Transperineal interstitial permanent prostate brachytherapy for Japanese prostate cancer patients in Hawaii

BACKGROUND: Our aim was to report clinical and biochemical outcomes of transperineal interstitial permanent prostate brachytherapy in the treatment of Japanese patients with clinically organ-confined prostate cancer in Hawaii. METHODS: Ninety-five Japanese patients underwent transperineal interstitial permanent prostate brachytherapy using either iodine-125 or palladium-103 for clinical T1c-T2b N0 M0 prostate cancer. These procedures were carried out between December 1998 and December 2002 at The Queen's Medical Center in Honolulu, Hawaii. Prostate-specific antigen measurements were collected from all patients at follow up. Biochemical failure was defined by three consecutive rises in prostate-specific antigen levels, based on the criteria of the American Society for Therapeutic Radiology and Oncology Consensus panel. RESULTS: The median patient age was 71 years (range, 46-87 years). Thirty-six patients were implanted with either iodine-125 or palladium-103 as monotherapy; 59 patients received moderate-dose external beam irradiation first, followed by a prostate brachytherapy boost. The median follow-up length, calculated from the day of implantation, was 801 days (range, 237-1421 days). During this follow-up period, The Kaplan-Meier estimate of freedom from biochemical failure in this series was 94%. No major complications were observed. CONCLUSIONS: Clinical and biochemical outcomes in the treatment of Japanese patients in Hawaii suffering from localized prostate cancer, using transperineal interstitial permanent prostate brachytherapy, with or without external beam irradiation, compared favorably to results in similarly treated patients in the general US population.     

Contracted bladder developing after prostate brachytherapy

This report describes an extremely rare case of severely contracted bladder developing after prostate brachytherapy. In April 2001, a 76‐year‐old man initially presented to our hospital for weak urinary stream. The patient was diagnosed with and treated for benign prostatic hyperplasia. During follow up, prostate‐specific antigen level was elevated. In November 2005, the patient underwent transrectal prostate biopsy. Pathology showed adenocarcinoma, Gleason score 3 + 4 = 7. The patient was diagnosed with stage cT1cN0M0 prostate cancer. In January 2006, he underwent brachytherapy for prostate cancer. The procedure of brachytherapy was uneventful and the patient was discharged without any problems. Four months after the implant, the patient was admitted to our hospital for deterioration of kidney function as a result of a contracted bladder. Urinary culture of tuberculosis was negative and urinary cytology was class II. A urethral catheter was indwelled and the patient has been followed every month for catheter replacement. Bladder capacity is now less than 5 mL.     

Oncological impact of neoadjuvant hormonal therapy on permanent iodine‐125 seed brachytherapy in patients with low‐ and intermediate‐risk prostate cancer

Objectives

To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy.

Methods

Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography‐guided permanent iodine‐125 seed brachytherapy. We retrospectively analyzed low‐ or intermediate‐risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence‐free survival, progression‐free survival, cancer‐specific survival and overall survival.

Results

A total of 484 patients with low‐risk (259 patients) or intermediate‐risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5‐year actuarial biochemical recurrence‐free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence‐free survival outcomes in low‐ (P = 0.8949) or intermediate‐risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate‐specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence‐free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression‐free survival, cancer‐specific survival or overall survival.

Conclusions

In patients with low‐ or intermediate‐risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.     

Urinary morbidity after 125I brachytherapy of the prostate

OBJECTIVE: To assess urinary morbidity within the first 6 months after transperineal prostate brachytherapy (TPBT) with 125I for localized prostate adenocarcinoma. PATIENTS AND METHODS: Between September 2000 and July 2001, 50 consecutive patients with favourable early-stage prostate cancer were treated with TPBT. Clinical and objective investigations, including uroflowmetry and postvoid residual urine measurements, were evaluated for short-term urinary morbidity; predictive factors were also sought. RESULTS: Thirty-eight (76%) patients developed urinary disorders, but severe urinary complications were exceptional. The International Prostate Symptom Score (IPSS) changed significantly during the first and third month after implantation and then improved during the sixth month. Concomitantly, the maximum and the average urinary flow rate deteriorated significantly. The variations in postvoid residual were less significant. An initial IPSS of > 8 and previous alpha-blocker treatment were identified as significant predictive factors of urinary morbidity, as were the TPBT dose received by 90% of the target volume and by 30% of the urethra, and the volume of prostate receiving 144 Gy. CONCLUSION: Urinary morbidity after TPBT is frequent but rarely exceptionally severe; patients must therefore be given full information. Patients with a higher initial IPSS or having had previous alpha-blocker treatment, with their associated dosimetric factors, are at greater risk of these urinary morbidity.     

