Salvage permanent perineal radioactive-seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy

Department of Urology, University of California, San Francisco, CA 94117, USA.
BJU International (Impact Factor: 3.53). 02/2009; 104(5):600-4. DOI: 10.1111/j.1464-410X.2009.08445.x
Source: PubMed


To assess our experience with salvage permanent perineal radioactive-seed implantation (SPPI) as a possible therapeutic option for recurrent prostate adenocarcinoma, as salvage therapies for recurrences after definitive external beam radiotherapy (EBRT) for localized adenocarcinoma of the prostate are associated with significant morbidity and biochemical failure.
We retrospectively analysed on patients who had SPPI for localized recurrent prostate adenocarcinoma from 1996 to 2007 after primary treatment with EBRT. Excluded were patients who had other primary treatment or had no follow-up. Primary outcomes were time to biochemical relapse-free survival, using the Phoenix definition of a prostate-specific antigen (PSA) nadir +2 ng/mL, and cancer-specific survival. Secondary outcomes were the International Prostate Symptom Score (IPSS), the International Index of Erectile Function-5 score (IIEF-5), and complications based on Common Terminology Criteria for Adverse Events (version 3).
In all, 37 patients had SPPI during this period; after applying inclusion and exclusion criteria, 24 remained for analysis. At the time of salvage therapy, the median time to the diagnosis of local recurrence was 49 months, the median PSA level was 3.36 ng/mL, the median PSA doubling time was 20 months, and all patients were clinically re-staged at <or=T2 with negative transrectal ultrasonography and/or magnetic resonance spectroscopy. The original Gleason score was <or=6 in nine patients, 7 in eight and >or=8 in three (not recorded in two). The median follow-up after SPPI was 30 months; the cancer-free survival was 96% (one death) and biochemical relapse-free survival was 88% (three patients). The PSA level was higher than the levels before SPPI at 3 months in all three failures, but lower in all 21 patients considered relapse-free. Complications included one urethral stricture, one grade 3 rectal haemorrhage and five grade 2 gross haematuria that resolved with conservative management. Insufficient data were available to assess the IPSS or IIEF-5 scores.
With a short-term follow-up SPPI appears to provide excellent prostate cancer control with an acceptable rate of complications for patients with local recurrence of prostate cancer after EBRT. An extended follow-up is necessary to determine the long-term durability and safety of SPPI.

