Persistent PSA Research Articles

Comparison in the follow-up of two patients with persistent elevated PSA and negative prostate biopsy

Purpose To compare two clinical cases on the follow-up of patients with benign prostatic hyperplasia at risck of progression, negative prostate biopsy and persistent elevated PSA levels. Materials After a first negative prostate biopsy for elevated PSA levels, Case A received dutasteride therapy for benign prostatic hyperplasia, whereas Case B continued his therapy without dutasteride. In both cases, other diagnostic procedures or other biopsies were decided on the basis of PSA level modifications. Results Case A showed a stabilization of PSA levels with a new nadir; the patient did not undergo new biopsies or other diagnostic procedures till the presence (24 months of follow-up) of a PSA elevation despite dutasteride therapy. A new biopsy, then, showed a prostate adenocarcinoma. Case B showed persistent and progressive PSA elevation; the patient underwent other diagnostic procedures and 2 new negative biopsies. Only after 26 months of follow-up a further biopsy showed a prostate adenocarcinoma. Conclusions 5-alpha-reductase inhibitors can reduce the number of unnecessary prostate biopsies.

Confronto Nel follow-up di Due Pazienti con Persistente Elevazione del PSA e Biopsia Prostatica Negativa

To compare two clinical cases on the follow-up of patients with benign prostatic hyperplasia at risck of progression, negative prostate biopsy and persistent elevated PSA levels. After a first negative prostate biopsy for elevated PSA levels, Case A received dutasteride therapy for benign prostatic hyperplasia, whereas Case B continued his therapy without dutasteride. In both cases, other diagnostic procedures or other biopsies were decided on the basis of PSA level modifications. Case A showed a stabilization of PSA levels with a new nadir; the patient did not undergo new biopsies or other diagnostic procedures till the presence (24 months of follow-up) of a PSA elevation despite dutasteride therapy. A new biopsy, then, showed a prostate adenocarcinoma. Case B showed persistent and progressive PSA elevation; the patient underwent other diagnostic procedures and 2 new negative biopsies. Only after 26 months of follow-up a further biopsy showed a prostate adenocarcinoma. 5-alpha-reductase inhibitors can reduce the number of unnecessary prostate biopsies.

Next-Generation Therapy for Residual Prostate Cancer

Prostate cancer claimed an estimated 136,500 lives globally in 2011. Ironically, the best existing treatment strategies provide survival benefits and missed opportunities to further improve outcomes. Prostatectomy provides the greatest survival benefit, albeit the risk of systemic recurrence increases dramatically with extracapsular involvement. To date, further systemic treatment is not generally prescribed for these 'high-risk' patients until such time as advanced disease is diagnosed based on persistent high PSA levels and/or when larger tumors are confirmed by imaging. This recurrent form of the disease is most often terminal. Androgen deprivation therapy (ADT) provides outstanding early control for these patients, which is rather tragic as the early benefits of ADT are lost within 2 years for most men, as the cancer again progresses to an incurable 'late-stage' castration-resistant form of the disease with a median survival of approximately 18 months. We review the potential of targeted α-therapy as an adjuvant with minimal side effects for early-stage high-risk patients to be administered immediately following prostatectomy and/or during ADT.

Prostatectomie radicale de sauvetage après échec de curiethérapie : étude préliminaire

Analysis of preliminary results in six patients operated by second-line (salvage) radical prostatectomy for local recurrence after low-dose brachytherapy. Since January 2009, six patients had an open salvage radical prostatectomy with a lymph node dissection and without neurovascular bundles preservation for a low-dose I125 brachytherapy failure. Local recurrence was confirmed by trans-rectal biopsy or TURP. All the patients had PSA increase or lower urinary tract symptoms. Bone scan and pelvis MRI were performed to detect a locally advanced disease, a lymph node involvement or the presence of bone metastasis. Pathology reports and PSA level at 1, 3, 6 and 12 months were analyzed. Salvage radical prostatectomy with lymph node dissection was performed in all patients without major complications. The PSA level was below 0.1 ng/mL in five out of six patients at 1 and 3 months. The only case of persistent PSA is treated by androgen deprivation in a pT3b N1 patient. Salvage radical prostatectomy after brachytherapy failure was feasible with a limited perioperative morbidity. This second-line curative treatment in a selected group of patients should be kept in mind. Our early results looked promising.

