Christopher Michael Pieczonka

A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer.

BACKGROUNDnThe 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy.nnnOBJECTIVEnTo perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA.nnnDESIGN, SETTING, AND PARTICIPANTSnProspective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014.nnnINTERVENTIONnThe 4Kscore.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnThe primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis.nnnRESULTS AND LIMITATIONSnGleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review.nnnCONCLUSIONnThe 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer.nnnPATIENT SUMMARYnThe 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy.

Comparison of Fracture Risk Assessment Tool Score to Bone Mineral Density for Estimating Fracture Risk in Patients With Advanced Prostate Cancer on Androgen Deprivation Therapy

OBJECTIVEnTo estimate the risk of fracture (Fracture Risk Assessment Tool [FRAX] algorithm) because of the development of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy (ADT) for patients who would otherwise not have been identified for treatment by the T score.nnnMETHODSnThis study includes men undergoing ADT for prostate cancer at our urology group. Clinical data were collected via chart review. Subjects were evaluated for fracture risk using country specific (for the United States of America) World Health Organizations FRAX. The FRAX calculations were then compared to fracture risk as determined by T score, for a subset of our cohort that received dual-energy X-ray absorptiometry.nnnRESULTSnOur cohort consisted of 613 patients on ADT, 94 of which had a dual-energy X-ray absorptiometry scan. The FRAX algorithm identified 61.6% patients requiring therapy without bone mass density (BMD), 46.8% with BMD, and 19.14% with T score alone. In addition, positive correlation was found between FRAX with and without BMD as well as T score and FRAX with BMD and without BMD.nnnCONCLUSIONnOur data indicate that many patients who were not found at significant risk for fracture with T score were in fact found to be at risk with the FRAX calculation. The largest proportion of patients was found to be at risk through the FRAX calculation without BMD, followed by FRAX with BMD, followed by T score alone. The utility of FRAX is beneficial in identifying patients that may benefit from effective bone-tropic treatment modalities.

Hydrogel Spacer Application Technique, Patient Tolerance and Impact on Prostate Intensity Modulated Radiation Therapy: Results from a Prospective, Multicenter, Pivotal Randomized Controlled Trial

Introduction We evaluate the safety, tolerability and impact on therapy of an absorbable hydrogel perirectal spacer (SpaceOAR® system) designed to reduce the rectal radiation dose during prostate cancer radiotherapy. Methods A multicenter, pivotal, randomized controlled trial was conducted in 222 men with stage T1 or T2 prostate cancer treated to 79.2 Gy with image guided intensity modulated radiation therapy in 44 fractions. Patients were randomized 2:1 to receive fiducial markers and perirectal spacer injection (spacer group) or fiducial markers alone (control group). Spacer placement, tolerability, perirectal space creation, impact on rectal dose and impact on quality of life were assessed. Results Most spacer procedures were conducted with the patient under general or local anesthesia. Procedures were rated easy or very easy in 98.7% of cases with a 99.3% success rate. Mild transient rectal events were noted in 10% of patients in the spacer group (eg pain, discomfort). Mean perirectal space was 12.6 mm after implant and 10.9 mm at 12.4 weeks with absorption at 12 months. A 25% or greater reduction in rectal V70 dose was produced in 97.3% of patients in the spacer group. The spacer group experienced a significant reduction in late rectal toxicity severity (p=0.044) as well as lower rates of decrease in bowel quality of life at 6, 12 and 15 months compared to the control group. There were no unanticipated adverse spacer effects or spacer related adverse events. Conclusions Hydrogel spacer application was straightforward and repeatable, resulting in consistent perirectal space creation and rectal dose reduction. Spacer application has the potential to improve prostate radiotherapy outcomes and enable advanced radiotherapy protocols.

Immune response from STRIDE, a randomized, Phase II, open-label study of sipuleucel-T (sip-T) with concurrent vs sequential enzalutamide (enz) administration in metastatic castration-resistant prostate cancer (mCRPC)

Meeting abstractsnnP12-2 (STRIDE; [NCT01981122][1]) is an ongoing, randomized, Phase II, open-label study evaluating concurrent vs sequential administration of the androgen receptor inhibitor, enz, with the autologous cellular immunotherapy, sip-T. The primary aim of this study is to determine if

Real-world experience with sipuleucel-T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel (D): Data from PROCEED.

