Undetectable Prostate-specific Antigen Level Research Articles

The treatment landscape of nonmetastatic castrate resistant prostate cancer: A contemporary perspective

ObjectivesThe incidence of nonmetastatic castrate resistant prostate cancer (nmCRPC) is not well defined in contemporary practice. The aim of this study is to describe the incidence and patterns of treatment of nmCRPC over the last 6 years at a single high-volume Australian health institution. Subjects and methodsAll men newly diagnosed with prostate cancer at Western Health, Melbourne from January 2016 to December 2021 were included in the study. Those diagnosed with nonmetastatic prostate cancer and treated with medical or surgical castration for biochemical failure post attempted curative therapy were retrospectively reviewed for signs of castration resistance using prostate specific antigen (PSA) and testosterone biochemical markers up until October 2022. ResultsFrom January 2016 to December 2021, 822 patients were diagnosed with prostate cancer, 590 had localized disease, 373 underwent definitive locoregional therapy, and 31 went on to have biochemical recurrence and were commenced on androgen deprivation therapy. Twenty-five patients had undetectable PSA levels and were classified as having nonmetastatic castrate sensitive prostate cancer (nmCSPC), whilst the remaining 6 patients experienced a rising PSA and were thus classified as nmCRPC. The incidence rate of nmCRPC was 228 cases per 100,000 person-years.The median age at the time of prostate biopsy was 74 years (interquartile range [IQR] 64–79) in the nmCRPC group and 62 years (IQR 57–69) in the nmCSPC group. The median prebiopsy PSA (ng/ml) in the nmCRPC and nmCSPC groups were 27.5 (IQR 19.9–50.4), and 16.5 (IQR 9.0–26.0), respectively. The median duration from prostate cancer diagnosis to onset of nmCRPC was 24 months (IQR 17–29) and the median PSA doubling time was 3.4 months (IQR 2.2–5.7). ConclusionsThus, nmCRPC is an uncommon disease. Further population-based studies are required to better understand the incidence of nmCRPC.

Low PSA radiographic disease progression on C11-choline PET.

For men with prostate cancer, radiographic progression may occur without a concordant rise in prostate-specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C-11 choline positron emission tomography (PET) imaging in patients achieving ultra-low PSA values and to evaluate clinical outcomes in this patient population. In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C-11 choline PET scan while the PSA value was less than 0.5ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan-Meier method. Intergroup differences were assessed using the log-rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP. A total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7-106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration-resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small-cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow-up of 49.4 (21.3-95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log-rank) as compared with other sites of rDP. Men with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

Comparison of senhance and da vinci robotic radical prostatectomy: short-term outcomes, learning curve, and cost analysis.

The Senhance® Robotic System is a new laparoscopy-based platform that has been increasingly used in radical prostatectomy (RP) procedures. The purpose of this study is to compare the outcome of Senhance RP (SRP) with da Vinci RP (DRP) cases. From August 2019 to April 2022, we prospectively recruited 63 cases of SRP. We compared the perioperative data, postoperative complication rates, short-term surgical outcomes (3-month postoperative undetectable prostate-specific antigen (PSA) and incontinence rates), learning curves, and cost analysis with data from 63 matched da Vinci Xi RP cases. There was no difference in BL (180 versus 180 ml, p = 0.86) and postoperative surgical complication rate (Clavient -Dindo grade I-IV, 25.3 versus 22.2%, p = 0.21) between the SRP cases and the DRP. Regarding the oncologic and continence function, there was no difference between positive margin rate (36.5% versus 41.3%, p = 0.58), rate of undetectable PSA level at postoperative 3 months (68.3 versus 66.7%, p = 0.85), and incontinence rate (14.3 versus 15.9%, p = 1.0) at postoperative 3 months between the two cohorts. The learning curve showed a quick downward slope for laparoscopic experienced surgeons. The median pocket cost for SRP patients in our hospital was $4170, which was lower than $7675 for the DRP patients. Safety and short-term outcomes are comparable between SRP and DRP. For experienced LRP surgeons, using the Senhance system to perform RP is straightforward. With a more affordable price as its biggest advantage, the Senhance system may serve as a safe and effective alternative for robotic RP.

Incidental Tc-99m MDP Uptake in Cortical-subcortical Parietotemporal Cerebral Area in a Patient with a History of Recent Ischemic Cerebrovascular Event who Underwent Whole-body Bone Scan.