Does prolonged anti-inflammatory therapy reduce number of unnecessary repeat saturation prostate biopsy?

The effect of a prolonged oral anti-inflammatory therapy on PSA values in patients with persistent abnormal PSA values after negative prostate biopsy (PBx) was evaluated. From September 2011 to September 2012, 70 patients (medi- an age 62 years), with persistent abnormal PSA values after negative extended PBx, were given an herbal extract with anti-inflammatory activity for 3 months (Lenidase®; 1 tablet daily constituted of baicalina, bromelina and escina). All patients were submitted to prostate biopsy for: abnormal DRE; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA < 25% and < 20%, respectively. Three months after the end of anti-inflammato- ry therapy all patients were revaluated; indication for repeat saturation biopsy (SPBx) and detection rate for PCa were compared with those previously recorded in our Department using the same inclusions criteria for biopsy. Oral administration of Lenidase® was well tolerated and no side effects were observed; PSA values decreased in 54 (77.8%) out 70 patients with a median PSA reduction of 20.5% (from 8.8 to 7 ng/mL) and remained unchanged in 16 patients (22.2%); the repeat SPBx rate resulted significantly lower (22.8% vs 35.5%; p < 0.05) showing a superimposable detection rate for PCa (3 cases) in comparison with our previous data (18.7% vs 22%). In our preliminary data a prolonged oral anti-inflammatory therapy reduced PSA levels in patients with negative PBx and persistent suspicious for PCa decreasing the indication to perform repeat SPBx (about 30% of the cases).

Very distal apical prostate tumours: identification on multiparametric MRI at 3 Tesla

What's known on the subject? and What does the study add? MRI has been shown to improve prostate cancer detection rates. Pinto et al. (J Urol 2011; 86: 1281-5) reported their outcomes on 101 patients with low, moderate or high suspicion lesions on multiparametric MRI that were subsequently targeted via an MRI/ultrasound fusion biopsy platform. The prostate cancer detection rates were 27%, 66% and 89% respectively. Sciarra et al. (Clin Cancer Res 2010; 16: 1875-83) performed a prospective trial in 180 patients with prior negative biopsy and persistent PSA elevation. Patients were randomized to either MRI targeted biopsy followed by random 12-core TRUS biopsy vs random TRUS guided biopsy alone. Prostate cancer detection in the MRI targeted group was 45.5% vs 24.4% in the random group. Although MRI has been shown to improve prostate cancer detection rates, there has not previously been any work looking at the ability of MRI to detect prostate cancer localized to the very distal apex of the prostate. This is an important topic in that it might lead clinicians to counsel their patients in treatment decisions if it is felt that a treatment might not treat this section of the prostate well, e.g. high intensity focused ultrasound therapy that might spare the distal apex. • To describe an undescribed 'very distal' apical prostate cancer on multiparametric MRI (mpMRI) since apical prostate cancer can be difficult to detect in transrectal ultrasound guided biopsy and might therefore be missed in treatment decisions such as high intensity focused ultrasound or surgical therapy. • From January 2011 to December 2012 a total of 210 consecutive patients underwent 3 T mpMRI with endorectal coil followed by our previously described MRI/ultrasound image fused and directed TRUS biopsies. • Patients also underwent 12-core TRUS sextant biopsies. • The inclusion criteria required at least one distal apical prostate lesion visualized on mpMRI and targeted for biopsy. • A total of 38 men (median age 62 years, median PSA 7.68 ng/dL) were identified as having distal apical prostate cancer on mpMRI. • Thirteen patients (34%) had a prior diagnosis of cancer and were on active surveillance protocols while 25 (66%) did not. Of those patients, 21 (55%) had undergone a median of two prior negative biopsies. • Twenty-two patients (58%) were positive on biopsy for prostate cancer. On breakdown of patients who were positive, 17 (77%) were positive on TRUS random biopsies and 21 (95%) were positive on MRI targeted biopsies with the majority of patients having multifocal disease. • At the distal apical lesions of interest, 80% were positive on MRI targeted biopsy. In addition 33% of these patients were upgraded based on MRI targeted biopsy at the distal lesion. • Very distal apical prostate cancer can be accurately detected and sampled with mpMRI and subsequent MRI/ultrasound fusion biopsy. • This may aid clinicians and patients in decision making for therapeutic modalities.

