Postoperative Prostate-specific Antigen Research Articles

Natural History of Biochemical Recurrence After Radical Prostatectomy with Adjuvant Radiation Therapy

We evaluated the long-term outcome of patients with biochemical recurrence following radical prostatectomy with adjuvant radiation therapy and determined predictors of systemic progression in these men. We identified 134 men with biochemical recurrence following radical prostatectomy plus adjuvant radiation therapy for pT(any)N0M0 disease. Median followup was 13.1 years. Survival after biochemical recurrence was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze clinicopathological variables associated with systemic progression after biochemical recurrence. Overall, 41 patients (31.5%) with biochemical recurrence experienced systemic progression and 57 (42.5%) died, including 19 (14.2%) of prostate cancer. Median systemic progression-free and cancer specific survival were not attained at 15 years of followup after biochemical recurrence. Median time from prostatectomy to recurrence was 3.3 years. Ten-year cancer specific survival was not significantly different for patients who experienced biochemical recurrence less and greater than 3.3 years after radical prostatectomy (83% and 83%, respectively, p = 0.39). Moreover, on multivariate analysis increased pathological Gleason score (HR 1.78, p = 0.02) and rapid prostate specific antigen doubling time (less than 6-month doubling time HR 11.39, p <0.0001) were significantly associated with the risk of systemic progression. The natural history of biochemical recurrence after radical prostatectomy plus adjuvant radiation therapy is heterogeneous with only a minority of these men experiencing systemic progression and death from prostate cancer. The decision to begin additional therapies in such patients must balance the risk of disease progression, based on pathological Gleason score and postoperative prostate specific antigen doubling time, against the cost and morbidity of treatment.

A 66-Year-old Man With Prostate-specific Antigen Recurrence and Lung Mass After Radical Prostatectomy

A67-year-old white male patient with a past medical history of prostate cancer status post nervesparing radical retropubic prostatectomy, malignant fibrohistiocytoma of the left hand, and basal cell carcinoma of the ear status post resection, presented for a follow-up visit to his urologist and was found to have an increased prostate-specific antigen (PSA). The patient had initially undergone a radical prostatectomy in December 1989 when he was 60 years old. Final pathology revealed a Gleason 6 adenocarcinoma with a focus of prostatic ductal carcinoma, organ confined (pT2) with negative margins (Figs. 1A, 1B). Initial postoperative PSA was undetectable, but in 1991, it became detectable and continued to increase to 0.8 in 1994. Bone scan and imaging of the pelvis were negative for metastatic disease. The patient received radiation therapy to his prostatic bed beginning July 1994 when the patient was 65 years old. His postradiation PSA was 0.8 and initially decreased, but in January 1997, it was 2.1. The patient denied any weight loss, fevers or chills, chest pain or shortness of breath, abdominal pain, bone pain, increased urinary frequency, urgency, or hesitancy, dysuria, or hematuria. He was having regular bowel movements. He was a lifetime nonsmoker. On examination, the patient was afebrile and his vital signs were stable. He was alert and generally appeared well. He had no cervical or axillary adenopathy. Lungs were clear to auscultation bilaterally. His abdomen was soft, nontender, and nondistended. He had a well-healed midline surgical scar. Rectal examination showed no palpable nodularity in the prostatic bed and good sphincter tone. Extremities were warm and well-perfused without edema, clubbing, or cyanosis. His laboratory test

Comparison of biochemical failure definitions for predicting local cancer recurrence following cryoablation of the prostate

Various definitions of biochemical failure (BF) have been used to predict cancer recurrence following prostate cryoablation. However to date, none of these definitions have been validated for this use. We have reviewed several definitions of BF to determine their accuracy in predicting biopsy-proven local recurrence following prostate cryoablation. The Columbia University Urologic Oncology Database was queried for patients who underwent prostate cryoablation between 1994 and 2010, and who subsequently underwent surveillance biopsy due to clinical suspicion of prostate cancer recurrence. Serial postoperative prostate-specific antigen (PSA) results were used to determine BF according to various definitions of BF. Biopsy results were used to determine local recurrence. Sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curve area were calculated for each of the BF definitions. A total of 110 patients met inclusion criteria for the study. These patients were treated with primary full-gland (n = 38), primary focal (n = 24), or salvage cryoablation (n = 48). On surveillance biopsy, 66 patients (60%) were found to have locally recurrent prostate cancer. The most accurate BF definition overall was PSA nadir plus 2 ng/ml (Phoenix definition), with sensitivity, specificity, and ROC curve area of 68%, 59%, and 0.64, respectively. Overall, the Phoenix definition best predicted local cancer recurrence following prostate cryoablation. These preliminary data may be useful for researchers evaluating the short-term efficacy of cryoablation, and for urologists assessing their patients for potential cancer recurrence.

