Mark C. Scholz

Cell cycle progression score and treatment decisions in prostate cancer: results from an ongoing registry

Abstract Objective: The cell cycle progression (CCP) test (Prolaris) is a novel prognostic assay that provides accurate risk of prostate cancer-specific disease progression and disease specific mortality when combined with standard clinicopathologic parameters. This prospective study evaluated the impact of the CCP report on physician treatment recommendations for prostate cancer. Methods: Physicians ordering the CCP test in clinical practice completed surveys regarding treatment recommendations before and after they received and discussed the test results with patients. Clinicians also rated the influence of the test result on treatment decisions. Treatment selections were confirmed via third-party audit of patient charts following final survey responses. Results: Overall, 65% of cases showed a change between intended treatment pre- and post-CCP test reporting. Pre-CCP testing, 164 of 305 cases received a recommendation for interventional treatment. Post-CCP test, interventional therapy was recommended for 103 of these cases, a reduction of 37.2%. Conversely, 141 of 305 cases were recommended pre-CCP testing for non-interventional treatment; 108 of these remained with non-interventional treatment while 33 shifted to interventional options, a 23.4% increase. There was a 49.5% reduction in surgical interventions and a 29.6% reduction in radiation treatment. A third-party audit identified 80.2% concordance between the post-CCP testing treatment recommendation and actual treatment. Re-assignment to intervention or non-intervention generally correlated with the result of the CCP report. Study limitations included physician selection of patients for testing, no evaluation of patient input in therapeutic choice, and other potential treatment decision factors not queried by the survey. Conclusion: Based on responses of ordering physicians, the CCP report adds meaningful new information to risk assessment for localized prostate cancer patients. Test results led to changes in treatment with reductions and increases in interventional treatment that were directionally aligned with prostate cancer risk specified by the test.

Intermittent Use of Testosterone Inactivating Pharmaceuticals Using Finasteride Prolongs the Time Off Period

PURPOSE Men with prostate cancer treated intermittently with TIP benefit from improved quality of life when TOP with recovered testosterone is prolonged. We examined factors influencing the duration of TOP. MATERIALS AND METHODS We retrospectively reviewed the charts of 101 men treated with intermittent TIP in a 9-year period. Men with positive bone scan, men in whom a PSA nadir of less than 0.1 ng/ml on TIP failed to be achieved and maintained and men in whom testosterone failed to recover to greater than 150 ng/dl during the first 12 months of TOP were excluded. Potential factors predicting prolonged TOP or accelerated time to AIPC were studied with Cox regression analysis. RESULTS Patient characteristics were clinical stage T1c-T2a in 51 and T2b-T3b in 11, PSA relapse in 29, and T3c, D0 or D1 in 10. Median PSA was 7.6 ng/ml, Gleason score was 3 + 4 = 7 and TIP duration was 15.8 months. The 60 group 1 patients received finasteride and the 41 in group 2 received no finasteride. Median TOP in groups 1 and 2 was 31 and 15 months, respectively, using Kaplan-Meier analysis. Cox regression analysis indicated that longer TIP, finasteride and increased age predicted longer TOP. A slow PSA decrease while on TIP, higher baseline PSA and increased Gleason score predicted shorter TOP. Cox regression analysis indicated that only higher clinical stage but not finasteride predicted the earlier onset of AIPC. CONCLUSIONS Finasteride doubles the duration of TOP. AIPC was not increased by finasteride after almost 9 years of observation.

Primary Intermittent Androgen Deprivation As Initial Therapy for Men with Newly Diagnosed Prostate Cancer

BACKGROUND The purpose of this study was to describe the long-term incidence of cancer progression and mortality in men with localized prostate cancer treated with primary androgen deprivation (AD). METHODS A retrospective chart review, from a medical oncology practice specializing in prostate cancer, was conducted of 73 men eligible for surgery or radiation treated with induction AD. Entry criteria consisted of a minimum of 9 months of induction AD, treatment initiation before 1999, clinical stage < T3, and outcome defined as the incidence of delayed local therapy, cancer progression, cancer mortality, and mortality from other causes. RESULTS Median follow-up was 12 years. Fifteen men were at low risk, 38 were at intermediate risk, and 20 were at high risk. Three men (4%) experienced metastatic disease and died of prostate cancer after 3.5, 7.7, and 11 years, respectively. Two men were in the intermediate-risk category and 1 was high risk. Nineteen men (26%) died of non-prostate cancer causes. None had metastatic disease at the time of death. Of the remaining 51 survivors, none has experienced bone metastasis. Twenty-one men (29%) required no further therapy after the first induction course of AD. Twenty-four men (33%) maintained a prostate-specific antigen (PSA) level < 5.0 ng/mL with 2 to 5 cycles of intermittent AD. Twenty-eight men (38%) underwent delayed local therapy after a median of 5.5 years. Median follow-up after local therapy was 6.2 years. Three of these men experienced subsequent rising PSA levels but none has progressed to bone metastasis. Sixteen of 20 men (80%) in the high-risk category but only 12 of 53 men (23%) in the low- and intermediate-risk categories had delayed local therapy. CONCLUSIONS Primary intermittent AD is feasible for men with localized prostate cancer. Men who are younger and men with high-risk disease undergo delayed local therapy more frequently.

Safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: expanded access in North America.

The open‐label, single‐arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration‐resistant prostate cancer (mCRPC) who had previously received docetaxel.

Phase I clinical trial of sipuleucel-T combined with escalating doses of ipilimumab in progressive metastatic castrate-resistant prostate cancer

Background Sipuleucel-T (SIP-T), which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI) achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic. Patients and Methods Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC) were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T. Three patients were evaluated at each level. Cancer-specific immunoglobulins directed at granulocyte-macrophage-colony-stimulating factor/prostatic acid phosphatase (PAP) fusion protein (PA2024) and PAP were measured prior to SIP-T, after SIP-T, 1 week after IPI, every other month for 5 months, then every 3 months for an additional 12 months. Results Adverse events of SIP-T were consistent with previous reports. IPI only caused a transient grade 1 rash in one patient. Median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Eight men had bone metastases and one had lymph node metastasis. Statistically significant increases in serum immunoglobulin G (IgG) and IgG-IgM specific for PA2024 and PAP occurred after SIP-T. An additional statistically significant increase in the aforementioned immunoglobulins – above the levels achieved by SIP-T – occurred after IPI. Median clinical follow-up was 36 months (range: 26–40). Three patients died from progressive disease after 9, 18, and 20 months. Out of the remaining six patients, five of them needed further treatment that included abiraterone acetate, enzalutamide, radium-223 dichloride, and spot radiation. One patient had an undetectable PSA, who did not receive any other treatment except spot radiation. Median PSA at last follow-up for the surviving patients was 3.8 (range: 0.6–7.47). Conclusion In this small trial, the addition of IPI to SIP-T was well tolerated. IPI increased immunoglobulins specific for the PA2024 protein and PAP above the level achieved with SIP-T alone.

Primary androgen deprivation (AD) followed by active surveillance (AS) for newly diagnosed prostate cancer (PC): A retrospective study.

Active surveillance (AS) is only recommended for Low‐Risk prostate cancer (PC) with <34% biopsies positive. Studies describing the long‐term outcome of men treated with androgen deprivation (AD) followed by AS are sparse.

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. METHODS Pts who were treated with sipuleucel-T within the prior 6-months at clinical sites were asked to provide informed consent to participate in PROCEED. RESULTS By 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). CONCLUSIONS Pts 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. CLINICAL TRIAL INFORMATION NCT01306890. [Table: see text].