665: Baseline PSA and PSA Doubling Time Predict the Risk of Objective Progression and Death in Patients with T0-4 N0-2 M0 Prostate Cancer on Watchful Waiting

230 Background: There are conflicting data as to the benefit of treating patients with biochemically recurrent prostate cancer (PCa). Plant derivatives, called “nutraceuticals” such as grape seed extract or milk thistle, have been studied as therapies for PCa based on their purported anti-inflammatory and anti-oxidant properties and low toxicities. Acai is a fruit rich in bioflavinoids shown to induce apoptosis in preclinical studies of PCa, leukemia and esophageal cancer. Anecdotal experience of two patients with falling prostate specific antigen (PSA) values while consuming acai juice prompted us to evaluate its efficacy in a clinical trial. Methods: This was a phase II Simon two-stage open-label single-arm single-institution study of the efficacy of Acai Juice Product in asymptomatic PCa patients with a rising PSA. Eligibility included lack of current hormone therapy, hormone sensitivity, and a PSA doubling time of >4 weeks. Patients consumed 2 oz of Acai Juice Product twice daily for 30 weeks, with a primary endpoint of PSA response. Secondary endpoints included PSA doubling time, PSA velocity, and duration of PSA response. Progression was defined as a rise of 25% from baseline PSA with absolute rise of 2ng/dL. Results: 21 patients were enrolled in the first stage of the trial. Median baseline PSA was 2.74 (range 0.38-36.88). Eighteen patients have completed therapy with 1 PSA response. In the one responder, the patient entered with a doubling time of 4 months and a PSA of 12.57, which was 2.15 at 36 weeks suggesting a prolonged and continued response. PSA either decreased or doubling time prolonged from baseline in 18 patients. PSA velocity was a negative rate of change per month in 4 patients. Conclusions: Acai juice did not produce enough PSA responses in this patient population to proceed beyond the first stage of this trial. However, PSA doubling time did slow in 85.7% of patients, and the one observed PSA response was sustained over at least 36 weeks at the time of data cutoff. Thus, we will analyze potential cellular signals through an M30 Apotosense ELISA assay and Human Cytokine 10-plex panel on patient samples with data available for presentation at the meeting. Clinical trial information: NCT01521949.

Download Full-text

231 oral Localized prostate cancer: watchful waiting vs. definitive therapy based on psa doubling time, the change in histologic grade on rebiopsy, and the extent of clinical progression

Radiotherapy and Oncology ◽

10.1016/s0167-8140(01)80372-8 ◽

2001 ◽

Vol 58 ◽

pp. S66-S67

Keyword(s):

Prostate Cancer ◽

Doubling Time ◽

Watchful Waiting ◽

Histologic Grade ◽

Localized Prostate Cancer ◽

Clinical Progression ◽

Psa Doubling Time ◽

Definitive Therapy

Download Full-text

Prospective evaluation of a “Watchful Waiting” program using initial pathology criteria and PSA-doubling time monitoring for patients with stage T1c prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14651 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14651-14651

Author(s):

Y. Kakehi ◽

T. Kamoto ◽

O. Ogawa ◽

K. Tobisu ◽

Y. Saito ◽

...

Keyword(s):

Prostate Cancer ◽

Doubling Time ◽

Watchful Waiting ◽

Point Estimate ◽

Aggressive Treatment ◽

Eligibility Criteria ◽

Psa Doubling Time ◽

Early Dropout ◽

Positive Core

14651 Background: “Watchful waiting (WW)” is becoming a common treatment option for patients (pts) with screening detected prostate cancer. There is, however, no consensus about which pts are suitable for WW and how pts are monitored. Methods: Eligibility criteria: 1) stage T1c prostate cancer pts, 2) age 50–80, 3) serum PSA: 20 ng/ml or less, 4) 1 or 2 positive cores per 6 to 12 systematic core biopsies, 5) Gleason score of 6 or less, 6) 50% or less maximum % cancer occupation in a positive core. The criteria of 4), 5), 6) were confirmed by a central pathologist before pts registration. Registered patients chose either WW or immediate aggressive treatment. In patients who chose WW, serum PSA was monitored every 2 months for 6 months and PSA-doubling time (PSADT) was calculated centrally. Those who showed PSADT 2y and re-biopsy at 13 months fit the initial pathology criteria again. Primary endpoint was “% PSADT > 2 y”, which was defined as proportion of patients who showed PSADT at 6 months > 2 y out of all patients who chose WW. Point estimate of “% PSADT > 2 y” was expected to be higher than 80%. The planned sample size was 100 pts who chose WW, which gives the width of 95% confidence intervals for % PSADT > 2 y within 10%. Results: 134 pts were enrolled from 01/2002 to 12/2003 and 118 pts chose WW while 13 pts chose aggressive treatment (surgery, radiotherapy, hormonal therapy). The initial 6 months’ PSADT could be assessed in 106 patients (measurement point error in 6, early dropout in 6). Of 106 patients, 22 showed PSADT < 2 y (“rapid riser”) while 84 showed PSADT > 2 y. “% PSADT > 2 y” was 71.2% (84/118, 95% CI: 62.1–79.2%). 84 pts have continued WW with median follow-up of 27 months. Neither metastasis nor cancer-death was observed until 06/2005. As to health-related QOL, any domain of SF-36 was not impaired in patients who continued WW at least for 1 year. Conclusion: Our initial selection criteria for WW may include at least 20% of “rapid riser”, hence need further modification. Additionally, it should be confirmed by further follow-up of 84 pts whether eliminating “rapid riser” from WW by initial 6 months’ PSADT is appropriate. No significant financial relationships to disclose.