Conformal Postoperative Radiotherapy in Patients With Positive Resection Margins and/or pT3-4 Prostate Adenocarcinoma

To evaluate outcome and toxicity of high-dose conformal radiotherapy (RT) after radical prostatectomy. Between August 1998 and December 2007, 182 consecutive patients with positive resection margins and/or pT3-4, node-negative prostate adenocarcinoma underwent postoperative conformal RT. The prescribed median dose to the prostate/seminal vesicle bed was 66.6 Gy (range 50-70). Hormone therapy (a luteinizing hormone-releasing hormone analogue and/or antiandrogen) was administered to 110/182 (60.5%) patients with high-risk features. Biochemical relapse was defined as an increase of more than 0.2 ng/mL over the lowest postoperative prostate-specific antigen (PSA) value measured on 3 occasions, each at least 2weeks apart. Median follow-up was 55.6 months (range 7.6-141.9 months). The 3- and 5-year probability of biochemical relapse-free survival were 87% and 81%, respectively. In univariate analysis, more advanced T stages, preoperative PSA values ≥10 ng/mL, and RT doses <70 Gy were significant factors for biochemical relapse. Pre-RT PSA values >0.2 ng/mL were significant for distant metastases. In multivariate analysis, risk factors for biochemical relapse were higher preoperative and pre-RT PSA values, hormone therapy for under 402 days and RT doses of <70 Gy. Higher pre-RT PSA values were the only independent predictor of distant metastases. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 72 (39.6%) and 91 (50%) patients, respectively. There were 2 cases of Grade III GI toxicity but no cases of Grade IV. Late GU and GI toxicities occurred in 28 (15.4%) and 14 (7.7%) patients, respectively: 11 cases of Grade III toxicity: 1 GI (anal stenosis) and 10 GU, all urethral strictures requiring endoscopic urethrotomy. Postoperative high-dose conformal RT in patients with high-risk features was associated with a low risk of biochemical relapse as well as minimal morbidity.

Selective Lymph Node Dissection for Castration-Resistant Prostate Cancer

Background: No relevant data have been published on the impact of retroperitoneal lymph node dissection (LND) on clinical outcome in patients with castration-resistant prostate cancer. Methods: We retrospectively studied the records of 6 patients with lymph node metastases from castration-resistant prostate cancer who underwent a retroperitoneal LND between 2005 and 2010. Complication rate and clinical outcome were examined. Results: Mean patient age was 69.2 (63–81) years. Primary therapy was radical prostatectomy, radiation therapy, or pelvic LND and androgen deprivation in 3, 2 and 1 cases, respectively. Mean prostate-specific antigen (PSA) at LND was 37.6 (20.3–139) ng/dl. LND was performed as a modified unilateral (n = 3), bilateral (n = 1) and bilateral extended (n = 2) approach with a median lymph node density of 0.739 (0.111–1). Preoperative Charlson index was 0 (n = 3) or 1 (n = 3). No intra- or postoperative complications occurred. The average postoperative decline of PSA was 39.3% (–99.4 to +31.3). Differences between mean pre- and postoperative PSA velocities and densities were 23.9 ng/ml/year and 11.2 months, respectively (p = 0.24 and p = 0.40). Four patients (67%) developed bone metastases after a mean period of 23.5 (5–58) months. Median bone metastases-free survival was 15.5 months and median overall survival after LND was 31.7 months on Kaplan-Meier analysis. Conclusions: A selective LND in castration-resistant prostate cancer patients could be safely performed. A positive effect on the PSA and PSA kinetics was accomplished for the majority of patients. This new surgical approach represents an alternative treatment option in the palliative setting of prostate cancer patients and could delay toxic systemic therapy up to 12 months.