1465 DOES SALVAGE RADIATION THERAPY CHANGE THE BIOLOGY OF RECURRENT PROSTATE CANCER BASED ON PSA DOUBLING TIMES? RESULTS FROM THE SEARCH DATABASE

You have accessJournal of UrologyProstate Cancer: Localized VII1 Apr 20121465 DOES SALVAGE RADIATION THERAPY CHANGE THE BIOLOGY OF RECURRENT PROSTATE CANCER BASED ON PSA DOUBLING TIMES? RESULTS FROM THE SEARCH DATABASE Roberto Muller, Joseph Presti, William Aronson, Martha Terris, Christopher Kane, Christopher Amling, and Stephen Freedland Roberto MullerRoberto Muller Durham, NC More articles by this author , Joseph PrestiJoseph Presti Stanford and Palo Alto, CA More articles by this author , William AronsonWilliam Aronson Los Angeles and West Los Angeles, CA More articles by this author , Martha TerrisMartha Terris Augusta, GA More articles by this author , Christopher KaneChristopher Kane San Diego, CA More articles by this author , Christopher AmlingChristopher Amling Portland, OR More articles by this author , and Stephen FreedlandStephen Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1986AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Salvage radiation therapy (SRT) offers a second opportunity for prostate cancer (PCa) control after biochemical recurrence (BCR) in men treated with radical prostatectomy (RP). Although some retrospective data suggest an overall survival benefit, we hypothesized that in men with radio-resistant tumors, SRT may indeed promote transformation to a more aggressive cancer due to radiation-induced mutations. To test this, we used PSA doubling time (PSADT) as a surrogate for cancer aggressiveness and compared PSADT before and after SRT in men who failed SRT. METHODS Of 287 men who underwent SRT in SEARCH database since 1988, we detected 78 with SRT failure defined as PSA ≥ 0.2 ng/mL above the post-SRT nadir. Of these, 44 had PSADT available before and after SRT, which was compared using Wilcoxon's paired test with men serving as their own controls. Correlation between PSADT pre- and post-SRT was also measured using a non-parametric test (Spearman's test). We tested predictors of PSADT change using multivariable logistic regression. RESULTS Baseline data are in Table 1. PSADT after BCR and after SRT were only weakly correlated (Spearman's rho=0.154; Fig. 1). There were no differences in PSADT before and after SRT (10.6 vs. 12.2 months; P=0.85; Table 2). However, in some individual cases large changes were observed. Only seminal vesicle invasion showed a trend towards an association with a shorter post-SRT PSADT relative to the pre-SRT PSADT (P=0.067). Table 1. Baseline Data of Patients that Failed SRT and have PSADT Available After BCR and SRT Failure Characteristic Final population (n=44) Age at surgery, yrs. Median (IQR) 62.5(59-65) Range 50-75 PSA before surgery, ng/mL Median (IQR) 10.6(7.0-27.2) Range 1.5-70.9 PSA before SRT, ng/mL Median (IQR) 1.1(0.6-1.9) Range 0.1-9.3 Pathological Gleason score, no. (%) 2-6 13(29.6) 7 21(47.7) 8-10 10(22.7) Extracapsular extension, no. (%) 19(43.2) Positive surgical margins, no. (%) 23(52.3) Seminal vesicle invasion, no. (%) 15(34.1) Positive lymph nodes, no. (%) 1(2.3) Persistent detectable PSA nadir after surgery⁎, no. (%) 26(59.1) Radiation dosage⁎⁎, cGy Median (IQR) 6600(6600-6660) Range 6120-7200 ⁎ Defined as PSA nadir within 6 months of surgery ≥0.03 ng/mL; ⁎⁎ dosage available only in 24 patients. Table 2. Comparison Between PSADT After BCR and SRT failure and Characteristics of the Pool of PSA Samples Used for PSADT Calculation After BCR (n=44) After SRT failure (n=44) P⁎ PSADT, months .85 Median (IQR) 10.6(6.7-24.5) 12.2(7.9-21.6) Range 2.4-100 1.5-100 Interval between consecutive samples, days .87 Median (IQR) 120.1(71.0-171.3) 123.3(90.5-171.8) Range 44.0-403.0 46.4-340.0 Number of samples .02 Mean (SD) 4.3(2.2) 5.3(2.5) Range 2-11 2-15 Length of time between first and last PSA value, months .0093 Median (IQR) 12.3(5.2-19.4) 18.6(14.6-22.4) Range 3.0-23.9 3.0-23.9 ⁎ Wilcoxon's test for paired samples. CONCLUSIONS Overall, the PSADT after and before SRT were statistically identical suggesting that after SRT failure, PCa does not emerge with more aggressive biologic features. Further studies are needed to identify predictors and the clinical relevance of individual PSADT changes noted in our study. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e594 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roberto Muller Durham, NC More articles by this author Joseph Presti Stanford and Palo Alto, CA More articles by this author William Aronson Los Angeles and West Los Angeles, CA More articles by this author Martha Terris Augusta, GA More articles by this author Christopher Kane San Diego, CA More articles by this author Christopher Amling Portland, OR More articles by this author Stephen Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Diagnosis Of Prostate Cancer In Patients With Persistently Elevated PSA And Tumor-Negative Biopsy in Ambulatory Care: Performance of MR Imaging in a Multi-Reader Environment