30^ Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic mCRPC. The phase III IMPACT trial showed a significant improvement in overall survival with sipuleucel-T treatment (tmt). In IMPACT, D use was prohibited within 3 months prior to registration due to the potential immunosuppressive impact of chemotherapy. PROCEED is an ongoing, multicenter, phase 4 registry enrolling pts receiving sipuleucel-T in the real-world setting. Enrollment has no restrictions on D use; thus, data from PROCEED may help determine whether prior D affects sipuleucel-T manufacture. Here we present preliminary results on baseline demographics and product parameters in PROCEED subjects with and without prior D exposure.nnnMETHODSnPts who were treated with sipuleucel-T within the prior 6-months at clinical sites were asked to provide informed consent to participate in PROCEED.nnnRESULTSnBy September 2012, 560 pts completed sipuleucel-T tmt; 15% previously received D (median 291 days prior to 1st sipuleucel-T infusion). Patients with prior D had higher PSA levels, and those with recent D use tended to have a lower performance status and higher Gleason scores, but product parameters were generally comparable between the groups (see table).nnnCONCLUSIONSnPts enrolled in PROCEED with and without prior D exposure had different baseline demographics and disease characteristics. However, sipuleucel-T product parameters were comparable regardless of prior D exposure.nnnCLINICAL TRIAL INFORMATIONnNCT01306890. [Table: see text].

MP92-10 A RECTAL SWAB GUIDED PROPHYLAXIS PROGRAM ON THE INCIDENCE OF INFECTIOUS COMPLICATIONS FOLLOWING TRANS-RECTAL ULTRASOUND GUIDED PROSTATE BIOPSY AND FIDUCIAL MARKER PLACEMENT

unlike Western nations where high percentages live in urban areas, developing countries have a higher percent living in rural areas or small towns. It is unknown if the benefits of regionalization outweigh the barriers this creates for access. We tested the link between distance from screening site to biopsy (bx) referral center and risk of noncompliance with showing up to have a bx in a population-based PC screening cohort in Brazil. METHODS: We reviewed records from 1,561 men recommended to undergo a bx after an initial PC screen by a medical mobile unit at their local clinic between 2004 and 2007. Bxs were performed at a regional referral center, Barretos Cancer Hospital (BCH). Clinical data between men who complied with the bx vs. not were compared with rank-sum & chi-square. Multivariable logistic regression analysis of distance from screening site to BCH (km) and risk of non-compliance was performed adjusting for age and year of screening. RESULTS: Median distance was 257km (IQR 135-718). Noncompliant men were older (68 vs 66 yrs), had a higher PSA (4.9 vs 4.2), were less likely to have an abnormal DRE (20% vs 33%) and lived further from BCH (921 vs 225 km) (all p<0.001). On crude and multivariable analyses, further distance was significantly linked with bx noncompliance (OR/100km 0.83, p<0.001, see figure). Among men who lived within 150km of BCH, distance was unrelated to compliance (OR/ 100km 1.09, p1⁄40.87). CONCLUSIONS: In Brazil, where distances from PC screening to bx clinic can be hundreds of kms, greater distance to referral center was related to reduced compliance to bx. However, among men who lived within 150km, distance was unrelated to compliance. While regionalization of care may in theory improve quality, it comes at the cost of reduced compliance and thus reduced access and represents a significant barrier to optimal care if distances are large. In regards to PC screening and bx, our data suggest distances up to 150km do not create barriers for care. Alternative thresholds, however, may apply for other services and in other cultures.