Prostate Cancer Biochemical Recurrence Rates After Robotic-Assisted Laparoscopic Radical Prostatectomy

To determine prostate cancer biochemical recurrence rates with respect to surgical margin (SM) status for patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP). IRB-approved radical prostatectomy database was queried. Patients were stratified as low, intermediate, and high risk according to D'Amico's risk classification. Postoperative prostate-specific antigen (PSA) values were obtained every 3 mo for the first year, then biannually and annually thereafter. Biochemical recurrence was defined as ≥0.2ng/mL. Patients receiving adjuvant or salvage treatment were included. Positive surgical margin was defined as presence of cancer cells at inked resection margin in the final specimen. Margin presence (negative/positive), margin multiplicity (single/multiple), and margin length (≤ 3mm focal and >3mm extensive) were noted. Kaplan-Meier curves of biochemical recurrence-free survival (BRFS) as a function of SM were generated. Forward stepwise multivariate Cox regression was performed, with preoperative PSA, Gleason score, pathologic stage, prostate gland weight, and SM as covariates. At our institution, 1437 patients underwent RALP (2003-2009). Of these, 1159 had sufficient data and were included in our analysis. Mean follow-up was 16 mo. Kaplan-Meier curves demonstrated significant increase in BRFS in low-risk and intermediate-risk groups with negative SM. Overall BRFS at 5 y was 72%. Gleason score, pathologic stage, and SM status were significant prognostic factors in multivariate analysis. Negative surgical margins resulted in lower biochemical recurrence rates for low-risk and intermediate-risk groups. Multifocal and longer positive margins were associated with higher biochemical recurrence rates compared with unifocal and shorter positive margins. Documenting biochemical recurrence rates for RALP is important, because this treatment for localized prostate cancer is validated.

Robotic radical prostatectomy as the initial step in multimodal therapy for men with high‐risk localised prostate cancer: initial experience of 160 men

• To report the outcome of robotic-assisted laparoscopic radical prostatectomy (RALP) for men with localised high-risk prostate cancer at diagnosis. • Although commonly managed by radiotherapy (RT) with prolonged androgen-deprivation therapy (ADT), we hypothesize that initiation of multimodal therapy with RALP is oncologically efficacious and may allow many men to avoid ADT. • Between December 2003 and September 2010, 1480 men underwent RALP of whom 160 fulfilled the National Comprehensive Control Network criteria for high-risk disease (prostate-specific antigen (PSA) > 20 ng/mL and/or clinical stage, cT ≥ 3 and/or biopsy Gleason score ≥ 8). • Biochemical recurrence (postoperative PSA ≥ 0.2) was used to assess outcome after RALP monotherapy. • Treatment failure was defined as either a rising PSA level after salvage RT or the initiation of ADT. • The mean age ± standard deviation was 63.1 ± 6.3 years. Median PSA level was 9.95 ng/mL (interquartile range 6.0-21.4). • Analysis of prostatectomy specimen showed Gleason 8-10 cancers in 65 (41%), and extracapsular disease, pT ≥ 3, in 96 (60%) of which seminal vesicle invasion was evident in 36 (23%). Downgrading by prostatectomy occurred in 64 (40% of total group) and five (3%) were downstaged to pT2 disease. By contrast, any upgrading occurred in 29 (18% of total group) and upstaging occurred in 68 (43%). The overall positive surgical margin rate was 38%, correlating with stage pT2 (15%) or pT3 (53%). • With median follow-up of 26.2 months (interquartile range 5.5-37.3), two non-cancer-related deaths have occurred (overall survival 98.8%; cancer-specific survival 100%), and biochemical recurrence has occurred in 53 men (33%). RALP surgery has served as monotherapy (n= 117, 73%), or has been followed by salvage RT (n= 24, 15%) and/or ADT (n= 43, 27%). Overall 2-year and 3-year treatment failure was 31 and 41%, respectively. • Serum PSA level was the only independent predictor of overall treatment failure (hazard ratio [HR] 1.02, P= 0.001) although a strong trend was observed for both clinical stage (HR 1.22, P= 0.058) and the number of positive biopsy cores on transrectal biopsy (HR 1.06, P= 0.057). • RALP incorporating the use of postoperative RT is a good multimodal management strategy for men with this aggressive variant of prostate cancer. • At median follow-up in excess of 2 years, we found low rates of treatment failure enabling a high proportion of men to remain free of ADT.

Identifying Node-Positive Prostate Cancer Patients Who May Benefit From Adjuvant Pelvic Radiation Following Prostatectomy

Identifying Node-Positive Prostate Cancer Patients Who May Benefit From Adjuvant Pelvic Radiation Following Prostatectomy

Is There a Way to Predict Stress Urinary Incontinence After Holmium Laser Enucleation of the Prostate?