False-negative results are obtained in approx. 20 % of prostate cancer (PCa) patients (pts) at initial systematic transrectal biopsy (Bx), in particular when digital rectal examination (DRE) or transrectal ultrasound (TRUS) is negative. The aim of this study was to assess whether MR endorectal imaging of the prostate in a multi-reader ambulatory care setting may assist in patient selection for re-biopsy. 115 consecutive pts with persistent PSA elevation, negative Bx, DRE and TRUS were examined using T2w axial and coronal and T1w axial sequences for tumor diagnosis. MR images were prospectively read as tumor-suspicious or tumor-negative by the MR radiologist on duty. Additionally, a retrospective readout of a prostate MR expert and an abdominal imaging fellowship-trained radiologist was performed to evaluate the effect of the reader's experience on tumor detection. Imaging findings were compared to the results of the repeat Bx (61 pts) or the clinical course of at least two years. For the prospective reading, the sensitivity of MRI was 83 %, the specificity was 69 %, the PPV was 33 % and the NPV was 96 %. ROC analysis revealed a significantly better performance of the prostate MR imaging expert compared to the abdominal imaging radiologist (area under ROC 0.88 vs. 0.66, p < 0.001). Based on the prospective reading, a pre-test probability for PCa of 17.4 % as in our study can be reduced to 5 % when obtaining a tumor-negative result in MRI. MR imaging in a multi-reader ambulatory care setting assists in patient selection for re-biopsy. Reducing the post-test probability for PCa to 5 % allows for further follow-up instead of re-biopsy in MR tumor-negative patients. Specific training and experience improve tumor detection in prostate MR imaging.

Salvage radiotherapy in patients with persisting/rising PSA after radical prostatectomy for prostate cancer

Radical prostatectomy (RP) and radiation therapy (RT) are two of the existing first-line therapeutic options for patients with prostate cancer, with best results achieved in patients with organ-confined disease. There are clearly defined risk factors predicting the outcome after RP (i.e., Gleason score, prostate-specific antigen [PSA] level before surgery, tumour stage, infiltration of the seminal vesicles or positive surgical margins) [1–4]. However, progression of the disease is a common event even in patients with good prognostic factors. Monitoring PSA levels is a sensitive means of assessing the result of RP for prostate cancer. Following RP, the PSA should become undetectable within 4 to 6 weeks, because the serum half-life of PSA is approximately 2 to 3 days [5]. Therefore, persistent serum PSA levels after RP indicate residual prostatic tissue, be it malignant disease or benign prostatic hyperplasia (BPH). In the former case such levels predate clinically evident disease and do correlate well with disease progression. A PSA increase of 0.2 ng/mL is a common definition of progression of the disease following RP. It occurs in up to 50% of patients with pT3 tumours and this value ranges up to 70% in case of pT3 tumours with positive surgical margins [6,7]. Using biopsies from the urethrovesical anastomosis, vital tumour tissue was found by different examiners in 35−55% of all patients with PSA elevation after RP without clinical findings suggestive of recurrent tumour [8–10].