The authors present Tc-99m methylene diphosphonate (MDP) uptake in the right parietotemporal area at whole-body bone scan (WBBS) in 75 years male patient with prostate adenocarcinoma Gleason score 3+4 (pT2N0Mx). No residual or metastatic disease was detected in the patient's Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography four months before WBBS. The patient had undetectable prostate-specific antigen levels and underwent WBBS to restage prostate cancer due to equivocal findings in previous WBBS. Current WBBS planar views revealed heterogeneous Tc-99m MDP uptake in the right parietotemporal area and the sphenoid bone in addition to equivocal uptake on the lower lumbar vertebrae. Single-photon emission computed tomography study to identify the MDP-avid lesion on the right cranial area revealed heterogeneous Tc-99m MDP uptake in the right parietotemporal area and sphenoid bone. The patient had a history of transsphenoidal surgery for a hypophyseal tumor two years ago and a recent cerebrovascular event (CVE). Diffusion-weighted magnetic resonance imaging revealed a cortical-subcortical patchy area of restricted diffusion in the parietotemporal region compatible with acute ischemia. Heterogeneous Tc-99m MDP uptake in the right parietotemporal area was attributed to recent CVE and secondary vascular-tissue change-related dystrophic calcification.

Association of prostate-specific antigen (PSA) response and overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 3 ARASENS trial.

5078 Background: Reductions in PSA level have been associated with improved OS in patients (pts) with mHSPC. In ARASENS (NCT02799602), darolutamide (DARO) + androgen-deprivation therapy (ADT) in combination with docetaxel significantly reduced the risk of death by 32.5% (hazard ratio [HR] 0.675; 95% confidence interval [CI] 0.568–0.801; P&lt; 0.0001) vs ADT + docetaxel in pts with mHSPC. We report the association between PSA response and OS from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or matching PBO + ADT and docetaxel. Serum PSA was measured at screening and every 12 weeks. Exploratory analyses included time to PSA progression (≥25% increase from PSA nadir [lowest or at study entry] and PSA increase ≥2 ng/mL ≥12 weeks from nadir [both confirmed by a second value ≥3 weeks later]) and undetectable PSA (&lt; 0.2 ng/mL for 2 samples ≥3 weeks apart) at 24, 36, and 52 weeks and any time during treatment. Comparisons between treatment groups were performed using the Cochran-Mantel Haenszel test stratified by randomization stratification factors (metastatic spread according to TNM classification and alkaline phosphatase levels at study entry). Post hoc landmark analyses evaluated the association between undetectable PSA at weeks 24 and 36 and OS for the overall population. Results: Of 1306 randomized pts, 1305 were included in the full analysis set (DARO 651; PBO 654), both with ADT and docetaxel. Median (range) PSA levels at study entry were 30.3 (0.0–9219.0) and 24.2 (0.0–11,947.0) ng/mL, respectively. DARO significantly prolonged time to PSA progression (HR 0.255; 95% CI 0.208–0.313; P&lt; 0.0001). Undetectable PSA was achieved in more pts receiving DARO (48.7%) vs PBO (23.9%) at 24 weeks, and the rate continued to increase at 36 and 52 weeks in the DARO group to 57.1% and 60.2%, respectively, vs minimal change in the PBO group (25.1% and 26.1%). Undetectable PSA levels at any time were achieved in 67.3% in the DARO group and 28.6% in the PBO group. A treatment difference in undetectable PSA based on non-overlapping 95% CIs was observed at all time points. For the overall population, OS was improved for pts who achieved undetectable PSA levels vs those who did not at 24 weeks (HR 0.398; 95% CI 0.321–0.493) and 36 weeks (HR 0.351; 95% CI 0.284–0.434). Additional baseline and safety data by PSA level will be reported. Conclusions: The combination of DARO + ADT and docetaxel significantly prolonged the time to PSA progression and more pts receiving DARO vs PBO achieved undetectable PSA levels, reflecting strong PSA response over time. In pts with mHSPC, achievement of undetectable PSA at 24 and 36 weeks was associated with improved OS, with risk of death reduced by 60% and 65%, respectively, vs those who did not achieve undetectable PSA at 24 and 36 weeks. Clinical trial information: NCT02799602.

Focal therapy for prostate cancer with irreversible electroporation: Oncological and functional results of a single institution study.