In this study we defined high risk patients at high risk of stress urinary incontinence after holmium laser enucleation of the prostate. We performed a retrospective analysis during a 10-year period of 949 consecutive patients treated with holmium laser enucleation of the prostate by a single surgeon. Patients were divided into group 1--those without postoperative stress urinary incontinence (902) and group 2--those with stress urinary incontinence (47). All preoperative, intraoperative and postoperative clinical variables were compared between the 2 groups. Patient age, preoperative and postoperative prostate specific antigen, preoperative medications, preoperative acute retention and duration of postoperative catheter time were not associated with postoperative stress urinary incontinence. The presence of diabetes mellitus was significantly associated with a higher incidence of stress urinary incontinence (p <0.001). Using medians of the whole cohort, prostate volume greater than 81 gm, operative time greater than 96 minutes and reduction in prostate specific antigen greater than 84% were significantly associated with stress urinary incontinence. On multivariate analysis prostate volume greater than 81 gm, the presence of diabetes mellitus and greater than 84% reduction in prostate specific antigen remained statistically significant. Holmium laser enucleation of the prostate results in stress urinary incontinence at a rate comparable to that of other surgical techniques for the treatment of benign prostatic hyperplasia. The presence of diabetes mellitus, large prostate volume and a greater reduction in postoperative prostate specific antigen remained statistically significant for the development of stress urinary incontinence. Patients with diabetes, especially those with a large prostate, should be encouraged to start Kegel exercises in the immediate postoperative period.

Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy?

• To evaluate the biochemical-failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI). • Between 1994 and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. • Exclusion criteria were: detectable postoperative prostate-specific antigen, lymph node metastases and follow-up <18 months. • Therefore, the study group included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26 received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant ADT combined with RT and 82 were monitored. The endpoint for this analysis was biochemical no evidence of disease (bNED). • Preoperative prostate-specific antigen level, specimen Gleason score, age, clinical stage, surgical margin status and adjuvant treatment were evaluated in a multivariable analysis with respect to bNED survival. • After a mean (range) follow-up of 60.3 (18-185) months, 88 (44.2%) patients had a biochemical relapse. • The estimated 5- and 7-year bNED survival were 32.6% and 25.9% for the observation group, 44.4% and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8% and 62.1% for the adjuvant ADT combined with RT group. • On multivariate analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent prognostic factor of biochemical relapse. • RP appeared to be insufficient as a single treatment for patients with SVI. • The findings of the present study suggest that adjuvant ADT combined with RT after RP for patients with SVI confers a substantial benefit on 5-year bNED survival.

Usefulness of postoperative nadir prostate-specific antigen value by ultrasensitive assay as a predictor of prostate-specific antigen relapse for pathological T3 or positive surgical margins after radical prostatectomy for prostate cancer

Our aim was to identify prognostic factors and examine the usefulness of postoperative nadir prostate-specific antigen (PSA) value obtained by ultrasensitive assay for prediction of PSA relapse in prostate cancer patients with pathological T3 (pT3) or positive surgical margins. We analyzed 102 patients who were pathological T2 with positive surgical margins or pT3 without pathological lymph node metastasis or neoadjuvant hormonal therapy. Patients were classified into three groups according to postoperative nadir PSA value: <0.01 ng/ml, ≥0.01 ng/ml but <0.02 ng/ml, and ≥0.02 but <0.10 ng/ml. PSA relapse-free rate was compared according to postoperative nadir PSA. Univariate and multivariate analyses with the Cox proportional hazards regression model identified prognostic factors for PSA relapse. Of the 102 patients, 22 (21.6%) developed PSA relapse within a median follow-up time of 31.3 months. PSA relapse-free rate at 30 months was 81.2%. Univariate and multivariate analyses revealed that postoperative nadir PSA was the only statistically significant risk factor: postoperative nadir PSA ≥0.01 ng/ml but <0.02 ng/ml (P = 0.009, HR: 4.502, 95% CI: 1.457-13.916); ≥0.02 ng/ml but <0.10 ng/ml (P < 0.001, HR: 15.126, 95% CI: 4.738-48.292). PSA relapse-free rates at 30 months in patients with postoperative nadir PSA <0.01 ng/ml, ≥0.01 ng/ml but <0.02 ng/ml, and ≥0.02 ng/ml but <0.10 ng/ml were 91.9, 57.1, and 20.0%, respectively. Postoperative nadir PSA value obtained by ultrasensitive assay was useful as a predictor of PSA relapse among patients with adverse pathological features. Patients with postoperative nadir PSA of <0.01 ng/ml may have low risk of PSA relapse.

