Prospective evaluation of quality of life after interstitial brachytherapy for localized prostate cancer

PURPOSE: Permanent interstitial brachytherapy (IB) has become an increasingly appealing therapeutic option for localized prostate cancer (LPC) among physicians and patients because it involves short hospitalization and treatment and its postulated low degree of toxicity may reduce its impact on the patients' quality of life (QoL). The aim of this prospective study was to assess the impact of IB on the QoL of patients with LPC. METHODS AND MATERIALS: A validated self-completed questionnaire was administered to the patients before and after IB and then at yearly intervals. The items allowed the identification of seven subscales exploring physical well-being (PHY), physical autonomy (POW), psychological well-being (PSY), relational life (REL), urinary function (URI), rectal function (REC), and sexual function (SEX). RESULTS: The assessment of the QoL of 147 patients treated between May 2000 and February 2005 revealed no relevant differences in the PHY scale scores 1 month after IB or later, and the same was true of the POW, PSY, and REL scales. Urinary function significantly worsened after IB and returned to pretreatment levels only after 3 years; the impact of the treatment on the URI scale was greater in the patients with good baseline urinary function than in those presenting more urinary symptoms before IB. Rectal and sexual functions were significantly worse only at the post-IB evaluation. CONCLUSIONS: The results of the present study confirm that the impact of IB on the patients' QoL is low despite its transient negative effects on some function, and extend existing knowledge concerning QoL after IB.     

Health-related quality of life after permanent I-125 brachytherapy and conformal external beam radiotherapy for prostate cancer - a matched-pair comparison

Background and purpose

The aim of the study was to compare quality of life after permanent I-125 brachytherapy (BT) and external beam radiotherapy (EBRT) for prostate cancer.

Materials and methods

A group of 104 patients (52 in each group) have been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT (70.2-72.0 Gy) or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs were matched according to the following criteria: age ±5years, prostate volume ±10 cc, use of antiandrogens, and erectile function.

Results

Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C; p < 0.05 for differences at times B/C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). No difference concerning erectile dysfunction was found (67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT at time C).

Conclusions

BT was associated with higher urinary, but lower rectal toxicity. The risk of treatment-associated erectile dysfunction did not differ between these methods.     

Patterns of failure after iodine-125 seed implantation for prostate cancer

Purpose

To determine the site of relapse when biochemical failure (BF) occurs after iodine-125 seed implantation for prostate cancer.

Materials and methods

From 2001–2009, 500 men underwent implantation in Wellington, New Zealand. Men who sustained BF were placed on relapse guidelines that delayed restaging and intervention until the prostate-specific antigen (PSA) was ?20 ng/mL.

Results

Most implants (86%) had a prostate D90 of ?90%, and multivariate analysis showed that this parameter was not a variable that affected the risk of BF. Of 21 BFs that occurred, the site of failure was discovered to be local in one case and distant in nine cases. Restaging failed to identify the site of relapse in two cases. In nine cases the trigger for restaging had not been reached.

Conclusions

If post-implant dosimetry is generally within the optimal range, distant rather than local failure appears to be the main cause of BF. Hormone treatment is therefore the most commonly indicated secondary treatment intervention (STI). Delaying the start of STI prevents the unnecessary treatment of men who undergo PSA ‘bounce’ and have PSA dynamics initially mimicking those of BF.     

Prostate brachytherapy in patients with prostate volumes ≥ 50 cm: dosimetic analysis of implant quality

Objectives: Permanent implantation with ¹²⁵I in patients with localized prostate cancer who have prostate volumes ≥ 50 cm³ is often technically difficult owing to pubic arch interference. The objective of this study was to describe dosimetry outcomes in a group of patients who were implanted using the real-time ultrasound-guided technique who had prostate volumes ≥ 50 cm³.

Materials and Methods: A total of 331 patients received an ¹²⁵I prostate seed implant from January 1, 1995, to June 1, 1999, of whom 66 (20%) had prostate volumes ≥ 50 cm³ at the time of the procedure. The real-time seed implant method was used in all patients and consisted of intraoperative planning and real-time seed placement using a combination of axial and sagittal ultrasound imaging. Pubic arch interference was managed using an extended lithotomy position or by angling the tip of the ultrasound probe in an anterior direction. No preimplant pubic arch CT scan study was performed and no patients were excluded from treatment because of prostate size. Implant quality was assessed using CT-based dosimetry performed 1 month postimplant. Dose–volume histograms for the prostate, bladder, rectum, and urethra volumes were generated. The target dose for these implants was 160 Gy and an adequate implant was defined as the dose delivered to 90% of the prostate (D90) ≥ 140 Gy. The dose delivered to 95% of the prostate (D95) and doses to 30% of the rectal (DRECT30) and urethral (DURE30) volumes were also calculated.

Results: Prostate volumes in the 66 patients ranged from 50 to 93 cm³ (median 57, mean 61 cm³). Total activity implanted was 27.8–89.1 mCi (median 57 mCi), with a range in activity per seed of 0.36–0.56 mCi (median 0.4 mCi). The prostate D90s and D95s ranged from 13,245 to 22,637 cGy (median 18,750) and 11,856 to 20,853 cGy (median 16,725), respectively. Only one patient (1.5%) had a D90 < 140 Gy. The DURE30 values ranged from 15,014 to 27,800 cGy (median 20,410) and the DRECT30 values were 3137–9910 cGy (median 5515).