Tolerability of ongoing phase II study of concomitant radiation and docetaxel followed by docetaxel in prostate cancer patients with a persistent or rising PSA after radical prostatectomy

e16054 Background: Patients with a detectable PSA after radical prostatectomy (RRP) have persistent disease and inevitably succumb to disease as progression ensues. Radiation has been used in the salvage setting, but has only been found to cure less than half of these patients. SWOG 8794 has recently reported a significant increase in metastasis free survival in 15 years with adjuvant radiation for patients with high risk findings after RRP. It is of particular interest if adjuvant chemoradiation (CRT) can improve the rate of reaching a PSA nadir of zero after RRP in men with persistent or rising PSA. This ongoing IRB approved trial has thus far evaluated the tolerability of CRT utilizing the radiosensitizing agent Docetaxel (DX) for 7 weeks after RRP followed by adjuvant full dose DX (75mg/m2). Methods: Patients: Chemotherapy/hormone naïve, status post RRP, post-op PSA &gt; 0.2 ng/mL on two separate occasions, ECOG ≤ 2; treated with taxane-based chemotherapy (DX 20mg/m2 weekly) concurrent with standard dose radiation for 7 weeks, and post-radiation chemotherapy DX (75mg/ m2) given every 21 days for 4 cycles with premedication intravenous dexamethasone. Primary endpoint: Rate of PSA decline; Number of subjects reaching PSA nadir of zero. Secondary endpoints: Progression Free Survival (PFS) based on PSA progression, toxicity graded via Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE), and overall survival (OS). Results: From 5/07 to 12/08, 16 pts with detectable PSA after RRP were treated; Median age 65 [48–74]; 16/16 completed CRT; 11/16 completed CRT and adjuvant DX; 3/16 dropped out due to adverse events after CRT; Toxicity: 19% (3/16) patients experienced Grade 3 toxicity during CRT and adjuvant DX; 29% (4/14) patients had Grade 3 toxicity during adjuvant DX; no Grade 4 toxicities. See Table . Conclusions: DX in combination with standard radiation appears to be well tolerated in patients with persistent PSA after RRP. [Table: see text] No significant financial relationships to disclose.

PT3R1-Prostatakarzinom

Approximately 50-60% of patients with tumor stage pT3R1 after radical prostatectomy (RP) who do not receive adjuvant therapy develop biochemical progression. At present it is unclear whether these patients should undergo immediate adjuvant irradiation or whether a wait and see approach should be adopted while monitoring PSA until the PSA level rises from zero and then initiate salvage radiotherapy (SRT).Three randomized trials showed that an absolute improvement of 20% in the 5-year biochemical no evidence of disease (bNED) could be achieved by administering adjuvant radiotherapy with 60 Gy in patients with tumor stage pT3R1, even with a PSA level around zero after RP. The rate of serious late effects is low. On the other hand, there are numerous, albeit retrospective studies, which provide evidence that SRT after an increase in PSA above zero is an effective treatment, but with higher total doses of 66-70 Gy and a higher rate of late effects. Prognostic factors such as the PSA level before radiotherapy is started, PSA doubling time, R1 resection, PSA velocity, and the Gleason score have a significant impact on both the return of the PSA level to zero and the bNED. Depending on the risk factor, between 20 and 70% of patients again achieve PSA levels around zero after SRT. Retrospective comparative studies suggest a benefit of adjuvant radiotherapy; prospective randomized trials do not exist.Adjuvant radiotherapy after RP in stage pT3R1 tumor and SRT in cases of PSA rising above zero or persistent PSA levels are valid options for the management of high-risk patients after RP. SRT requires higher total doses and thus carries a higher risk of late complications. A benefit has been demonstrated for bNED, but not for survival. The approach should be discussed with the individual patient.

Post prostatectomy multimodality adjuvant therapy for patients at high risk for prostate cancer relapse