Persistently elevated prostate-specific antigen at six weeks after radical prostatectomy helps in early identification of patients who are likely to recur

To determine the prognostic factors of biochemical recurrence in patients who failed to achieve an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) for prostate cancer. We reviewed data on 240 men who underwent RP as first-line treatment and who had a PSA assay available at 6 weeks after surgery. Persistent detectable PSA was defined as a PSA level ≥ 0.1 ng/ml at 6 weeks after surgery. Overall, 83 men presented persistently elevated PSA after RP and 81 had a biochemical recurrence. Median follow-up was 44 months. In univariate analysis, these factors were associated with biochemical recurrence: preoperative PSA level (P < 0.0001), biopsy and pathologic Gleason score (P < 0.001), capsular involvement (P = 0.0001), positive surgical margins (P < 0.0001), pathological stage ≥ T3 (P = 0.0001), and detectable post-operative PSA ≥ 0.1 ng/ml (P = 0.0001). In a multivariate analysis, only the detectable post-operative PSA level ≥ 0.1 ng/mL (P = 0.001), positive surgical margins (P = 0.002), and pathological stage ≥ T3 (P < 0.001) were significant. The individual, five-year, PSA-free survival rate for men with post-operative PSA <0.1 ng/ml and ≥ 0.1 ng/ml were 59 and 42%, respectively (P < 0.001). A majority of patients who failed to achieve an undetectable PSA after surgery had a subsequent biochemical recurrence in the outcome. A systematic PSA assay 6 weeks after RP could be useful to early identify patients who are likely to recur.

Dynamic prediction of metastases after radical prostatectomy for prostate cancer

What's known on the subject? and What does the study add? One of two problems plagues virtually are existing post-prostatectomy prediction tools: either (1) they predict PSA recurrences (which are of unclear importance) or (2) the predictions they make are anchored at the date of surgery and are not updated based on how patients evolve over the postoperative years. Our prediction tool is a significant improvement over existing prediction tools in that it predicts the development of metastases which is a very important clinical endpoint that indicates incurable prostate cancer. Additionally, our tool allows for updated predictions at any point following radical prostatectomy by considering commonly available postoperative information (postoperative serum PSA and use of adjuvant therapies) to modify its risk predictions. The net result is a dynamic tool that renders clinically relevant predictions that change as the patient's clinical status changes throughout the postoperative course. • To develop a dynamic algorithm that predicts the risk of metastases from any time point after radical prostatectomy (RP). • The study cohort consisted of 5741 RP patients who were treated from 1990-99. • Patients were grouped into one of four clinical states at follow-up: State(1) , prostate-specific antigen (PSA) undetectable; State(2), PSA 0.15-0.39 ng/mL; State(3), PSA ≥0.4 ng/mL; and State(4), previous androgen deprivation or radiation therapy. • Follow-up epochs (alive and at risk of systemic progression) at 0, 2, 4 and 6 years post-RP, cumulative incidence curves and multistate Cox models were used to assess the risk of metastases over the ensuing 5-year interval. • Gleason score, seminal vesicle and surgical margin involvement, and PSA variables were evaluated as predictors. • Median follow-up was 11.7 years, with 4411, 4256 and 3983 patients followed with PSA at 2, 4 and 6 years, respectively. • In total, 287 metastatic events occurred and the 5-year risk of metastasis was 0.4%, 2.1%, 8.7% and 12.6% for men in States 1, 2, 3 and 4, respectively. • Independent predictors of metastasis by group included seminal vesicle involvement (all groups), Gleason score (groups 1, 3 and 4), current PSA (groups 3 and 4) and maximum past PSA (group 4). • We present a web-based prognostic tool for patients undergoing RP that is valid at many time points after surgery. • Our tool predicts the development of metastases.