PurposeFocal irreversible electroporation (IRE) for prostate cancer aims to reduce quality of life complications, however outcomes data remains limited. We aimed to evaluate histological in-field clearance of prostate cancer at ≥12 months post-IRE.Materials and MethodsRetrospective review of prospectively acquired data of consecutive patients treated between August 2018 and August 2021. Significant recurrence was defined as a ≥6 mm core Gleason 3+3, or ≥Gleason 3+4 with ≥4 mm tumour length. A second definition of any focus of International Society of Urological Pathology (ISUP) ≥2 was also analysed.ResultsThe median follow-up of the entire cohort is 23 months (range 3–39 mo). For 64 primary IRE procedures, surveillance biopsy was performed in 40/50 (80.0%) with ≥12 months follow-up. Significant in-field recurrence occurred in 3/40 (7.5%), or 4/40 (10.0%) with any focus of ISUP >2. Significant out-of-field recurrence occurred in 5/40 (12.5%). In salvage IRE, three patients (3/6, 50.0%) have undetectable prostate-specific antigen levels, two have no residual cancer on biopsy and one patient had out-of-field recurrence. For sexually active men, erectile function was maintained in 24/28 (85.7%) of primary IRE. No incontinence developed in primary IRE (0/64).ConclusionsFocal primary IRE for prostate cancer is associated with 90% infield ablation of any ISUP grade >2 cancer with a low risk of urinary incontinence or impotence. Surveillance prostate biopsies are required to exclude progression despite a normal post-IRE multiparametric magnetic resonance imaging (mpMRI). Salvage IRE is a promising option for localised recurrence after prostate radiotherapy with low morbidity.

The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy.

Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.

Randomized Phase 2 Trial of Abiraterone Acetate Plus Prednisone, Degarelix, or the Combination in Men with Biochemically Recurrent Prostate Cancer After Radical Prostatectomy

BackgroundPhase 2 trial endpoints that can be utilized in high-risk biochemical recurrence (BCR) after prostatectomy as a way of more rapidly identifying treatments for phase 3 trials are urgently needed. The efficacy of abiraterone acetate plus prednisone (AAP) in BCR is unknown. ObjectiveTo compare the rates of complete biochemical responses after testosterone recovery after 8 mo of AAP and degarelix, a gonadotropin-releasing hormone antagonist, alone or in combination. Design, setting, and participantsPatients with BCR (prostate-specific antigen [PSA] ≥1.0 ng/ml, PSA doubling time ≤9 mo, no metastases on standard imaging, and testosterone ≥150 ng/dl) after prostatectomy (with or without prior radiotherapy) were included in this study. InterventionPatients were randomized to AAP (arm 1), AAP with degarelix (arm 2), or degarelix (arm 3) for 8 mo, and monitored for 18 mo. Outcome measurements and statistical analysisThe primary endpoint was undetectable PSA with testosterone >150 ng/dl at 18 mo. Secondary endpoints were undetectable PSA at 8 mo and time to testosterone recovery. Results and limitationsFor the 122 patients enrolled, no difference was found between treatments for the primary endpoint (arm 1: 5.1% [95% confidence interval {CI}: 1–17%], arm 2: 17.1% [95% CI: 7–32%], arm 3: 11.9% [95% CI: 4–26%]; arm 1 vs 2, p = 0.93; arm 2 vs 3, p = 0.36). AAP therapy showed the shortest median time to testosterone recovery (36.0 wk [95% CI: 35.9–36.1]) relative to degarelix (52.9 wk [95% CI: 49.0–56.0], p < 0.001). Rates of undetectable PSA at 8 mo differed between AAP with degarelix and degarelix alone (p = 0.04), but not between AAP alone and degarelix alone (p = 0.12). Limitations of this study include a lack of long-term follow-up. ConclusionsRates of undetectable PSA levels with testosterone recovery were similar between arms, suggesting that increased androgen suppression with AAP and androgen deprivation therapy (ADT) is unlikely to eradicate recurrent disease compared with ADT alone. Patient summaryWe evaluated the use of abiraterone acetate plus prednisone (AAP) and androgen deprivation therapy (ADT), AAP alone, or ADT alone in men with biochemically recurrent, nonmetastatic prostate cancer. While more men who received the combination had an undetectable prostate-specific antigen (PSA) level at 8 mo on treatment, once men came off treatment and testosterone level rose, there was no difference in the rates of undetectable PSA levels. This suggests that the combination is not able to eradicate disease any better than ADT alone.

Whole blood GRHL2 expression as a prognostic biomarker in metastatic hormone-sensitive and castration-resistant prostate cancer.