16053 Background: Adjuvant systemic therapy improves survival for many loco-regional cancers, but few data describe adjuvant therapy of prostate cancer. We have conducted a pilot study of multimodality adjuvant therapy (MAT) following radical prostatectomy (RP) in subjects at high risk subjects for disease recurrence. Therapy was modeled after current adjuvant treatment of breast cancer, and included both adjuvant combination chemotherapy and prolonged androgen ablation. Methods: Subjects with high-risk CaP (predicted five year relapse risk >25% by 1999 Kattan post-op nomogram and/or persistent PSA after surgery) were offered MAT. Therapy included 6 cycles of combination chemotherapy Q 3wks (docetaxel [=doc] 70 mg/m2, estramustine 280 mg TID × 5 d, or doc 70 mg/m2, carboplatin AUC5), followed by 5 yr of androgen deprivation (leuprolide plus bicalutamide). Subjects with pT4 Dz or multiple positive margins were also offered adjuvant radiation therapy following chemotherapy. Results: Twenty-eight high-risk subjects received MAT. Rx started an average of 78 d after RP. Clinical parameters include: mean age 59.9 yr; Gleason 8–10 64%; pT3b/4 57.1%; N1 70.3%, positive margins 57.1%. Mean predicted relapse risk (Kattan) was 63.6% (2 yr) and 76.4% (5 yr). Ave. chemo cycles = 5.8. Twenty subjects received doc/estramustine, and eight received doc/carboplatin. 7/28 received XRT as part of therapy. Maximum followup is 76.6 mos, ave. followup is 31 mos from RP. There have been no biochemical (PSA) relapses and 26/28 (93%) remain free of disease progression. 2/28 (7%) subjects relapsed clinically, without an elevated PSA at relapse, and both died of cancer. Major chemo toxicities are Gr3–4 neutropenia (65%), edema (30%), DVT (25% with doc/estramustine). Conclusions: Adjuvant MAT is tolerated by high-risk subjects. Biochemical or clinical failures in subjects treated with MAT are uncommon within this followup period; however, disease relapse in these subjects is aggressive and fatal. Doc/estramustine has an excessive risk of DVT, even with prophylactic coumadin. Doc/carboplatin has little risk of DVT and is our current chemotherapy choice in the adjuvant setting. PSA may be inadequate as the sole method to monitor high risk subjects treated with these adjuvant therapies. No significant financial relationships to disclose.

The value of 18F-Choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer

Patients with persistent elevated PSA and repeated negative prostate biopsy, that means having the prostate biopsied at multiple times, were investigated with 18F-choline PET/CT to delineate prostate cancer and guide renewed prostate biopsy. Twenty patients with elevated PSA and negative prostate biopsies underwent 18F-choline PET/CT. We performed an early examination of the pelvic region 3-5 min after application. After 30 minutes a whole body PET/CT examination was performed. Image analysis was performed visually and by semi-quantitative analysis calculating the maximum standardised uptake value (SUVmax). 18F-choline uptake was defined as focal, multifocal or inhomogeneous. After the 18F-choline PET/CT, all patients underwent a repeated prostate biopsy, and in the cases where a focal or multifocal uptake was found, the biopsy was guided by the result of the examination. Qualitative image analysis revealed focal 18F-choline uptake in 13 out of 20 patients. In five patients, prostate cancer was revealed by repeated aspiration biopsy. None of the patients with a multifocal or inhomogeneous 18F-choline uptake had a malignant neoplasm in the prostate. Semiquantitative analysis performed with SUVmax was not helpful in the discrimination of malignancy but showed high values also in benign prostate diseases, as well as in normal prostate tissue. The dual-phase protocol delivered no clear benefit in discriminating malignancy from benign alterations. The use of 18F-choline cannot be generally recommended for localising prostate cancer; however, in highly selected patients, we found useful additional information. In 25% of patients, 18F-choline PET/CT allowed the identification of neoplastic prostatic zones.

