value of 440 ng/mL (<74 ng/mL). An alternate PSA assay using goat detection antibody eliminated interference, with all values 0.05 ng/mL. When a patient's PSA is inconsistent with the clinical scenario, one should consider immunological interference by HAMA in PSA assays.

Time to an undetectable prostate‐specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer‐specific mortality

For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA) recurrence, whether the time to an undetectable (u) PSA was significantly associated with prostate cancer-specific mortality (PCSM) was evaluated. The study cohort comprised 585 men with a rising PSA and negative bone scan after surgery (n = 415) or radiation therapy (n = 170) that were treated with AST and achieved a uPSA. Gray's regression was used to evaluate whether the time to a uPSA after AST was significantly associated with the time to PCSM after the uPSA adjusting for known prognostic factors. The median time (interquartile range) to achieve a uPSA was 4.6 (range, 2.8-7.8) months. There were 23 deaths, 4 of which were from prostate cancer. An increasing time to a uPSA (adjusted hazard ratio [HR]: 9.2, 95% confidence interval [CI]: 3.8, 22.1; P < .0001), a decreasing PSA doubling time (DT) (HR: 0.58, 95% CI: 0.43, 0.80; P = .0007), and Gleason score 8 to 10 cancers (HR: 8.6, 95% CI: 1.04, 77; P = .05) were significantly associated with a shorter time to PCSM. Despite achieving a uPSA after AST, the risk of PCSM increased significantly as the time to the uPSA lengthens, especially in men with a short pre-AST PSA DT and high-grade prostate cancer. These men should be considered for randomized studies evaluating immediate vs delayed chemotherapy after the achievement of the uPSA.

Prostate-Specific Antigen Control with Low-Dose Adjuvant Radiotherapy for High-Risk Prostate Cancer

To analyze the prostate-specific antigen (PSA) outcome after low-dose adjuvant RT at a single institution, because the role and optimal dose of external beam radiotherapy (RT) after radical prostatectomy for prostate cancer remain controversial. We retrospectively identified 65 men who had received low-dose adjuvant RT (median 50 Gy) for microscopically positive margins with an undetectable postoperative PSA from 1990 to 2004. Biochemical failure-free survival was the primary endpoint. Biochemical failure was defined as two consecutive PSA increases to greater than 0.2 ng/mL. At a median follow-up of 5 years, 2 men had developed distant metastasis, 2 had local recurrence, and 2 had died (neither attributable to prostate cancer). Biochemical failure had occurred in 7 men (11%). The 5 and 8-year rate of biochemical failure-free survival was 87%. A greater Gleason score (P = 0.04) and seminal vesicle invasion (P = 0.04) predicted significantly for increased biochemical failure on univariate analysis. No single factor was significant on multivariate analysis. Men with a Gleason score of 7 or less had a 5-year biochemical failure-free survival rate of more than 90%. In contrast, those with a Gleason score of 8 or more had a 50% risk of biochemical failure at 5 years. Acute bowel or bladder toxicity (all grade 2 or less) developed in 25%. Two men developed chronic urethral stricture requiring dilation, and 34 (51%) developed surgery-related toxicity that persisted throughout and after RT. Low-dose RT is well tolerated and can potentially provide PSA control in men with Gleason score 7 or less disease with positive surgical margins after radical prostatectomy.

Changes in the Serum Prostate-specific Antigen Level One Year after Transurethral Resection of the Prostate

Purpose: We wanted to investigate how transurethral resection of the prostate (TURP), for treating patients with benign prostate hyperplasia (BPH), affected the serum prostate-specific antigen (PSA) levels. Materials and Methods: The serum PSA levels were measured before and 12 months after operation in 57 patients who underwent TURP for BPH. The total prostate weight, as measured by transurethral ultrasonography (TRUS), and the weight of the surgical specimen were examined in relation to the pretreatment PSA value and the changes in the PSA levels after the operation. Results: The preoperative mean PSA density was 0.10±0.08ng/ml/cc. The postoperative serum PSA levels were decreased significantly after TURP (p=0.002). Removal of 1g of BPH tissue reduced the serum PSA levels by an average of 0.22±0.4ng/ml. The changes in the serum PSA level one year after TURP correlated with the resected chip weights [Y=0.406+0.176x (r=0.526, p<0.05)]. Conclusions: TURP caused a long term decrease in the serum PSA level. One year after TURP, the PSA levels should be expected to decrease according to the resected chip weights. (Korean J Urol 2007;48:691-695) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Implications of circulating chromogranin A in prostate cancer

To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. 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. 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). 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.

MP-21.10: Postoperative prostate specific antigen (PSA) decline can predict the adequacy of adenoma removal with BPH surgical techniques

PSA, in patients with BPH, is correlated with total prostate and transition zone volume In many techniques no tissue is retrieved therefore PSA decline may be a surrogate for adequacy of surgical treatment.

Time to Prostate Specific Antigen Recurrence After Radical Prostatectomy and Risk of Prostate Cancer Specific Mortality

In patients treated with radical prostatectomy who have biochemical recurrence we have previously reported that time from surgery to biochemical recurrence and postoperative prostate specific antigen doubling time are significantly related to the risk of prostate cancer death. We performed a more thorough examination of the association of time from surgery to biochemical recurrence and the risk of prostate cancer death. We retrospectively studied the records of 379 patients treated with radical prostatectomy between 1982 and 2000 who had had biochemical recurrence. We examined the association of time from surgery to prostate specific antigen recurrence and prostate specific antigen doubling time, and the risk of prostate cancer death using the Spearman correlation and Cox proportional hazards regression, respectively. Longer time from surgery to prostate specific antigen recurrence was associated with a slower prostate specific antigen doubling time (Spearman r = 0.36, p < 0.001) and a decreased risk of prostate cancer death (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001). The 15-year actuarial prostate cancer specific survival rate after biochemical recurrence in patients with recurrence at 3 years or less was 41% (95% CI 29 to 53) compared to 87% (95% CI 75 to 93) in patients with recurrence more than 3 years after radical prostatectomy. On multivariate analysis a shorter time from surgery to prostate specific antigen recurrence was associated with an increased risk of prostate cancer death (3 or less vs more than 3 years, RR 2.70, 95% CI 1.37 to 5.31, p = 0.004). Earlier prostate specific antigen recurrence is associated with an increased risk of prostate cancer death. These data suggest that perhaps time to prostate specific antigen recurrence may be a reasonable intermediate end point in patients treated with radical prostatectomy, although this must be validated in other studies.

Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality

Objectives To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. Methods From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray’s P value. Results Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1% versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction ( P <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower ( P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). Conclusions Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community.

Characterization of Biochemical Recurrence after Radical Prostatectomy

Background: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). Methods: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. Results: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. Conclusions: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.

Detectable Prostate Specific Antigen Between 60 and 120 Days Following Radical Prostatectomy for Prostate Cancer: Natural History and Prognostic Significance

Following radical retropubic prostatectomy for prostate cancer, if the serum prostate specific antigen fails to become undetectable, occult micrometastatic disease is suspected. We assessed the natural history of disease progression, and predictors of recurrence and survival in this group of patients. We identified 303 men treated with radical retropubic prostatectomy for prostate cancer between 1990 and 1999, who had a detectable prostate specific antigen between 60 and 120 days postoperatively. Systemic recurrence-free and cancer specific survival were estimated using the Kaplan-Meier method, and analyzed using Cox proportional hazards models. Clinical and pathological features were more adverse among men whose postoperative prostate specific antigen was detectable. These men had poorer systemic recurrence-free survival and cancer specific survival compared to men with an undetectable postoperative prostate specific antigen, and even men whose prostate specific antigen subsequently became detectable. These differences persisted after multivariate adjustment for preoperative prostate specific antigen, specimen Gleason score, seminal vesicle and margin status. With a median followup of 8.5 years, 50 systemic recurrences and 26 deaths from cancer were observed. Gleason score and the prostate specific antigen doubling time were multivariate predictors of systemic recurrence, while Gleason score, margin status and seminal vesicle invasion were predictors of death from cancer. A detectable prostate specific antigen immediately following radical retropubic prostatectomy confers an increased risk of progression and death, but only in a subset of patients, who may be identified on the basis of pathological features and prostate specific antigen doubling time. In future such patients may be suitable for trials of systemic therapy.

Cancer-specific survival following radical prostatectomy or radiation therapy and short course hormonal therapy in men with localized, unfavorable-risk prostate cancer

4572 Background: We estimated prostate cancer-specific mortality (PCSM) rates following radical prostatectomy (RP) or external beam radiation therapy (RT) and 6 months of androgen suppression therapy (AST) in men with unfavorable-risk prostate cancer. Methods: Between 1981 and 2002, 3,240 men with intermediate- (T2b or Gleason score 7 or prostate-specific antigen (PSA) &gt; 10 to 20 ng/mL) or high-risk (T2c or Gleason score 8 to 10 or PSA &gt; 20 ng/mL) prostate cancer were treated with RP (n = 2,690) or RT+AST (n = 550) and comprised the study cohort. If PSA failure occurred, defined by a postoperative PSA level &gt; 0.2 ng/mL and rising or by the ASTRO definition following RT+AST, then men received salvage RT or life-long AST, respectively. Life-long AST was initiated if PSA failure occurred after salvage RT. Imaging of the pelvis and skeleton was negative for metastases at the time of any salvage therapy. Gray’s formulation was used to compare the cumulative incidence estimates of PCSM and to calculate the adjusted hazard ratios (HR) and associated 95% confidence intervals for initial treatment and known prognostic factors. Results: After a median follow-up time for living patients of 4.5 and 4.2 years for the RP and RT+AST cohorts, respectively, there were no significant differences in the estimates of PCSM following RP or RT+AST in men with intermediate- (p = 0.44) or high-risk (p = 0.26) disease. As shown in the Table , after adjusting for PSA level, Gleason score, and T-category, initial therapy was not significantly associated with PCSM for men with intermediate- (HR: 1.2 [95% CI: 0.3, 4.3]; p = 0.78) or high-risk (HR: 1.2 [95% CI: 0.5, 2.8]; p = 0.62) disease. Conclusion: Men with localized, unfavorable-risk prostate cancer who receive RT and short course AST as initial therapy appear to have similar PCSM rates as men who undergo initial RP followed by salvage RT and life-long AST after first and second PSA failure, respectively. [Table: see text] No significant financial relationships to disclose.

Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients

We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion. Kaplan–Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation.

Cryosurgery for prostate cancer: How I do it

Background: Cryosurgery for prostate cancer is the ablation of the cancer by inducing a lethal freezing temperature (−40°C) to kill the cancer cells. This is now one of the optional curative treatments for localized prostate cancer patients.Methods: A third generation cryotherapy machine was used. An ultrathin 17 Fr cryoneedle was used to puncture the prostate gland transperineally under real‐time transrectal ultrasound guidance. Cryogen gas, using argon, was used for active freezing and helium gas was used for active thawing. Thermoprobes were used to ensure the lethal temperature was reached. A urethral warmer device was necessary to reduce urethral damage. Foley catheterization was necessary for 2–3 days postoperatively.Results: Postoperative prostate specific antigen (PSA) level was monitored 3 monthly. Biochemical success (PSA &lt; 0.4) can be achieved in most cases.Conclusion: This new cryoablation of prostate cancer can provide a minimally invasive option for localized prostate cancer patients.