BackgroundAs potent systemic therapies transition earlier in the prostate cancer disease course, molecular biomarkers are needed to guide optimal treatment selection for metastatic hormone-sensitive prostate cancer (mHSPC). The value of whole blood RNA to detect candidate biomarkers in mHSPC remains largely undefined.MethodsIn this cohort study, we used a previously optimised whole blood reverse transcription polymerase chain reaction assay to assess the prognostic utility [measured by seven-month undetectable prostate-specific antigen (PSA) and time to castration-resistance (TTCR)] of eight prostate cancer-associated gene transcripts in 43 mHSPC patients. Transcripts with statistically significant associations (P<0.05) were further investigated in a metastatic castration-resistant prostate cancer (mCRPC) cohort (n=119) receiving contemporary systemic therapy, exploring associations with PSA >50% response (PSA50), progression-free survival (PFS) and overall survival (OS). Clinical outcomes were prospectively collected in a protected digital database. Kaplan-Meier estimates and multivariable Cox proportional-hazards models assessed associations between gene transcripts and clinical outcomes (mHSPC covariates: disease volume, docetaxel use and haemoglobin level; mCRPC covariates: prior exposure to chemotherapy or ARPIs, haemoglobin, performance status and presence of visceral disease). Follow-up was performed monthly during ARPI treatment, three-weekly during taxane chemotherapy, and three-monthly during androgen deprivation therapy (ADT) monotherapy. Serial PSA measurements were performed before each follow-up visit and repeat imaging was at the discretion of the investigator.ResultsDetection of circulating Grainyhead-like 2 (GRHL2) transcript was associated with poor outcomes in mHSPC and mCRPC patients. Detectable GRHL2 expression in mHSPC was associated with a lower rate of seven-month undetectable PSA levels (25% vs. 65%, P=0.059), and independently associated with shorter TTCR (HR 7.3, 95% CI: 1.5–36, P=0.01). In the mCRPC cohort, GRHL2 expression predicted significantly lower PSA50 response rates (46% vs. 69%, P=0.01), and was independently associated with shorter PFS (HR 3.1, 95% CI: 1.8–5.2, P<0.001) and OS (HR 2.9, 95% CI: 1.6–5.1, P<0.001). Associations were most apparent in patients receiving ARPIs.ConclusionsDetectable circulating GRHL2 was a negative prognostic biomarker in our mHSPC and mCRPC cohorts. These data support further investigation of GRHL2 as a candidate prognostic biomarker in metastatic prostate cancer, in addition to expanding efforts to better understand a putative role in therapeutic resistance to AR targeted therapies.

Clinicopathologic Study of Gleason Pattern 5 Prostatic Adenocarcinoma With "Single-cell" Growth Reveals 2 Distinct Types, One With "Plasmacytoid" Features.

Each Gleason score category of prostatic adenocarcinoma (or Grade Group) may encompass a diverse group of architectural patterns such as well-formed glands, poorly formed glands, cribriform structures, single cells, and/or solid sheets. We have noted heterogeneity within the single-cell subtype of Gleason pattern 5 prostatic adenocarcinoma that has not been fully addressed. Therefore, we retrospectively reviewed a series of radical prostatectomies with high-grade prostatic adenocarcinoma (Grade Group 4 or 5), identifying tumors with a component of single-cell infiltration. Additional cases identified prospectively were also included. TNM status, association with other histologic patterns, and clinical follow-up status were determined. Immunohistochemistry for NKX3.1, E-cadherin, p120 catenin, and prostate-specific antigen (PSA) were performed in each case. Eighteen cases with a component of well-developed Gleason pattern 5 characterized by single infiltrative cells that comprised ≥5% of the tumor were identified (15/202 retrospective radical prostatectomies with the high-grade disease [7.5%]). The single-cell pattern ranged from 5% to 50% of the tumor volume, with 5 cases containing ≥40%, and variable secondary architecture included diffuse infiltrating single cells with targetoid growth pattern around benign glands, solid expansive nests of noncohesive cells, and corded/single file growth pattern. Further morphologic analysis demonstrated 2 distinct histologic subtypes: (1) (subtype 1; n=9) monomorphic "plasmacytoid" tumor cells with eccentrically placed nuclei and variable intracytoplasmic vacuoles with bland cytology and discohesion and (2) (subtype 2; n=9) more cohesive tumor cells with greater cytologic atypia characterized by prominent nucleoli, greater variability in nuclear size/shape, occasional mitotic figures, and more irregular infiltration. By immunohistochemistry, NKX3.1 nuclear expression and PSA cytoplasmic expression was retained in all cases. Concomitant membranous E-cadherin loss and strong cytoplasmic p120 catenin expression were present in 5 of the 18 (28%) cases, all in subtype 1 (5/9, 56%). Overall, 56% (10/18) of patients had advanced-stage disease (≥pT3b), and 70% (7/10) of these patients had associated lymphovascular invasion. All patients had concomitant cribriform patterns of carcinoma. The outcome was available for 14 patients: 4 died of unknown cause; 6 had biochemical recurrence with distant bone metastasis in 5 of the 6; and 4 patients with <3 years of follow-up currently have undetectable serum PSA levels (2 patients received salvage radiotherapy with androgen deprivation and 2 remain on routine follow-up). In summary, the single-cell pattern of Gleason pattern 5 prostatic adenocarcinoma is uniformly associated with other high-risk histologic patterns (eg, cribriform growth), and high-stage disease with distant metastasis is not uncommon. Our data suggest that the "single-cell" Gleason pattern 5 prostatic adenocarcinoma contains 2 distinct subtypes. Somatic CDH1 alterations may play a role in the development of the "plasmacytoid" pattern characterized by monomorphic cytology with concomitant E-cadherin loss and aberrant p120 catenin expression.