Download Full-text

PSA DOUBLING TIME AS PREDICTOR OF OBJECTIVE PROGRESSION AND DEATH IN PATIENTS WITH T0-4 N0-2 M0 PROSTATE CANCER NOT SUITABLE FOR LOCAL DEFINITIVE TREATMENT ON WATCHFUL WAITING (EORTC 30891)

European Urology Supplements ◽

10.1016/s1569-9056(06)60727-6 ◽

2006 ◽

Vol 5 (2) ◽

pp. 203 ◽

Cited By ~ 6

Author(s):

L. Collette ◽

U.E. Studer ◽

P. Whelan ◽

W. Albrecht ◽

J. Casselman ◽

...

Keyword(s):

Prostate Cancer ◽

Doubling Time ◽

Watchful Waiting ◽

Definitive Treatment ◽

Psa Doubling Time

Download Full-text

Variations in PSA doubling time in patients with prostate cancer on “watchful waiting”: Value of short-term PSADT determinations

Urology ◽

10.1016/j.urology.2004.03.020 ◽

2004 ◽

Vol 64 (2) ◽

pp. 323-328 ◽

Cited By ~ 16

Author(s):

Phillip L Ross ◽

Salaheddin Mahmud ◽

Andrew J Stephenson ◽

Luis Souhami ◽

Simon Tanguay ◽

...

Keyword(s):

Prostate Cancer ◽

Doubling Time ◽

Watchful Waiting ◽

Short Term ◽

Psa Doubling Time

Download Full-text

Resolution of the Expert Council on the New Approach to Drug Therapy for Non-Metastatic Castration-Resistant Prostate Cancer

Oncologia i radiologia Kazakhstana ◽

10.52532/2521-6414-2021-1-59-8-11 ◽

2021 ◽

Vol 59 (1) ◽

pp. 8-11

Author(s):

Dilyara Kaidarova ◽

Oxana Shatkovskaya ◽

Zaure Dushimova ◽

Bakytzhan Ongarbayev

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Treatment Efficacy ◽

Doubling Time ◽

Distant Metastases ◽

Diagnostic Methods ◽

Efficacy And Safety ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Psa Doubling Time

Relevance: Prostate cancer (PC) is one of the most common malignant neoplasms in the male population. The widespread introduction of modern diagnostic methods and the determination of prostate-specific antigen (PSA) levels have increased the number of detected cases of localized and locally advanced PC forms. However, in some patients treated with radical methods and long-term androgen deprivation therapy (ADT), the disease continues to progress in the form of an increase in PSA levels with castration testosterone values and with no distant metastases. Such a course of the disease is referred to as non-metastatic castration-resistant prostate cancer (nmCRPC). Purpose: The article reports the results of a meeting of the Expert Council arranged by the Kazakh Research Institute of Oncology and Radiology on December 25, 2020, on non-metastatic castration-resistant prostate cancer diagnostics and treatment. Results: Large clinical studies highlight the critical importance of controlling the PSA doubling time as the main prognostic factor for an unfavorable outcome to increase patient survival and prevent the development of distant metastases. Based on the results of large randomized studies, experts recommended using new-generation androgen receptor antagonists in combination with ongoing ADT to improve the clinical outcomes in nmCRPC patients at high risk of metastatic progression. The Expert Council was presented with the data of a registration clinical study on darolutamide efficacy and safety. The advantages of introducing this drug into clinical practice to expand the choice of therapeutic options were identified. Personalized adjustment of a treatment regimen will increase the treatment efficacy and ensure higher survival in this category of patients. Conclusion: Increasing survival as the main objective in treating nmCRPC patients requires improved diagnostics through regular controlling of testosterone and PSA levels, calculation of PSA doubling time, and the use of radiological diagnostic methods to rule out distant metastases. The choice of therapy in patients at high risk of metastasis shall consider the patient’s status and the treatment efficacy and safety balance.

Download Full-text

When should salvage radiation therapy be associated with concomitant hormonal therapy in patients affected by prostate cancer? The key role of PSA doubling time

European Urology Supplements ◽

10.1016/s1569-9056(18)33345-1 ◽

2018 ◽

Vol 17 (8) ◽

pp. 333-334

Author(s):

A. Briganti ◽

N. Fossati ◽

J. Karnes ◽

M. Soligo ◽

S. Boorjian ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Hormonal Therapy ◽

Doubling Time ◽

Salvage Radiation Therapy ◽

Psa Doubling Time

Download Full-text

Safety and Immunological Efficacy of a DNA Vaccine Encoding Prostatic Acid Phosphatase in Patients With Stage D0 Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.9968 ◽

2009 ◽

Vol 27 (25) ◽

pp. 4047-4054 ◽

Cited By ~ 169

Author(s):

Douglas G. McNeel ◽

Edward J. Dunphy ◽

James G. Davies ◽

Thomas P. Frye ◽

Laura E. Johnson ◽

...

Keyword(s):

Prostate Cancer ◽

T Cells ◽

Acid Phosphatase ◽

T Cell ◽

Dna Vaccine ◽

Cd8 T Cells ◽

Doubling Time ◽

Prostatic Acid Phosphatase ◽

T Cell Response ◽

Psa Doubling Time

Purpose Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer. Patients and Methods Twenty-two patients were treated in a dose-escalation trial with 100 μg, 500 μg, or 1,500 μg plasmid DNA, coadministered intradermally with 200 μg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment. Results No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFNγ-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054). Conclusion The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.

Download Full-text