Impact of pre‐implant lower urinary tract symptoms on postoperative urinary morbidity after permanent prostate brachytherapy

Objectives: To assess the impact of baseline lower urinary tract symptoms on postoperative urinary morbidity in patients being treated for prostate cancer with 125‐I permanent prostate brachytherapy. Methods: A total of 104 prostate cancer patients were enrolled in this study. Their urinary morbidity was followed up using the International Prostate Symptom Score and Expanded Prostate Cancer Index Composite for 12 months or more after permanent prostate brachytherapy. Patients were classified into two groups based on their baseline International Prostate Symptom Score: the low International Prostate Symptom Score group (score ≤ 7) and the high International Prostate Symptom Score group (score ≥ 8). Urinary morbidity was estimated in each group based on the results of the International Prostate Symptom Score and Expanded Prostate Cancer Index Composite measured before permanent prostate brachytherapy, and at 1, 3, 6, 9 and 12 months after the end of all radiation therapy. Results: The overall mean total International Prostate Symptom Score, International Prostate Symptom Score quality of life score, and urinary‐related scores for Expanded Prostate Cancer Index Composite were significantly worse at 1 month after the end of treatment, but they improved gradually after the treatment and recovered to the baseline level within 12 months. Even in the high‐International Prostate Symptom Score group, the International Prostate Symptom Score and International Prostate Symptom Score Quality of Life score were significantly worse at 1–3 months after permanent prostate brachytherapy, and then recovered to the baseline level without prolongation. Although the urination‐related Expanded Prostate Cancer Index Composite score in the high‐International Prostate Symptom Score group was significantly worse at 1 month after permanent prostate brachytherapy in comparison with that in the low‐International Prostate Symptom Score group, it recovered to the baseline level without prolongation. Conclusions: The present findings suggest that the presence of lower urinary tract symptoms before implantation does not prolong urinary morbidity after permanent prostate brachytherapy.     

Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy

OBJECTIVE: To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0-7), moderate (8-19) and severe (>20) categories, predicts brachytherapy-related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherapy. PATIENTS AND METHODS: From January 1998 to September 2003, 1034 consecutive patients had permanent interstitial brachytherapy for clinical stage T1b-T3a NXM0 (2002 system) prostate cancer. Of the 1034 patients, 739 (71.5%) presented with an IPSS of 0-7, 287 (27.7%) of 8-19, and eight (0.8%) of > or = 20. The IPSS 8-19 cohort was further stratified into 8-14 (237 men) and 15-19 (50 men) subgroups. The median follow-up was 38.2 months. In all patients, an alpha-blocker was initiated before brachytherapy and continued at least until the IPSS normalized, the latter defined as a return to within 1 point of that before implantation. A median of 21 IPSS questionnaires were obtained per patient. Several clinical, treatment and dosimetric variables were evaluated as predictors of urinary morbidity. RESULTS: For the entire cohort, the IPSS peaked at a mean of 0.5 months after implantation and resolved at a mean of 1.7 months. At 5 years after brachytherapy, 90.1% of patients at risk (88.8%, 95.5%, and four of eight patients with a pre-implant IPSS of 0-7, 8-19 and > or = 20, respectively) were within the IPSS 0-7 category. Compared to the pre-implant IPSS, 13 patients (8%) were assigned to a higher IPSS severity category. Neither prolonged urinary catheter dependency (>5 days; 16 patients, 1.5%) or transurethral resection of the prostate (TURP, 17 patients, 1.6%) depended on the pre-implant IPSS subgroup. In Cox regression analysis, IPSS resolution was best predicted by pre-implant IPSS, prolonged catheter dependency by patient age, and TURP by any catheter dependency, the maximum IPSS increase and the maximum urethral dose. CONCLUSIONS: The IPSS before implantation predicted the resolution of IPSS after brachytherapy, but did not correlate with substantial urinary morbidity, including catheter dependency or the need for TURP. At 5 years after brachytherapy, 90.1% of patients at risk were assigned to the IPSS 0-7 category.     

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

OBJECTIVE

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.

PATIENTS AND METHODS

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).

RESULTS

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 ≤T2 with negative transrectal ultrasonography and/or magnetic resonance spectroscopy. The original Gleason score was ≤6 in nine patients, 7 in eight and ≥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.