Is There Any Role for 18F-Fluciclovine PET/CT in the Presence of Undetectable PSA in Prostate Cancer Patients After Definitive Treatment?

The aim of this study was to investigate the role of F-fluciclovine PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment in the presence of undetectable prostate-specific antigen (PSA). This retrospective study was conducted in PC patients who had undetectable PSA level and underwent fluciclovine PET/CT within a 2-week interval of PSA examination and without interval treatment or other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on fluciclovine PET/CT were collected. Comparisons between groups of positive and negative fluciclovine PET/CT were done by using descriptive statistics. A total of 34 fluciclovine PET/CTs from 34 patients met the inclusion criteria. There were 4 positive (11.8%) and 30 negative fluciclovine PET/CTs (88.2%). All of the patients with positive results had an initial Gleason score of 7 or higher and locally advanced tumor (T3-T4). More common features at the time of diagnosis among positive study patients as compared with negative ones were atypical histologic variants (25% vs 0%) and very high-risk PC (50% vs 30%). Most of the patients with positive study received second-line hormonal therapy (HT) (50%), whereas patients with negative results received first-line HT (53.3%). Chemotherapy naivety was less common among positive patients (75% vs 96.7%). Sites of involvement on positive fluciclovine PET/CTs were pelvic lymph nodes (2/4, 50%), lung and mediastinal lymph node (1/4, 25%), and prostatectomy bed (1/4, 25%). In the presence of undetectable PSA in PC patients after definitive treatment, fluciclovine PET/CT would benefit most to patients with Gleason score of 7 or higher, high disease burden (T3-T4), and atypical histologic variants at the time of diagnosis, and the ones who have history of second-line HT and/or chemotherapy.

Outcomes of salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

Salvage radiotherapy (SRT) provides effective biochemical control for patients with prostate cancer who have prostate specific antigen (PSA) failure after radical prostatectomy. However, the effect of SRT on long-term clinical outcomes remains unknown. Therefore, we report the natural history of patients treated with SRT. We identified 84 Chinese patients with prostate cancer treated with SRT to the prostatic fossa alone during 2006-2017 at Tuen Mun Hospital, Hong Kong. Survival was calculated using Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters with outcomes. Median SRT dose given was 70 Gy (range, 64-76 Gy). Median pre-SRT PSA level was 0.4 ng/mL (0.2-7.4 ng/mL). After SRT, 47 (56%) patients had undetectable (<0.1 ng/mL) PSA levels. After median follow-up of 48 months (2 months to 10 years), 25 (30%) patients had further biochemical progression. Subsequently, 12 patients received androgen deprivation therapy and nine (11%) developed distant metastasis. The 5-year biochemical progression-free survival, androgen deprivation therapy-free survival and metastasis-free survival were 62.7%, 83.5% and 86.7%, respectively. Early PSA failure after radical prostatectomy (hazard ratio 7.4), negative surgical margin (hazard ratio 2.7), positive extracapsular extension (hazard ratio 4.6), and detectable PSA levels after SRT (hazard ratio 17.3) were associated with lower biochemical progression-free survival after SRT. High-dose SRT with intensity-modulated radiotherapy/volumetric modulated arc radiotherapy is an effective local treatment that can prevent distant metastasis and avoid the need for androgen deprivation therapy in Chinese patients who have PSA failure after radical prostatectomy.