Incidental prostate cancer revisited: Early outcomes after holmium laser enucleation of the prostate

Incidental prostate cancer (PCa) after treatment of benign prostate hyperplasia (BPH) is becoming less common. This is a result of the changing patterns of BPH treatment. The purpose of the present research was to re-examine the clinical outcomes and importance of cT1a and cT1b PCa in a contemporary cohort after holmium laser enucleation of the prostate (HoLEP). All patients with newly diagnosed PCa after HoLEP were retrospectively identified. Pre- and postoperative prostate-specific antigen (PSA), biopsy history, pathological features and disease progression were examined. Patients were matched to a control group with benign pathology for outcome comparisons. The database consisted of 240 consecutive patients, aged 52-90 years with prostate sizes from 25 to 375 cm(3) . A total of 28 patients were identified with incidental PCa (14 cT1a and 14 cT1b). Median follow up was 11 months and 13 months for cT1a and cT1b, respectively. Hospitalization time, catheterization time, complications and functional outcomes were similar. Three patients with cT1b required additional treatment as a result of PSA progression. All other cancers are being closely followed. The functional benefits of HoLEP are well established. The incidental PCa detection rate of 11.7% shows the potential benefit of pathological analysis. Just 10.7% of these patients received additional treatment, but this might be significant as these patients would otherwise go untreated. The impact on disease-specific survival and progression requires a longer follow up.

Outcome After Conformal Salvage Radiotherapy in Patients With Rising Prostate-Specific Antigen Levels After Radical Prostatectomy

This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. After SRT, 66% of patients reached a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer-specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer-specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer-specific survival does not decrease rapidly.

Neoadjuvant trial of sunitinib malate and androgen ablation (ADT) in patients with localized prostate cancer (PCa) at high risk for recurrence.

143 Background: Presurgical ADT does not improve long-term outcomes in patients (pts) with high-risk localized PCa. Since the VEGF and PDGF signaling pathways have been implicated in PCa progression, and ADT results in endothelial cell apoptosis in the prostate by a VEGF-mediated mechanism, we hypothesized that combined treatment with sunitinib malate (SU), an oral inhibitor of the tyrosine kinases of VEGFR and PDGFR, might improve the efficacy of ADT in this pt population. Methods: Pts with no radiological evidence of metastases and either PCa ≥ clinical (c)T3 disease or Gleason grade 8-10 or serum prostate-specific antigen (PSA) ≥ 20 ng/mL or cT2b-c and Gleason 7 and PSA ≥10 ng/mL (AJCC, 1992), received i.m. leuprolide and oral SU for three 30-day cycles followed by surgery. SU was administered continuously at 37.5 mg daily (25 mg daily in the initial 6 pts). The primary endpoint of this phase II trial was rate of pathologic complete response (pCR). Secondary endpoints included safety and time to progression (TTP). Unresectable pelvic nodal disease, confirmed post-operative PSA ≥ 0.2 ng/mL, or administration of post-operative radiation or ADT, defined treatment failure. Results: Forty-four pts completed accrual, with a median age of 58 years (range 47-72); 34 Caucasian, 5 African-American, 4 Hispanic, and 1 Indian. High-risk criteria included cT3 (24/44), Gleason 8-10 (30/44), PSA ≥ 20 ng/mL (16/44). Two men were ineligible/declined therapy and one postponed surgery. No grade 4 toxicities or related discontinuations were observed. Thirty-five pts completed 3 months on 37.5 mg daily SU plus ADT and surgery with no unexpected complications. Of these, 2 pts experienced a pCR. Twenty (57%) pts have failed treatment or died, with a median TTP 27 months (95% CI: 12 – not estimable). The median follow-up of the remaining event-free pts is 35 months (range 23-41). Conclusions: The 3-months preoperative combination of SU and ADT is safe and well tolerated in pts with high-risk primary PCa. We observed 2 complete remissions in 35 patients. Ongoing characterization of molecular changes in the epithelial and stromal compartments will help understand the mechanisms of SU activity in PCa. [Table: see text]

Salvage Radical Prostatectomy Following Primary High Intensity Focused Ultrasound for Treatment of Prostate Cancer