CONCLUSION

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.     

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy

Study Type – Prognosis (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Cardiovascular disease is a leading cause of death in prostate cancer patients. Pretreatment ED is a surrogate for vascular pathology. Aggressive treatment of medical co‐morbidity in prostate cancer patients may positively impact overall survival.

OBJECTIVE

• ? To evaluate the relationship between pre‐treatment erectile function and all‐cause mortality in patients with prostate cancer treated with brachytherapy.

PATIENTS AND METHODS

• ? In all, 1279 consecutive patients with clinically localized prostate cancer and pre‐implant erectile function assessed by the International Index of Erectile Function‐6 (IIEF‐6) underwent brachytherapy.
• ? Potency was defined as an IIEF‐6 score of ≥13 without pharmacological or mechanical support.
• ? Patients were stratified into IIEF‐6‐score cohorts (≤12, 13–23 and 24–30).
• ? The median follow‐up was 5.0 years.

RESULTS

• ? The 8‐year overall survival (OS) of the study population was 85.1%.
• ? The 8‐year OS for IIEF‐6scores ≤12, 13–23 and 24–30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001).
• ? Cardiovascular events accounted for a significant portion of deaths in each IIEF‐6 group.
• ? When combined with other risk factors for cardiovascular disease, an IIEF‐6 score of ≤12 had an additive effect on all‐cause mortality (IIEF‐6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%).

CONCLUSIONS

• ? A pre‐implant IIEF‐6score of ≤12 was associated with a higher incidence of all‐cause mortality.
• ? Pre‐treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients.
• ? Aggressive treatment of medical co‐morbidity is warranted to impactOS.

     

Corticosteroid use after prostate brachytherapy reduces the risk of acute urinary retention

OBJECTIVES: To evaluate the role of short-term steroids after prostate brachytherapy to reduce oedema and thus the risk of urinary retention associated with brachytherapy, as this can require surgical intervention and may even result in incontinence. PATIENTS AND METHODS: A retrospective review was conducted on 400 consecutive patients with early-stage prostate cancer who underwent ultrasonography-guided transperineal brachytherapy. Androgen deprivation was given to 146 patients for 3 months before the implant and 280 received a 2-week course of dexamethasone (4 mg twice daily for 1 week then 2 mg twice daily). Forty-five patients developed acute urinary retention at a median of 12 days after implantation. Univariate and multivariate analyses were used to evaluate the potential risk factors for urinary retention. RESULTS: Acute urinary retention developed in 11.1% of the patients and the risk was predicted by increasing prostate volume at the time of diagnosis. This risk was higher (18.8%) for men receiving no dexamethasone and lower (8.2%) for those who did. In the multivariate analysis the volume at diagnosis and the use of dexamethasone remained significant. The use of steroids counterbalanced the effect of increasing prostate volume on the incidence of retention. The risk of retention was higher in those men receiving androgen deprivation to shrink their prostates than in those whose prostates were of suitable size for implantation at the time of diagnosis. CONCLUSION: Reducing prostate volume by androgen deprivation before brachytherapy may be less important in preventing brachytherapy-related urinary retention than the use of corticosteroids to reduce oedema afterward.     

The pathophysiology of lower urinary tract symptoms after brachytherapy for prostate cancer

OBJECTIVES: To determine the spectrum of pathophysiology underlying the lower urinary tract symptoms (LUTS) persisting for > or = 6 months after brachytherapy for localized prostate cancer. PATIENTS AND METHODS: A database of men from two practice settings was searched for men who developed LUTS persisting for > or = 6 months after completing brachytherapy for localized prostate cancer. Patients were evaluated with a structured history and physical examination, International Prostate Symptom Score (IPSS), 24-h voiding diary, noninvasive free-flow uroflowmetry, postvoid residual urine volume (PVR), cystoscopy and a video-urodynamic study. Specific data collected included symptoms, elapsed time since brachytherapy, Gleason score, IPSS, total number of voids/24 h, maximum voided volume, cystoscopic findings, and urodynamics findings (PVR, maximum urinary flow rate, Schaefer obstruction grade, Watts factor, incidence of detrusor overactivity (DO) urethral obstruction and low bladder compliance). These data were compared with those from a previous study of men with LUTS who did not have prostate cancer. RESULTS: The study included 47 men (aged 54-88 years); the median (range) interval between brachytherapy and evaluation was 1.5 (0.5-13) years. Thirty-seven men complained of overactive bladder symptoms (79%), and 31 of incontinence (71%), 21 of obstructive symptoms (44%), and persistent dysuria in 12 (26%). Comparison of urodynamic findings in men with unselected causes of LUTS vs LUTS due to brachytherapy revealed the following comparisons: DO in 252 of 541 (47%) unselected vs 28 of 33 (85%) brachytherapy, (P < 0.001); and urethral obstruction in 374 of 541 (69%) unselected vs 24 of 33 (73%) brachytherapy (P = 0.85). CONCLUSION: The pathophysiology and severity of persistent LUTS in men after brachytherapy differs from that of men with LUTS in the general population. Men after brachytherapy have a much higher incidence of DO, prostatic and urethral strictures and prostatic urethral stones.     