Phase I-II trial of weekly bicalutamide in men with high PSA and negative biopsy

1500 Background: Men with persistent PSA elevation after non-cancer findings are at high risk of prostate cancer (PC). Bicalutamide (Bic) is an androgen receptor antagonist, which, unlike finasteride, is not associated with testosterone (T) escape. Given its long half-life (6–8 days), allowing for a weekly administration with potentially reduced side effects, Bic may be a suitable chemopreventive agent. We assessed the activity and safety of a weekly low-dose Bic in a phase I-II study in subjects with PSA &gt;4 ng/ml and no PC at initial biopsies (10- 12 cores). Methods: Eligible subjects were sequentially assigned to either Bic 50 mg/week (group A), or 100 mg/week (group B), or no treatment (group C) for 6 mos. The outcome measures were the 6 mos changes in tissue Ki67 (primary endpoint), topoisomerase-IIa, Bcl- 2, and COX-2 by IHC, morphology and circulating PSA, prostatic acid phosphatase (PAP) and hormones. Results: From May, 2004 to June, 2006, 107 subjects were screened and 80 were enrolled: 26 in group A, 28 in group B, and 26 in group C. High-grade (HG) PIN decreased from 32% to 23% in the treated group and increased from 24% to 34% in controls; proliferative inflammatory atrophia (PIA) decreased from 41% to 32% in the treated group and increased from 14% to 19% in the controls. Complete remission of HG-PIN was found in 10/14 treated subjects versus 1/5 controls. Cancer or HG-PIN were found in 11 control subjects (52%) versus 16 subjects (36%) in the treated arms at 6 mos. Ki67 expression was significantly higher in HG-PIN lesions than in normal tissue (12% vs. 3%, p&lt;0.01), but it was not modulated by Bic. Bcl-2 expression in normal tissue was 0/1+ in most subjects, and increased in 36% of treated subjects versus 20% of controls. Total and free PSA, as well as PAP, decreased by &gt;30% on Bic. T, LH, estradiol and SHBG increased on Bic by 50–60%. There was no dose-related modulation in any biomarker. Treatment was well tolerated, mild (G1) breast pain and gynecomastia being recorded in 40% of treated subjects. Conclusions: Weekly Bic is active and safe in subjects with high PSA and negative biopsy. It seems to be associated with HG- PIN remission, Bcl-2 overexpression and a favorable modulation of PSA. The dose of 50 mg/week should be selected for future chemoprevention trials. No significant financial relationships to disclose.

Cáncer de próstata: nuevas técnicas diagnósticas. Estado actual de la biopsia de próstata

Ultrasound guided prostate biopsy is the only method to obtain the confirmation diagnosis of prostate cancer. Since its introduction at the end of the '80s multiple modifications of the technique have been implemented to improve cancer detection rates and to diminish the rate of false negative results, with maximum patient comfort and less complications. Bibliographic review and critical analysis of the literature on prostate biopsy. Published studies suggest extensive biopsy schemes increase detection rates in comparison to sextant biopsies, both first and successive biopsies, being necessary to sample the most lateral areas of the gland and the dorsal apex where the diagnostic yield is greater. The indications for repeated biopsies after a negative one include high grade PIN and/or Atypical Small Acinar Proliferation (ASAP), persistent PSA elevation and/or total PSA doubling time increase. There is no consensus about the time for repeating biopsies, although it seems that cancer detection rates descend after the third biopsy. The introduction of periprostatic anesthetic blockage techniques has enabled pain control, mainly in more extensive biopsies.

Undetectable PSA level following prostate brachytherapy

14609 Background: Following radical prostatectomy for adenocarcinoma of the prostate, a long term undetectable PSA level is associated with cure. Patients with persistent long term detectable but low PSA levels after prostate radiation are frequently thought to be cured with the assumption that residual benign prostate tissue may produce low levels of PSA in the absence of cancer. There is not an established PSA nadir following radiation therapy that is universally associated with cure. In our institutional experience PSA nadirs of less than or equal to (≤) 0.2 and ≤ .5 have been associated with disease control by the ASTRO consensus statement in 95% and 89% of patients respectively. None of our patients who have obtained an undetectable PSA following prostate brachytherapy have subsequently gone on to have a rising PSA. The purpose of this study is to determine the frequency of undetectable PSA following prostate brachytherapy. Methods: 209 consecutive patients were treated with radioactive Iodine 125 seed implantation alone as definitive treatment between 1/96 and 1/03. No patients received external radiation therapy or hormone therapy. Post treatment PSA levels were reviewed to ascertain the number of patients achieving undetectable PSA levels, PSA of ≤ 0.2, PSA ≤ 0.5, and PSA failure based on the ASTRO consensus statement definition. Results: At a median follow up of 80 months (range 36 to 120), 75 patients (36%) have achieved and maintained an undetectable PSA level. 27 patients (13%) have experienced biochemical failure by the ASTRO definition. 72% and 78% have achieved and maintained PSA nadirs of ≤ 0.2 and ≤ 0.5 respectively. Conclusions: There has been difficulty in comparing treatment results in patients treated with radical prostatectomy compared to radiation therapy for cancer of the prostate due to the different PSA patterns following the different treatments and the varying definitions of success or failure. Undetectable PSA level after prostate brachytherapy appears in our experience to be consistently associated with disease free status based on the most stringent definition of disease free status following prostatectomy. No significant financial relationships to disclose.