Time to Disease Recurrence Is a Predictor of Metastasis and Mortality in Patients with High-risk Prostate Cancer Who Achieved Undetectable Prostate-specific Antigen Following Robot-assisted Radical Prostatectomy.

BackgroundRobot-assisted radical prostatectomy (RARP) is a feasible treatment option for high-risk prostate cancer (PCa). While patients may achieve undetectable prostate-specific antigen (PSA) levels after RARP, the risk of disease progression is relatively high. We investigated metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS) outcomes and prognosticators in such patients.MethodsIn a single-center cohort of 342 patients with high-risk PCa (clinical stage ≥ T3, biopsy Gleason score ≥ 8, and/or PSA levels ≥ 20 ng/mL) treated with RARP and pelvic lymph node dissection between August 2005 and June 2011, we identified 251 (73.4%) patients (median age, 66.5 years; interquartile range [IQR], 63.0–71.0 years) who achieved undetectable PSA levels (< 0.01 ng/mL) postoperatively. Survival outcomes were evaluated for the entire study sample and in groups stratified according to the time to biochemical recurrence dichotomized at 60 months.ResultsDuring the median follow-up of 75.9 months (IQR, 59.4–85.8 months), metastasis occurred in 38 (15.1%) patients, most often to the bones, followed by the lymph nodes, lungs, and liver. The 5-year metastasis-free, cancer-specific, and OS rates were 87.1%, 94.8%, and 94.3%, respectively. Multivariate Cox-regression analysis revealed time to recurrence as an independent predictor of metastasis (P < 0.001). Time to metastasis was an independent predictor of OS (P = 0.003). Metastasis-free and CSS rates were significantly lower among patients with recurrence within 60 months of RARP (log-rank P < 0.001).ConclusionRARP confers acceptable oncological outcomes for high-risk PCa. Close monitoring beyond 5 years is warranted for early detection of disease progression and for timely adjuvant therapy.

Outcomes of salvage radical prostatectomy following more than one failed local therapy.

PurposeTo describe the salvage radical prostatectomy (sRP) experience in patients presenting with recurrent, clinically localized prostate cancer after multiple failed local treatments.Materials and MethodsAmong the 251 sRP performed during 2000–2016, 11 patients had failed multiple local therapies. We describe baseline clinical characteristics at primary cancer diagnosis and prior to sRP, surgical information, complications and oncological outcomes.ResultsThe mean±standard deviation age at sRP was 65±5 years and the median (interquartile range) serum prostate-specific antigen (PSA) level was 2 (1.3) ng/mL. The most common first and subsequent treatments were radiotherapy and cryotherapy, respectively, with median time of 24 months from the last local treatment. The median operative time was 180 minutes and median estimated blood loss was 750 mL. Five (45.5%) patients underwent additional procedures during sRP for pre-operative morbidity from prior treatments (rectourethral fistula, urethral stricture, incontinence). Post-operative complications requiring invasive intervention occurred in 7 (63.6%) patients. Over a median follow-up of 29 (12–96) months, 10 of the 11 men (90.9%) achieved an undetectable PSA in after sRP. Three of these men with an initially undetectable PSA level experienced biochemical recurrence; the remaining 7 are without evidence of disease. Overall, no local recurrence or systemic metastasis was identified at last follow-up.ConclusionssRP is technically feasible and offers durable cancer control in patients with recurrent prostate cancer despite having undergone multiple prior attempts at cure. These patients experience higher rates of post-operative complications and such patients must be appropriately counseled regarding the potential risks and benefits.