Survival after prostate brachytherapy in patients aged 60 years and younger

Study Type – Aetiology (prospective cohort) Level of Evidence 2B

OBJECTIVE

? To compare survival after prostate brachytherapy in patients aged ≤60 years with patients aged >60 years.

patientS AND METHODS

? We analysed 419 locally confined prostate cancer patients, treated between 1989 and 2001 with I‐125 implantation monotherapy. ? Endpoints were biochemical failure (BF) according to the +2 ng/mL definition, disease‐specific and overall survival. ? Patients were subdivided into age ≤60 years and age >60 years. ? Cox proportional‐hazards regression analyses were performed to study the independent effect of age on BF and disease‐specific survival.

RESULTS

? The younger cohort consisted of 87 patients (21%), with smaller prostate volumes and a lower average prostate cancer risk class than the older cohort, consisting of 332 patients (79%). Mean follow‐up was 9.1 years (±sd 2.8) for the younger cohort and 8.3 years (±sd 2.9) for the older cohort. ? The 10‐year (95% CI) freedom from BF, disease‐specific survival and overall survival rates were 63% (51–75), 87% (78–96) and 81% (69–89), respectively, for the younger cohort and 46% (39–54), 83% (78–89) and 60% (54–66), respectively, for the older patient cohort. ? Although a trend for better freedom from BF and disease‐specific survival was observed in younger patients, the difference proved not clinically significant.

CONCLUSION

? Prostate cancer risk group and the year of treatment relate to outcome, but not age. With respect to prostate cancer curability, there seems no objection to offer brachytherapy to patients aged 60 years and younger.     

High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after external beam radiation, brachytherapy or proton therapy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Salvage HIFU is a promising treatment option for local recurrence after radiation therapy, with morbidity comparable with other forms of salvage treatment. This study showed a long‐term follow up of salvage HIFU in men with recurrence of localized prostate cancer following not only external beam radiation therapy but also brachytherapy or proton therapy.

OBJECTIVE

To investigate the use of high‐intensity focused ultrasound (HIFU) as a salvage therapy in patients with recurrence of localized prostate cancer after external beam radiation (EBRT), brachytherapy, or proton therapy.

PATIENTS AND METHODS

We retrospectively reviewed the charts of all patients who had undergone salvage HIFU for biopsy‐proven prostate cancer after primary radiation therapy. Patient characteristics and oncological outcomes were assessed.

RESULTS

Records of 22 patients with a median (range) follow‐up of 24 (5–80) months were reviewed. Patients were men with presumed organ‐confined disease who had been treated with salvage HIFU following recurrent disease after EBRT (fourteen patients), brachytherapy (five patients: four with high‐dose brachytherapy using In¹⁹²; and one with low‐dose brachytherapy using Au⁹⁸) or proton therapy (three patients). The median (range) age at salvage HIFU was 65 (52–80) years, with a median (range) prostate‐specific antigen (PSA) level before radiation therapy of 14.3 (5.7–118) ng/mL and a median (range) PSA level of 4.0 (1.2–30.1) ng/mL before HIFU. The median (range) period to HIFU after radiation therapy was 36 (4–96) months. The biochemical disease‐free survival (bDFS) rate in all patients at 5 years was 52%. Rates of bDFS in low‐, intermediate‐ and high‐risk groups were 100%, 86%, and 14%, respectively. One of the twelve patients who received post‐HIFU prostate biopsy showed malignancy. Side effects included urethral stricture in four patients, grade I urinary incontinence in four patients, rectourethral fistula and epididymitis in one of each patient.

CONCLUSION

Salvage HIFU is a promising treatment option for local recurrence after radiation therapy, with morbidity comparable with other forms of salvage treatment.