Do patients with low-risk and intermediate-risk prostate cancer benefit from androgen deprivation?

216 Background: Prostate cancer is a common condition with varied pathologies based on stage, grade and presenting PSA allowing non-metastatic cases to be risk stratified at presentation. There is an evidence base for the use of Androgen Deprivation Therapy (ADT) combined with radical radiation showing a survival benefit but with an increase in patient morbidity. Prostate cancer risk stratification can be used to guide ADT therapy duration to reduce toxicity but it is unknown how closely these guidelines are followed internationally. Methods: A cross sectional survey collecting data on 15,255 patients with prostate cancer was conducted across 5 European countries and Japan. Data was interrogated to provide real-world evidence for ADT prescribing in combination with radical radiotherapy treatment and compared against the available evidence base and international best practice guidelines. Results: 3,393 patients were included in data analysis; 53% were high risk, 35% intermediate, and 12% low risk cases. 48% of patients were ages 71-80yrs with 10% being aged over 80. Data, including proposed length of hormone treatment was available for 2,832 patients. Concordance to the evidence base was good for high- and low-risk prostate cancer patients (64% and 96% respectively) but there was more disparity in the intermediate risk group with a concordance rate of only 28%. Conclusions: The data was robust enough to be interrogated and produce meaningful results. Concordance to the evidence base was high in both high and low risk disease although there was a tendency towards over-treatment in both these groups in some of the countries included. There was significant disparity in the intermediate risk group with evidence of both over- and potential under-treatment across all countries. Any potential over treatment with ADT needs to take account of the known evidence base and the potential for bone and metabolic toxicities. The data suggests that guidelines offering greater clarity on the role of ADT in intermediate risk prostate cancer may be beneficial.

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Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer

Cancer ◽

10.1002/cncr.30049 ◽

2016 ◽

Vol 122 (15) ◽

pp. 2341-2349 ◽

Cited By ~ 10

Author(s):

Aaron D. Falchook ◽

Ramsankar Basak ◽

Jahan J. Mohiuddin ◽

Ronald C. Chen

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation ◽

Intermediate Risk ◽

Risk Prostate Cancer

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Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer

Cancer ◽

10.1002/cncr.27911 ◽

2012 ◽

Vol 119 (8) ◽

pp. 1537-1546 ◽

Cited By ~ 74

Author(s):

W. James Morris ◽

Mira Keyes ◽

Ingrid Spadinger ◽

Winkle Kwan ◽

Mitchell Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Dose Rate ◽

Low Dose ◽

Population Based ◽

Low Risk ◽

Oncologic Outcomes ◽

Intermediate Risk ◽

Low Dose Rate ◽

Risk Prostate Cancer ◽

Low Dose Rate Brachytherapy

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Prostate Cancer Grade and Stage Misclassification in Active Surveillance Candidates: Black Versus White Patients

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2020.7580 ◽

2020 ◽

Vol 18 (11) ◽

pp. 1492-1499

Author(s):

Lara Franziska Stolzenbach ◽

Giuseppe Rosiello ◽

Angela Pecoraro ◽

Carlotta Palumbo ◽

Stefano Luzzago ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Temporal Trend ◽

Low Risk ◽

Intermediate Risk ◽

Multivariate Logistic Regression ◽

Black Patients ◽

Risk Prostate Cancer ◽

Misclassification Rates ◽

White Patients

Background: Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void. Methods: Within the SEER database (2010–2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used. Results: Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; P<.001) in those with very low risk, 48.6% versus 46.0% (absolute Δ = +2.6%; P<.001) in those with low risk, and 33.8% versus 35.3% (absolute Δ = –1.5%; P=.05) in those with favorable intermediate risk. Conclusions: Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.

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Phase 2b trial results of padeliporfin (WST11 or Tookad) vascular-targeted photodynamic therapy for partial gland ablation in men with intermediate-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17006 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17006-e17006

Author(s):

Jonathan Coleman ◽

Daniel D. Sjoberg ◽

Quinlan Demac ◽

Catriona ODea ◽

Marlena McGill ◽

...

Keyword(s):

Prostate Cancer ◽

Primary Endpoint ◽

Low Risk ◽

Gleason Grade ◽

Intermediate Risk ◽

Function Score ◽

Trus Biopsy ◽

Risk Prostate Cancer ◽

Partial Gland Ablation ◽

Targeted Photodynamic Therapy

e17006 Background: Padeliporfin (WST11) vascular-targeted photodynamic therapy (VTP) has shown significant clinical benefit as a localized partial gland ablation (PGA) therapy when compared to active surveillance for low-risk prostate cancer, by curbing progression and the need for radical treatment, leading to its regulatory approval in Europe. This phase 2b trial prospectively investigated WST11-VTP for intermediate-risk cancers. Methods: Men with unilateral Grade Group 2 (GG2) cancers (Gleason 3+4), evaluated with MRI and ultrasound-guided (TRUS) biopsy, underwent up to two WST11-VTP PGA sessions. Eligibility criteria included <cT2b, PSA < 10, and fusion biopsy for PIRADS 3+ lesions on pretreatment MRI. Contralateral very low–risk disease was observed. The primary endpoint was prevalence of any Gleason Grade 4 or 5 (≥GG2) cancer, determined by MRI and systematic, 14-core TRUS biopsy of the entire gland (+/- fusion) at 3 and 12 months after treatment. Treatment safety and patient-reported quality of life for sexual and urinary function were assessed with validated questionnaires (IIEF-15 and IPSS, respectively). The study was powered using β = 0.2 to reject the null hypothesis (r≤70%), using a one-sided exact binomial test with 5% alpha risk. To be valid, 44 evaluable patients were required for the 12-month primary endpoint assessment. Results: Of the 50 men treated, 46 were evaluable for the 12-month primary endpoint. Before 12 months, 1 man proceeded to prostatectomy (treatment failure), 2 men refused 12-month biopsy, and 1 man died of COVID-19. At 3 months, 12/49 (24%) men underwent per protocol second WST11-VTP PGA session for GG2 tumor: 9 for residual cancer and 4 for newly identified contralateral GG2 tumors (1 bilateral). The 12-month biopsy was performed in 45 men; 38 (83%) had no Gleason grade 4 or 5 cancer, including 11/12 (92%) patients who underwent 2 PGA sessions. By 3 months, median decline in erectile function score (IIEF-5) from baseline was -1.0 (IQR -7,0). Median improvement in urinary function score (IPSS) was -1.0 (IQR -1,5), with pad-free continence observed in all patients. Median change in IIEF score by 12-months was -1.0 (IQR -5,0). Grade 3 treatment-related adverse events occurred in 6 (12%) patients. All procedure-related prostate/pelvic pain resolved by 3 weeks. Conclusions: The positive results from this trial show that WST11-VTP is effective for PGA of intermediate-risk prostate cancer, with minimal toxicity or impact on urinary and sexual function, consistent with the phase 3 trial results in low-risk disease. Based on these data, this therapy bears consideration for approval as a conservative therapeutic option for selected cases of intermediate-risk disease. Clinical trial information: NCT03315754.

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