Secondary Urethral Malignancies Following Prostate Brachytherapy

To understand urethral secondary malignancies among patients treated with brachytherapy (BRT) for primary prostate cancer. Institutional retrospective review identified 13 patients evaluated from 2003 to 2014 with urethral cancer and history of BRT monotherapy for prostate cancer. All patients were biochemically free of their primary disease and radiation-associated secondary malignancies (RASMs) were confirmed pathologically to be histologically distinct from primary tumor. BRT characteristics, patient age, presentation, staging workup, and clinical course were evaluated. The mean time from BRT to presenting symptoms of hematuria, urinary retention, and/or renal failure was 71 months. Symptom onset to RASM diagnosis interval was 24 months. Mean time from BRT to RASM diagnosis was 95 months. Eighty-five percent of patients had an undetectable prostate-specific antigen level (<0.2 ng/mL) at last follow-up. Types of RASM included sarcomatoid carcinoma (6), small cell carcinoma (2), urothelial carcinoma with squamous differentiation (2), squamous cell carcinoma (1), rhabdomyosarcoma (1), and urothelial carcinoma (1). A majority of patients were diagnosed with advanced disease with either distant metastases (54%) or local progression (23%). Ten patients died during this study period with median time to death after RASM diagnosis of 6 months. RASMs localized to the posterior urethra displayed advanced disease and high mortality rates. Refractory lower urinary tract symptoms, hematuria, and history of prostate BRT should raise suspicion for urethral RASMs. Further studies are warranted to determine patient and disease characteristics that correlate with disease-specific mortality of secondary urethral malignancies.

Determining When to Stop Prostate Specific Antigen Monitoring after Radical Prostatectomy: the Role of Ultrasensitive Prostate Specific Antigen

We analyzed long-term followup data after radical prostatectomy to determine how long we should follow patients in whom the serum prostate specific antigen level measured by an ultrasensitive assay was consistently low. We retrospectively reviewed clinicopathological data for 582 consecutive patients who underwent open or laparoscopic radical prostatectomy between 1995 and 2004, excluding 4 patients who received adjuvant therapy. We stratified the patients according to prostate specific antigen at 3 and 5 years after surgery, and examined subsequent biochemical recurrence (elevation of prostate specific antigen to greater than 0.2 ng/ml) during followup. Mean followup was 9.7 years. At 3 years after surgery prostate specific antigen levels were measured by an ultrasensitive assay in 323 patients who had not experienced biochemical recurrence. In 187 patients with undetectable prostate specific antigen levels (less than 0.01 ng/ml) the 10 and 15-year biochemical recurrence-free survival rates were 99% and 96%, respectively. At 5 years after surgery prostate specific antigen was measured in 315 patients by the ultrasensitive assay. In 162 patients with undetectable prostate specific antigen levels the 10 and 15-year biochemical recurrence-free survival rates were both 100%. In this group the prostate specific antigen level at last followup was less than 0.01 ng/ml in 132 patients, 0.01 to 0.03 ng/ml in 27 patients, and 0.06 ng/ml, 0.07 ng/ml and 0.11ng/ml in 1 patient each. This long-term review indicates that if patients have continuously undetectable prostate specific antigen levels by an ultrasensitive assay for 5years, prostate specific antigen monitoring can be stopped with an extremely low risk of subsequent biochemical recurrence.

Salvage prostate cryoablation for recurrent localized prostate cancer after radiotherapy

Salvage prostate cryoablation (SCA) for recurrent localized prostate cancer after radiotherapy has been studied in Western countries for more than a decade. We present our experience of SCA in a Taiwanese medical center. We performed four cases of SCA for recurrent localized prostate cancer after radiotherapy. The data recorded included age, cancer stage, prostate-specific antigen (PSA) level, Gleason score, prostate volume and patient outcome. The median follow-up period was 17 months. All cases were biopsy-proven to have residual cancer before cryoablation. After SCA, 25% of the patients reached undetectable PSA levels, 50% showed response but did not reach undetectable levels, and 25% showed no decrease in PSA. The median recurrence-free duration after SCA was 18 months in the patients who experienced a decrease in PSA. ADT was initiated after SCA for the patient who did not show any response, and bone metastasis was later diagnosed in that patient. Most patients experienced obstructive voiding problems after SCA, which improved over time. SCA is a safe salvage option for prostate cancer patients with local recurrence after RT. The preliminary results are encouraging. More extensive imagery to exclude extra-glandular disease is warranted before SCA. A longer follow-up period and larger sample size are necessary to delineate the benefits more conclusively.

