Elsevier

Brachytherapy

Volume 19, Issue 3, May–June 2020, Pages 275-281
Brachytherapy

Prostate
Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation

Presented at the 2019 American Brachytherapy Annual Meeting in Miami.
https://doi.org/10.1016/j.brachy.2020.01.008Get rights and content

Abstract

Purpose

Men with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT).

Methods and Materials

Three hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan–Meier method with associations determined by log rank and Cox regression.

Results

Ten-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001).

Conclusions

Survival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.

Introduction

The successful treatment of prostate cancer depends on identifying men whose disease is detected when confined to the gland. Although men with low-risk cancers are increasingly being referred for active surveillance, those with intermediate- and high-risk disease are typically referred for definitive therapy. Surgery and radiation can be successful when Gleason grade Groups 2–4 are present but often fails in men with the highest grades, 9–10 or group 5 disease. These men often have disease that is resistant to standard doses of radiation or cancers that have spread outside of the gland.

Although radical prostatectomy may be considered the “gold standard” for localized prostate cancer, survival after surgery in men with Gleason Group 5 is inferior compared to those with lower grades. Bahler et al. reported on 119 men with high-grade cancer of which 80 had Gleason Group 5. Five-year prostate-specific antigen (PSA) freedom from relapse was 26% (1). Similarly, the use of external beam irradiation (EBRT) with hormone therapy has not proved to substantially improve these poor results. In an evaluation of 99 men, Narang et al. found similar inferior outcomes when very high-risk prostate cancer was present (2). At 10 years, 56.6% had biochemical failure and 13.2% had died of prostate cancer when conventional radiation doses were used.

Brachytherapy plus EBRT (combination therapy) delivers a higher dose of radiation than EBRT and provides these higher doses to a wider margin, which may improve results in men with extraprostatic disease. Many studies, where information was extracted from population-based data sets, have explored the advantages of combination therapy over EBRT and radical prostatectomy (3,4). In a 2017 report, an American Brachytherapy Society task group reviewed 39 publications in men with high-risk prostate cancer treated by RP, EBRT, and combination therapy (5). Ten-year biochemical relapse free survival ranged from 27 to 68% for RP, 37–55% for EBRT, and 54–93% for combination therapy. Although these studies suggest that combination therapy may improve survival compared to EBRT and radical prostatectomy, there are limitations to analyses that use nonprospective data.

We sought to define the biochemical failure-free rates, freedom from metastases, and cause-specific survival in a cohort of men with Gleason grade Group 4 and 5 disease from two institutions that have used combination therapy to treat high-grade prostate cancer for more than 25 years. We identified pretreatment and treatment-related variables that are associated with favorable outcomes and those with additional systemic therapy may warrant consideration.

Section snippets

Methods and materials

A total of 2742 men from Mount Sinai Hospital (MSH, New York, NY, n = 2277) and The Brachytherapy Center at Hygeia Hospital (HBC, Athens, Greece, n = 465) were enrolled in a prospective database for patients with prostate cancer treated by permanent seed implant. The combination therapy program began in 1993 at Mount Sinai and in 2000 at Hygeia Hospital. The data from both centers were deidentified and anonymized and combined into one database for the purposes of reporting oncologic and quality

Results

The median age, PSA, time on NHT, and BED were 69 years (range 39-88), 9.0 ng/mL (range 1-119), 9 months (range 0-36, 10 men did not receive NHT), and 210 Gy (range 47–261) (Table 1). Age was not different between men with GG 4 vs. 5 (p = 0.604). Ten-year FBF for GG 4 vs. 5 was 76.5 vs. 61.3% (p = 0.015); FFM was 93.5 vs. 83.8% (p = 0.006) and CSS was 94 vs. 79.3% (p = 0.001) (Fig. 1, Fig. 2, Fig. 3). Lower radiation dose was associated with greater biochemical failure (191.6 Gy, 95% CI

Discussion

Men with Gleason score 9–10 (grade Group 5) prostate cancer present a significant challenge if curative intent is intended. Although radical prostatectomy may be considered by some to be the gold standard for men with localized prostate cancer, surgical removal by itself has not been associated with a high success rate. Bahler et al. reported on 119 men with high-grade cancer of which 80 had Gleason Group 5. Five-year PSA-free relapse was 26% (1). Inman et al. identified 13 cases with Gleason

Conclusions

When found early, men with Gleason grade Group 4 and 5 prostate cancer have 10-year cause-specific survival >85%. A radiation dose with a BED ≥200 Gy should be delivered, which has a greater likelihood in eradication of local disease and decreasing the risk of systemic progression. A combination of BT plus EBRT can deliver these higher doses.

References (22)

Cited by (6)

  • Comparison of AUA and phoenix definitions of biochemical failure following permanent brachytherapy for prostate cancer

    2022, Brachytherapy
    Citation Excerpt :

    Brachytherapy is known to deliver higher doses of radiation to the prostate than standard external beam radiation therapy (EBRT) and lead to lower PSA nadirs (5). Higher doses of radiation and lower PSA nadirs are associated with a lower likelihood of local failure and a better CSS (6,7). Therefore, the ablative effect of brachytherapy, when delivered at a high biological equivalent dose (BED), may be akin to prostate gland removal and so the same PSA failure definition could be applied to both.

  • Detection of failure patterns using advanced imaging in patients with biochemical recurrence following low-dose-rate brachytherapy for prostate cancer

    2022, Brachytherapy
    Citation Excerpt :

    When delivered as monotherapy for low or favorable intermediate risk prostate cancer, long term efficacy is excellent (1–6). In patients with unfavorable intermediate risk and high-risk prostate cancer, the addition of brachytherapy to external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) results in superior biochemical control (1,7–10). Despite the overall efficacy of brachytherapy, a subset of patients treated with this modality will still develop biochemical failure, and require therapy for recurrent prostate cancer (11–13).

  • Pattern of Biopsy Gleason Grade Group 5 (4 + 5 vs 5 + 4 vs 5 + 5) Predicts Survival After Radical Prostatectomy or External Beam Radiation Therapy

    2022, European Urology Focus
    Citation Excerpt :

    Several studies have identified Gleason scores of 8–10 as predictors of poor survival and high risk of biochemical recurrence (BCR) among patients with prostate cancer [1–6]. Since the implementation of the five-tiered Gleason grade group (GG) scheme proposed by the International Society of Urological Pathology (ISUP), several studies have validated its discriminant properties regarding BCR and cancer-specific mortality (CSM) for patients treated with radical prostatectomy (RP) or external beam radiation therapy (EBRT) [7–14]. However, available patient observations were limited for the GG 5 subgroup [15–19].

Disclosures: There was no external funding supporting this investigation.

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