High intensity focused ultrasound for the treatment of primary prostate cancer is increasing in a subset of men seeking definitive treatment with reduced morbidity. We review outcomes in men undergoing salvage radical prostatectomy after failed whole gland high intensity focused ultrasound. Prospective data were collected for men presenting with an increasing prostate specific antigen and biopsy proven prostate cancer after high intensity focused ultrasound from 2007 to 2010 who underwent salvage open radical prostatectomy with a 22-month median followup, including prostate specific antigen, prostate volume, pathology results, continence and erectile function. Data for 15 men were available, including median age 64 years (IQR 55-69), Gleason score before high intensity focused ultrasound of 6 (8), Gleason score 7 (7), median cores positive 39% (IQR 17%-63%) and median prostate specific antigen 7 ng/ml (IQR 5-8). Whole gland high intensity focused ultrasound achieved median nadir prostate specific antigen 1.1 ng/ml (IQR 0.5-3.1). Biopsy after high intensity focused ultrasound demonstrated Gleason score 6 (in 3 patients), 7 (9) and 8/9 (3), and 42% (IQR 25%-50%) cores positive and a median time from high intensity focused ultrasound to radical prostatectomy of 22 months (IQR 7-26). Perioperative morbidity was limited to 1 transfusion in a patient with a rectal injury. Pathologically extensive periprostatic fibrosis was found with persistent prostate cancer, as pT3 disease (in 9 of 14), Gleason scores 6 (2), 7 (9) and 8 of 9 (4), with focally positive margins in 3 of 11 (pT3a). Postoperative prostate specific antigen was unrecordable in 14 of 15 patients with further treatment in 2. Postoperative continence (more than 12 months of followup) yielded no pad use in 6 of 10 men with universally poor erectile function. Radical prostatectomy as salvage is feasible for men in whom high intensity focused ultrasound failed, but with a higher morbidity than for primary surgery. Pathology results are alarming given the number of cases with extraprostatic extension yet early followup data suggest acceptable oncologic control. These results should be factored in when counseling men who wish to undergo primary high intensity focused ultrasound.

バイポーラーシステムを利用した経尿道的前立腺核出術（Transurethral enucleation with bipolar：TUEB）の臨床的検討

Transurethral enucleation with bipolar (TUEB) is an established procedure for treating patients with benign prostatic hyperplasia (BPH). In this study, the usefulness of TUEB was evaluated by comparing the preoperative and postoperative results. A total of 45 patients with symptomatic BPH underwent TUEB at our hospital between February 2008 and August 2009. All the patients were assessed using the International prostate symptom score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), maximum urinary flow rate (Qmax), post void urine residue (PVR), serum prostate specific antigen (PSA) measurement, and estimated prostate weight. Total operative time, enucleation time, enucleated tissue weight, changes in levels of hemoglobin, hematocrit and serum sodium, duration of urethral catheterization, and complications were also investigated. IPSS, QOL index, Qmax, and PVR were reassessed 1, 3, 6 and 12 months after surgery. PSA reduction rate was also assessed 3 months after surgery. The average age was 71.6 years (60-84 years), estimated prostate weight 53.2 g (11.8-105.6 g), total operative time 125.5 minutes (76-212 min.), enucleation time 96.1 min (56-169 min), enucleated tissue weight 32.3 g (6-82 g), and duration of urethral catheterization 2.5 days (2-7 days). Blood transfusion was not required and hyponatremia was not observed in any patients. IPSS, QOL index, OABSS, PVR, and Qmax were significantly improved 1 month after surgery. As complications, re-catheterisation was reported in 2 patients (4.4%), bladder tanponade in 1 (2.2%), and urinary incontinence requiring at least 1 pad 6 months after surgery in 1 (5.9%). Postoperative PSA declined by 89.8% 3 months after surgery. TUEB was a safe and effective treatment procedure for patients with BPH.

Commentary on “Impact of postoperative prostate-specific antigen disease recurrence and the use of salvage therapy on the risk of death”. Choueiri TK, Chen MH, D'Amico AV, Sun L, Nguyen PL, Hayes JH, Robertson CN, Walther PJ, Polascik TJ, Albala DM, Moul JW, Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA: Cancer 2010;116:1887–92

Commentary on “Impact of postoperative prostate-specific antigen disease recurrence and the use of salvage therapy on the risk of death”. Choueiri TK, Chen MH, D'Amico AV, Sun L, Nguyen PL, Hayes JH, Robertson CN, Walther PJ, Polascik TJ, Albala DM, Moul JW, Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA: Cancer 2010;116:1887–92

Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer

• To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology-proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer. • This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1). • Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic-assisted) with bilateral pelvic dissection. • Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization. • Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8-month median follow-up, 11 patients were disease-free and three had persistent postoperative prostate-specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months. • Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6-month mean follow-up continued to need one or two pads per day. • Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery. • Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer-term data are required.