Weekly docetaxel and estramustine monophosphate (EMP) in the treatment of patients with prostate cancer and persistent/recurrent PSA elevation following primary therapy: A phase II trial of the Minnie Pearl Cancer Research Network

4759 Background: Treatment with docetaxel/EMP combinations has improved response rates in patients (pts) with hormone-refractory prostate cancer. Since a rising serum PSA level reliably detects subclinical metastases, we evaluated the feasibility, efficacy, and toxicity of weekly docetaxel and estramustine in pts with persistent or recurrent PSA elevations following primary therapy. Methods: In this phase II trial, we administered a treatment with docetaxel (35mg/m2 IV weeks 1, 2, 3) and EMP (140mg PO q 8 hours for 7 doses, beginning the evening prior to docetaxel, weeks 1, 2, 3); courses repeated every 4 weeks for 6 cycles. Eligible pts had persistent PSA elevation after primary local therapy, or rising PSA levels (without detectable metastases) following PSA normalization with primary therapy. Other eligibility criteria: ECOG PS 0–2; no previous chemotherapy; adequate organ function; informed consent. Results: Between 3/01 and 6/03, 30 pts entered this trial. Patient characteristics: median age 62 years; ECOG PS 0/1/2, 22/8/0; primary therapy: prostatectomy 12 pts (40%), prostatectomy/RT 10 pts (33%), RT alone 6 pts (20%), hormonal therapy only 2 pts (7%). 15 pts had received previous hormonal therapy. Pts received a median of 6 treatment courses (range 1 to 8). 28 of 29 evaluable pts (97%) had ≥ 75% decrease in PSA (CR 24 pts; PR 4 pts). After median follow-up of 21 months, the median, 1-year, and 2-year PFS are 14 months, 72% and 36%, respectively; 2-year overall survival is 91%. 15 pts (50%) remain in remission. Toxicity was moderate, with the following grade 3/4 toxicities: nail toxicity 3%, neutropenia 3%, fatigue 6%, N/V 10%, mucositis 3%. There were no treatment-related deaths, and no pt discontinued treatment due to toxicity. Conclusions: Treatment with weekly docetaxel/EMP produces a high PSA CR rate and is well tolerated in pts with early relapse of prostate cancer. Further evaluation of this regimen in early relapse and in the adjuvant setting is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Aventis

Salvage radiotherapy for rising or persistent PSA after radical prostatectomy

Salvage radiotherapy for rising or persistent PSA after radical prostatectomy

Hormonal therapy for patients with advanced adenocarcinoma of the prostate: is there a role for discontinuing treatment after prolonged androgen suppression?

Objectives To determine the hormonal (luteinizing hormone [LH], testosterone) and biochemical (prostate-specific antigen [PSA]) response to withdrawal of LH-releasing hormone (LHRH) agonist therapy for patients with prostate cancer with an undetectable PSA who received this treatment for an extended period. Methods Four selected patients older than 70 years of age with advanced adenocarcinoma of the prostate who were treated with a depot injection of LHRH and antiandrogen therapy had their treatment discontinued. During the period of total androgen blockade, each patient obtained and maintained a persistent undetectable PSA level. After cessation of androgen blockade, patients underwent serum measurements of PSA and testosterone at baseline and then every 6 months for 36 months. Serum LH was performed at baseline and then at 6, 18, and 36 months. Results At the time androgen ablative therapy was discontinued, patients had received LHRH agonist/antiandrogen therapy for a mean of 108 months (range 94 to 120). All 4 patients had castrate levels of testosterone (less than 0.5 ng/mL) and undetectable levels of PSA at baseline and with continued monitoring. At 6 and 18 months, all patients except one had LH levels in the normal range. All 4 patients remained clinically asymptomatic throughout the follow-up period with undetectable PSA levels. Conclusions Withdrawing hormonal therapy in asymptomatic patients with advanced prostate cancer after prolonged total androgen blockade was noted to be safe and effective in elderly patients who had achieved an undetectable PSA level. It appears that reduced testosterone levels may be a result of altered and potentially irreversible Leydig cell function rather than continued suppression of the hypothalamic-pituitary-testicular axis.

Results of Salvage Radiotherapy for Rising or Persistent PSA Following Radical Prostatectomy

Results of Salvage Radiotherapy for Rising or Persistent PSA Following Radical Prostatectomy