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Available from: I-Chow Hsu, Oct 27, 2014
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    • "References Type of prostate brachytherapy Salvage dose prescription Primary treatment (EBRT/ brachytherapy) Primary radiation dose prescription Median (range) Follow-up (months) Biochemical control Late toxicity Beyer et al. (1999) [22] LDR whole gland 88% 125 I: 120 Gy 22% 103 Pd: 90 Gy Activity: NR 17 (17/0) 63.6 Gy (NR) 62 53% (5 years) GU: 24% incontinence GI: 0 Grado et al. (1999) [24] LDR whole gland 76% 103 Pd: 120 Gy (range 80 to 180), 24% 125 I: 160 Gy (range 80 to 180) Activity: NR 49 (46/3) 66.2 Gy (range 20.0–70.2) 64 34% (5 years) GU: 4% hematuria 6% painful penile dysuria GI: 4% rectal ulcers 2% colostomy Allen et al. (2007) [21] LDR whole gland 125 I: 109–112.5 Gy 103 Pd: 90–97 Gy Activity: NR 12 (12/0) 70 Gy (range, 59.4–70.2) 45 63% (4 years) GU: 16% grade 2 incontinence 8% grade 1 hematuria GI: 0 Nguyen et al. (2007) [73] LDR partial gland 125 I: 137 Gy Activity: 0.40 mCi/seed 25 (13/12) EBRT: (66–70.2) Brachytherapy: 137 Gy; MRI-guided 47 70% (4 years) GI: 8% Argon for proctitis GU: 8% 12% fistula Lee et al. (2007) [74] HDR whole gland 36 Gy/6fractions 21 (21/0) EBRT 72 Gy (63–78) 19 89% (2 years) GU: 14% grade 3/0 grade 4 GI: 0 grade 3/grade 4 Aaronson et al. (2009) [20] LDR whole gland + SIB 108 Gy whole gland + 144 Gy focal boost Activity: 13.32 MBq/seed 24 (24/0) EBRT 72 Gy (65–80) 30 89.5% (3 years) GU: 1 grade 3 hematochezia/0 grade 4 GI: 0 grade 3/0 grade 4 Burri et al. (2010) [23] "
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    ABSTRACT: Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.
    Cancer/Radiothérapie 09/2014; 18(5-6). DOI:10.1016/j.canrad.2014.07.153 · 1.41 Impact Factor
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    • "Actually, there is not prospectively data available in QoL in patients treated with salvage treatment. Most of data reported are based on functional outcomes instead of validated QoL instruments [10,11]. "
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    ABSTRACT: Purpose: To evaluate efficacy and toxicity after salvage brachytherapy (BT) in prostate local recurrence after radiation therapy. Methods and materials: Between 1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts) undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose levels according to biological equivalent doses (BED(2 Gy)). By the time of salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses were performed to identify predictors of biochemical control and toxicities. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCv3.0). Results: Median follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre-salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses BED(2 Gy) level < 227 Gy (p = 0.012) were significant in predicting biochemical failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were significant in predicting biochemical failure. HDR-BT BED(2 Gy) (α/β 1.5 Gy) levels ≥ 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting grade ≥ 2 urinary toxicity. Conclusions: Prostate BT is an effective salvage modality in some selected prostate local recurrence patients after radiation therapy. Even, we provide some potential predictors of biochemical control and toxicity for prostate salvage BT, further investigation is recommended.
    Radiation Oncology 04/2014; 9(1):102. DOI:10.1186/1748-717X-9-102 · 2.55 Impact Factor
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    ABSTRACT: What's known on the subject? and What does the study add? The curative treatment of prostate cancer includes surgery, external beam radiation or interstitial radiation. However, a high percentage of patients may develop recurrent disease, which is often localised. The possibilities of treatment in these cases, including surgery or adjuvant radiotherapy, are not well defined. Brachytherapy is a well established first-line treatment option. We review and update the use of brachytherapy in the treatment of recurrences post-radiotherapy, brachytherapy or radical prostatectomy as an alternative to surgery and radiotherapy, with a focus on functional and oncological outcomes. Salvage therapeutic options following radical prostatectomy or radiotherapy for patients with local relapse of prostate cancer include radical prostatectomy, radiotherapy, brachytherapy or cryotherapy. Salvage radical prostatectomy following radiotherapy failure is associated with a 5-year PSA relapse-free rate of 30–40%. Biochemical relapse-free survival rates after salvage radiotherapy following radical prostatectomy failure range from 10% to 77% after a follow-up of 22–60 months. A number of studies have evaluated salvage brachytherapy for radiotherapy failure and 5-year biochemical disease-free survival (bDFS) rate results reported are of the order of 20–87%; one study reported a 10-year bDFS rate of 54%. Fewer studies in small numbers of patients and with shorter follow-up have been conducted on brachytherapy for radical prostatectomy failure and bDFS rates reported include 25.8% at a median of 29 months to 70% at a median of 20 months. The side-effects were as expected for brachytherapy. A newer initiative conducted in Spain in a larger series of 42 patients with failure following radical prostatectomy involves brachytherapy with RAPID Strand™125I seeds and real-time placement. The 5-year bDFS rate was 88.6% and cancer-specific survival was 97%; complication rates were low. Optimization of salvage brachytherapy is under way and involves accurate placement of seeds, dose optimization and optimal patient selection.
    BJU International 02/2012; 109 Suppl 1(s1):17-21. DOI:10.1111/j.1464-410X.2011.10826.x · 3.53 Impact Factor
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