MP18-03 PREDICTORS OF LOCAL DISEASE CONTROL AFTER SALVAGE WHOLE GLAND PROSTATE CRYOABLATION

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy1 Apr 2016MP18-03 PREDICTORS OF LOCAL DISEASE CONTROL AFTER SALVAGE WHOLE GLAND PROSTATE CRYOABLATION Yaw Nyame, Ahmed Elshafei, Hans Aurora, Robert W. Given, Thomas J. Polascik, Ashley E. Ross, Vladimir B. Mouraviev, and J. Stephen Jones Yaw NyameYaw Nyame More articles by this author , Ahmed ElshafeiAhmed Elshafei More articles by this author , Hans AuroraHans Aurora More articles by this author , Robert W. GivenRobert W. Given More articles by this author , Thomas J. PolascikThomas J. Polascik More articles by this author , Ashley E. RossAshley E. Ross More articles by this author , Vladimir B. MouravievVladimir B. Mouraviev More articles by this author , and J. Stephen JonesJ. Stephen Jones More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2704AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The objective of this study was to assess factors that affect prostate biopsy results following salvage whole gland cryoablation METHODS A retrospective analysis of 174 patients who underwent transrectal ultrasound-guided biopsy following salvage whole gland cryoablation of the prostate was performed using the Cryo OnLine Database (COLD). Covariates analyzed included age, ethnicity, initial prostate specific antigen (PSA), clinical stage, Gleason score, D Amico risk stratification, neoadjuvant therapy, PSA nadir, time to nadir, and achievement of undetectable PSA level (<0.2ng/ml). Univariate was performed using Wilcoxon rank-sum test for continuous variables and χ2 test for categorical variables. A multivariate logistic regression analysis was also performed. RESULTS 52/174 (29.8%) patients who underwent prostate biopsy had a positive result following salvage cryoablation with a median time of 11 months to biopsy. On univariate analysis, patients with positive biopsy were more likely to be in the D Amico high-risk category (69.2% vs. 45.9%), more likely to have a higher median PSA nadir (0.7 vs. 0.1, P=0.0001), and less likely to have an undetectable PSA prior to PSA (25.4% vs.57.02%, P= 0.0002). On multivariate analysis, PSA nadir (OR 1.08, P=0.0132) was the only independent factor of post-operative biopsy outcome (Table 1). CONCLUSIONS PSA nadir level following salvage whole gland cryoablation was the only factor that was independently associated with prostate biopsy outcomes on multivariate analysis. This may guide the need for prostate biopsy when local failure following salvage whole gland cryoablation is suspected © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e193 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yaw Nyame More articles by this author Ahmed Elshafei More articles by this author Hans Aurora More articles by this author Robert W. Given More articles by this author Thomas J. Polascik More articles by this author Ashley E. Ross More articles by this author Vladimir B. Mouraviev More articles by this author J. Stephen Jones More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A Phase II Study of AT-101 to Overcome Bcl-2–Mediated Resistance to Androgen Deprivation Therapy in Patients With Newly Diagnosed Castration-Sensitive Metastatic Prostate Cancer

BackgroundWe conducted a phase II study in men with castration-sensitive metastatic prostate cancer to test the hypothesis that AT-101, a small molecule Bcl-2 inhibitor, has clinical activity in patients initiating androgen deprivation therapy (ADT) for metastatic prostate cancer. Materials and MethodsPatients with metastatic prostate cancer scheduled to start, or who had recently (within 6 weeks) initiated, ADT were enrolled. ADT with a luteinizing hormone-releasing hormone agonist and bicalutamide was started 6 weeks before initiation of oral AT-101, 20 mg/day for 21 days of a 28-day cycle. The primary endpoint of the study was the percentage of patients with an undetectable prostate-specific antigen (PSA) level (≤ 0.2 ng/mL) after 7.5 months (1.5 months of ADT alone plus 6 months of combined ADT and AT-101). To assess for an association between chromodomain helicase DNA binding protein 1 (CHD1) and drug sensitivity, fluorescence in situ hybridization with confocal microscopy was assessed in a subgroup of patients. ResultsA total of 55 patients were enrolled, with median age of 61 years and a median PSA level of 27.6 ng/dL. Of the 55 patients, 72% had a Gleason score ≥ 8. Three patients had visceral metastases, and the remaining patients had bone or nodal metastasis. An undetectable PSA level was achieved in 31% of the patients. Of the 31 patients, 12 experienced serious adverse events, 7 of which were considered related to study therapy. Most of the related adverse events were gastrointestinal and nervous system disorders. CHD1 assessment was feasible, with a nonsignificant association with therapeutic sensitivity in a small number of patients. ConclusionThe combination of ADT and AT-101 did not meet the prespecified level of activity for further development of this combination.

Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence of a rare phenomenon

Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma.