Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma

doi:10.1016/S0360-3016(99)00259-X

International Journal of Radiation OncologyBiologyPhysics

Volume 45, Issue 4, 1 November 1999, Pages 853-856

https://doi.org/10.1016/S0360-3016(99)00259-X Get rights and content

Abstract

Purpose: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (¹⁰³Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma.

Methods and Materials: One hundred twenty-four consecutive patients with Stage T2a–T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7–10 (40 patients), pretreatment prostate specific antigen (PSA) > 15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a ¹⁰³Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal < 4 ng/ml).

Results: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14).

Conclusion: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.

Introduction

Patients with early-stage prostate cancer who present with a serum prostate specific antigen (PSA) greater than 10 ng/ml or Gleason score above six are at high risk of cancer persistence after prostatectomy or radiation. There is a high likelihood of biochemical cancer persistence in such patients, regardless of treatment modality 1, 2, 3. While both PSA and Gleason score are strong predictors of recurrence, there is still a wide range of response to therapy within PSA or Gleason categories. Other factors might help to more precisely identify patients’ risk for recurrence.

Long before the introduction of PSA, prostatic acid phosphatase (PAP) was identified as an important prognostic indicator for prostatic carcinoma (4). Patients with an elevated pretreatment PAP were at such high risk of clinically evident failure after radical prostatectomy or radiation that they were classified “D0,” and were advised against prostatectomy 1, 4, 5. Assaying serum PAP was a standard part of the work-up for prostatic carcinoma until the introduction of PSA. Because of the greater sensitivity of PSA for detecting cancer and for monitoring residual prostate cancer after therapy, PSA rapidly replaced PAP as the most commonly used prostate tumor marker (6).

We have previously reported a strong influence of pretreatment PAP in patients treated with brachytherapy (7). This report is a detailed summary of the prognostic role of enzymatic PAP, with much longer follow-up than that reported for any treatment modality.

Section snippets

Methods

One hundred twenty-four consecutive patients with Stage T2a–T3 (American Joint Committee, 1992) prostatic carcinoma were treated from 1992 through 1995. No patients with Stage T1c disease are included because during that time, such patients were routinely treated only with radiation implant. Patient age ranged from 49 to 88 years (median 71). Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2c or greater (100 patients), Gleason score of 7

Results

There was little correlation between pretreatment PSA, Gleason score, or PAP (Fig. 1, Fig. 2, Fig. 3 ).

Twenty-six patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 4 years is 76%, with 28 patients followed beyond that time (Fig. 4). There were no clinically evident local failures, although routine follow-up prostate biopsies were not performed. Twenty-six patients received a short course (2 months) of pretreatment androgen ablation. Use of

Discussion

The cells and glands of prostatic carcinoma lose their normal functional and structural polarity. In contrast to the normal prostate, where most cell secretory products are secreted into the lumen of glands, the cells of prostate cancers secrete their products (PSA and PAP) into the stroma as well as into the lumen. More advanced tumors are more likely to secrete PAP and PSA into the stroma, where it can reach the general circulation. An elevated PAP correlates with a high likelihood of cancer

Acknowledgements

The authors thank Beatriz Dattoli for her assistance with data managment.

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It has been proved that an abnormally elevated level of ACP in the human body indicates onset of several diseases, such as metastasized prostate cancer [4], hyperparathyroidism [5], Gaucher’s disease [6], multiple myeloma [7] and enzyme disorders related to kidneys, veins, and bones [4]. Therefore, the precisely monitoring of ACP level in physiological media is of great significance for pathologic diagnosis, postsurgical evaluation and drug screening of these relative diseases [8, 9]. Clinically, the measurement of ACP activity has been used to diagnose cancers and monitor cell viability [10].
In this work, a convenient and effective fluorescent “Switch-On” nanosensor was developed for the sensitive and selective detection of acid phosphatase (ACP) activity based on nitrogen-doped carbon dots (N-CDs)-manganese dioxide (MnO₂) nanocomposites. Due to the formation of N-CDs-MnO₂ nanocomposites, the fluorescence of N-CDs could be greatly quenched by MnO₂ nanosheets through fluorescence resonance energy transfer (FRET). Upon the introduction of L-ascorbic acid (AA), MnO₂ nanosheets could be reduced to Mn²⁺ ions, which resulted in sufficient recovery of fluorescent signal. Thus, the ACP can be monitored based on the enzymatic hydrolysis of l-ascorbic acid-2-phosphate (AAP) by ACP to generate AA. The quantitative determination of ACP activity in the range of 5–40 U L⁻¹ with the detection limit of 0.1 U L⁻¹ can be achieved in this sensing system. Endowed with high sensitivity and selectivity, the developed nanosensor is capable of monitoring ACP level in human serum samples with satisfactory results, indicating its great potential to be used in clinical diagnosis.
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Improved implant quality with the ultrasound-guided approach has resulted in better biochemical relapse–free survival (BRFS) outcomes in several modern studies (7–9). Improved patient selection combined with improved implant quality, due to prostate specific antigen (PSA) screening and technical improvements in implantation, has led to brachytherapy reports that now consistently match or surpass the top surgical and EBRT BRFS outcomes (10–22). We report the long-term, 15-year BRFS, overall-survival (OS), and cause-specific survival (CSS) outcomes of the early Seattle experience with T1–T2 transperineal ultrasound-guided I125 permanent prostate implants (PPI) as monotherapy.
To report 15-year biochemical relapse–free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I¹²⁵ brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience.
Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I¹²⁵ monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots.
Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups.
I¹²⁵ monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.
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La braquiterapia prostática se ha consolidado en los últimos años como tratamiento de primera línea en pacientes seleccionados con cáncer de próstata localizado. Pretendemos realizar una actualización del tema.
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La braquiterapia prostática constituye una alternativa terapéutica en el cáncer de próstata localizado de bajo riesgo y en pacientes seleccionados de riesgo intermedio, con escasas complicaciones y una aceptable tasa de control bioquímico.
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Improved implant quality has been demonstrated to result in better biochemical relapse-free survival (BRFS) outcomes in several modern studies (6–8). Today’s improved patient selection and improved implant quality has resulted in multiple brachytherapy reports demonstrating 5–10 year BRFS rates are equivalent to the best published radical prostatectomy and three-dimensional conformal radiation therapy results (8–21). We report the Seattle 15-year results of transperineal interstitial permanent prostate brachytherapy combined with moderate-dose neoadjuvant EBRT in a group of consecutively treated and prospectively followed patients with clinical T1-T3 prostate cancer.
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Clinical InvestigationsPrognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgements

Int J Radiat Oncol Biol Phys

Urol Clin North Am

J Urol

Urol Clin North Am

Int J Radiat Oncol Biol Phys

J Urol

J Urol

J Urol

Clinical Investigations
Prognostic role of serum prostatic acid phosphatase for ¹⁰³Pd-based radiation for prostatic carcinoma