774PSTRIDE, A RANDOMIZED, PHASE 2, OPEN-LABEL STUDY OF SIPULEUCEL-T WITH CONCURRENT VS SEQUENTIAL ENZALUTAMIDE IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC)

ABSTRACT Aim: Multiple treatment options exist for patients (pts) with mCRPC, particularly in the setting of early metastasis. Sipuleucel-T, an autologous cellular immunotherapy, and enzalutamide, an androgen receptor inhibitor, are approved in the US and EU for treatment of mCRPC, but data are limited regarding use of these agents in combination. P12-2 (STRIDE; NCT01981122) is an ongoing, randomized, open-label, phase 2 study designed to evaluate concurrent vs sequential administration of sipuleucel-T and enzalutamide. Methods: Pts with asymptomatic or minimally symptomatic mCRPC are randomized 1:1 to receive sipuleucel-T with enzalutamide (160u2003mg QD for 52 wk) starting 2 wk before (concurrent arm [A]) or 10 wk after (sequential arm [B]) initiation of sipuleucel-T (3 infusions at 2-wk intervals). The primary endpoint is peripheral T cell immune response to PA2024, the immunizing antigen for sipuleucel-T. A secondary endpoint is time to recurrence of elevated serum PSA level. Results: As of April 7, 2014, 30 enrolled pts had completed sipuleucel-T infusions. At baseline, demographic and disease characteristics in arm A (n = 12) and arm B (n = 18) were generally comparable. Sipuleucel-T product parameters (antigen presenting cell [APC] activation, APC count, and total nucleated cell [TNC] count) did not differ significantly between the arms. A prime-boost effect on APCs was evident in both arms, as indicated by greater APC activation at infusions 2 and 3 than at infusion 1. The nature and incidences of adverse events (AEs) appeared to be similar between the arms and consistent with those previously reported with sipuleucel-T and enzalutamide. Overall, AEs occurred in 6 (50%) pts in arm A and 11 (61%) pts in arm B. Within 1 day of sipuleucel-T infusion, AEs occurred in 3 (25%) pts in arm A and 4 (22%) pts in arm B. No treatment-related grade ≥3 AEs were reported. Conclusions: Preliminary data suggest that sipuleucel-T potency, prime-boost, and safety are similar with and without concurrent enzalutamide. Data describing sipuleucel-T-induced peripheral immune responses with concurrent vs sequential enzalutamide will be presented at the meeting. Disclosure: D.P. Petrylak: Consultant or Advisory Role - Dendreon Corporation, Astellas - Self, compensated Corporate-sponsored Research - Dendreon Corporation, Astellas - Self, compensated; D.I. Quinn: Consultant, Honoraria: Dendreon, Medivation, Astellas, Pfizer, Bayer, Aveo, Algeta, Novartis, Amgen, Prometheus, Fresenius, Genentech, Jannsen-Self, compensated Sponsored research: Millenium, Sanofi-Aventis–Self Expert testimony: Medivation, Teva-Self; R. Dreicer: Consultant or Advisory Role: Medivation, Janssen, Dendreon, Roche, Millenium, Sanofi Aventis-Self, compensated Corporate-sponsored research: BIND, Progenics, Roche-Self; E.S. Antonarakis: Consultant or Advisory Role: Dendreon Corporation-Self, compensated Corporate-sponsored Research: Dendreon Corporation-Self; N.D. Shore: Consultant or Advisory Role: Algeta, Astellas, Bayer, Dendreon,Pfizer, Millenium, Janssen, Medivation, Sanofi-Self, compensated; J. Corman: Corporate-sponsored research: Dendreon Corporation-self R. Concepcion: Consultant or Advisory Role: Dendreon, Algeta, Bayer, MDxHealth, Cardinal Health,Chan Soon-Shiong Institute for Advanced Health-Self, compensated Corporate-sponsored Research: Janssen, Dendreon, Medivation, BNIT-Self; C.M. Pieczonka: Stock Ownership: Algeta-Self Consultant or Advisory Role: Dendreon-Self, compensated Honoraria: Dendreon, Astellas-Self; A.C. Stubbs: Employment: Dendreon Corporation-Self, compensated Stock Ownership: Dendreon Corporation-Self; N. Sheikh: Employment: Dendreon Corporation-Self, compensated Stock Ownership: Dendreon Corporation-Self; T. Devries: Employment: Dendreon Corporation Stock Ownership: Dendreon Corporation; A.S. Sandler: Employment: Dendreon Corporation Stock Ownership: Dendreon Corporation; C.G. Drake: Consultant or Advisory Role: Bristol Myers Squibb, Dendreon, Janssen, Pfizer, Roche-Self, compensated Corporate-sponsored Research: Aduro, Bristol Myers Squibb, Janssen-Self.