Conclusion: Implantation of the large prostate can be accomplished using the real-time method. A total of 98.5% of the patients receive a high-quality implant. In addition, these implants should not put patients at increased risk for significant urinary and bowel complications because urethral and rectal doses can be kept at acceptable levels.     

Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: the University of California-San Francisco experience

PURPOSE: The aim of this study was to evaluate the feasibility and safety of salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer after external beam radiotherapy (EBRT). METHODS AND MATERIALS: We retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR brachytherapy for locally recurrent prostate cancer after EBRT between November 1998 and December 2005. After pathologic confirmation of locally recurrent disease, all patients were treated with 36 Gy in six fractions using two transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven patients received neoadjuvant hormonal therapy immediately presalvage, whereas none received adjuvant hormonal therapy postsalvage. Median follow-up time from recurrence was 18.7 months (range, 6-84 months). Determination of subsequent biochemical failure after brachytherapy was based on the definition by the American Society for Therapeutic Radiology and Oncology. RESULTS: Based on the Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three patients developed Grade 3 genitourinary toxicity. Maximum observed gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2-year Kaplan-Meier estimate of biochemical control after recurrence was 89%. Thirteen patients have achieved a PSA nadir < or =0.1 ng/ml, but at the time of writing this endpoint has not yet been reached for all patients. All patients are alive; however 2 have experienced biochemical failure, both with PSA nadirs > or =1, and have subsequently been found to have distant metastases. CONCLUSIONS: Salvage HDR prostate brachytherapy appears to be feasible and effective.     

Prospective evaluation of quality of life after permanent prostate brachytherapy with I-125: Importance of baseline symptoms and of prostate-V150

Background and purpose

Detailed knowledge of quality of life (QoL) after permanent I-125 brachytherapy may aid in counselling patients with early-stage prostate cancer.

Materials and methods

Seventy-four consecutive patients with low-risk prostate cancer were asked to complete the EORTC QLQ-C30 questionnaire with the prostate-specific PR25 module before implant, four weeks and one year after implant (response rates 97%, 88% and 89%, respectively). Implant characteristics were correlated with QoL scores.

Results

Global QoL was stable from pre-treatment to one year after implant and similar to age-adjusted scores of healthy controls. Significant changes versus baseline in QLQ-C30 domains were worsened social function at four weeks, increased constipation at four weeks and at one year and improved emotional function at one year. PR25 urinary symptoms were significantly increased at four weeks and, despite some improvement, at one year; bowel symptoms were slightly increased. Both types of symptoms were most strongly related with pre-treatment symptom scores. Prostate-V150 was the only implant parameter significantly associated with both urinary and bowel symptoms at four weeks and one year.

Conclusions

Limiting the high-dose subvolume in the prostate may be beneficial to reduce urinary and bowel symptoms but the major determinant of symptoms after I-125 implant is the baseline symptom level.     

A comparative study of quality of life in patients with localized prostate cancer treated at a single institution: Stereotactic ablative radiotherapy or external beam + high dose rate brachytherapy boost

PurposeTo compare the quality of life (QOL) in patients treated with stereotactic ablative radiation therapy (SABR) alone or high dose rate (HDR) brachytherapy + hypofractionated external beam radiotherapy (EBRT).Methods and materialsPatient self-reported QOL was prospectively measured among patients from two sequential phase 2 clinical trials: 1-SABR 35 Gy/5 fractions/5 weeks, 2–15 Gy HDR 1 fraction, followed by EBRT 37.5 Gy/15 fractions/3 weeks. The expanded prostate cancer index composite was assessed at baseline and q6 monthly up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5*standard deviation of the baseline for each domain. Fisher exact test and general linear mixed model were used (p < 0.05).Results84 and 123 patients were treated on the SABR and HDR boost studies, with a median follow up of 51 and 61 months respectively. There was a significant difference in MCIC between treatments in the urinary function and bother (p < 0.0001), the bowel function (p = 0.0216) and the sexual function (p = 0.0419) and bother (p = 0.0290) domains in favor of the SABR group. Of patients who reported no problem with their sexual function at baseline, 7% and 23% respectively considered it to be a moderate to big problem on follow up (p = 0.0077).ConclusionPatients treated with HDR-boost reported deterioration of QOL particularly in sexual domains in comparison with SABR.     

Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer

Purpose: To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI).

Methods and Materials: Between 1989–1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45–80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scores ≥7. The median pretreatment PSA was 7 ng/mL (range: 1–58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level was ≤10.0 ng/mL and Gleason score ≤6; those with one and two adverse prognostic features (PSA > 10 ng/mL and Gleason score >6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12–126 months).

Results: Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0.4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication.

Conclusions: Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.     

Focal salvage therapy for localized prostate cancer recurrence after external beam radiotherapy: A pilot study

BACKGROUND:

The objective of this study was to evaluate the safety, feasibility, side‐effect profile, and proof of concept for focal salvage therapy using high‐intensity focused ultrasound (HIFU).

METHODS:

A registry‐based analysis was conducted between 2004 and 2009 of 430 patients who underwent HIFU. Thirty‐nine patients received focal salvage therapy for localized recurrence after external beam radiotherapy. Multiparametric magnetic resonance imaging studies combined with transperineal template prostate mapping biopsies or transrectal biopsies were used to localize disease. Validated questionnaires were used to assess functional outcomes. Biochemical failure was defined by using both Phoenix criteria (prostate‐specific antigen [PSA] nadir plus 2 ng/mL) and Stuttgart criteria (PSA nadir plus 1.2 ng/mL).

RESULTS:

The mean pre‐HIFU PSA level was 4.6 ng/mL. The median follow‐up was 17 months (interquartile range, 10‐29 months). International Index of Erectile Function‐5 scores decreased from a median ± standard deviation (SD) of 18 ± 16 to 13 ± 21 at 6 months, demonstrating worsening function. Scores on the University of California Los Angeles‐Expanded Prostate Cancer Index Composite Urinary domain indicate that pad‐free, leak‐free continence status was 64%, and the pad‐free rate was 87.2% at last follow‐up. One rectourethral fistula occurred and spontaneously resolved with urinary and bowel diversion. The actuarial progression‐free survival rate (including PSA nonresponders) was 69% at 1 year and 49% at 2 years according to Phoenix criteria. Excluding PSA nonresponders, these rates were 74% and 58%, respectively (Phoenix criteria).

CONCLUSIONS:

The results from this study indicated that focal salvage therapy is a potential strategy for localized recurrence after radiotherapy that may reduce the harms resulting from whole‐gland salvage therapies. Cancer 2012. © 2011 American Cancer Society.     

Toxicity profile with a large prostate volume after external beam radiotherapy for localized prostate cancer

PURPOSE: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. METHODS AND MATERIALS: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm(3)) and a large (44-151 cm(3)) prostate volume. RESULTS: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm(3) vs. 47 cm(3); p < 0.01). CONCLUSIONS: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.     

High dose rate brachytherapy boost for prostate cancer: A systematic review

Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. “LDR-BT boost”) is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85–100%, 80–98%, 59–96%, and 34–85%, respectively. Late Radiation Therapy Oncology Group grade 3–4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk-stratification, expected outcomes, toxicities, quality of life, and cost.     

A modelled comparison of prostate cancer control rates after high-dose-rate brachytherapy (3145 multicentre patients) combined with,or in contrast to,external-beam radiotherapy

Background and purpose

To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combined external beam and high-dose-rate brachytherapy, in comparison with expected results using projections based on dose/fractionation/response parameter values deduced from a previous external-beam-alone 5969-patient multicentre dataset.

Material and methods

Results on a total of 3145 prostate cancer patients receiving brachytherapy (BT) as part or all of their treatment were collected from 10 institutions, and subjected to linear-quadratic (LQ) modelling of dose response and fractionation parameters.

Results

Treatments with BT components of less than 25 Gy, 3–4 BT fractions, doses per BT fraction up to 6 Gy, and treatment times of 3–7 weeks, all gave outcomes expected from LQ projections of the external-beam-alone data (α/β = 1.42 Gy). However, BT doses higher than 30 Gy, 1–2 fractions, 9 fractions (BT alone), doses per fraction of 9–15 Gy, and treatment in only 1 week (one example), gave local control levels lower than the expected levels by up to ∼35%.

Conclusions

There are various potential causes of the lower-than-projected control levels for some schedules of brachytherapy: it seems plausible that cold spots in the brachytherapy dose distribution may be contributory, and the applicability of the LQ model at high doses per fraction remains somewhat uncertain. The results of further trials may help elucidate the true benefit of hypofractionated high-dose-rate brachytherapy.     

Quality of life two years after radical prostatectomy, prostate brachytherapy or external beam radiotherapy for clinically localised prostate cancer: the Catalan Institute of Oncology/Bellvitge Hospital experience

Objective  The objective was to compare the short- and long-term impact of 3 different treatment modalities on health-related quality of life (HRQOL) in patients treated for localised prostate cancer at a single centre in Catalonia, Spain. Material and methods  This was a longitudinal, prospective study of 304 patients from a single centre in Catalonia, Spain. Patients underwent 1 of 3 treatment procedures: radical prostatectomy (114 patients), external beam radiation (134) or interstitial brachytherapy (56). HRQOL was assessed by both general and specific questionnaires, including the SF-36 health survey and the Expanded Prostate Cancer Index Composite (EPIC). Interviews were administered prior to treatment and at months 1, 3, 6, 12 and 24. One-way analysis of variance and generalised estimating equations models were constructed to assess between-group differences in HRQOL. Results  After initial deterioration, HRQOL scores partially recovered, although significant differences between treatment groups persisted at two years. Worsening of urinary incontinence was especially marked for the radical prostatectomy group (11.45, p=0.005), while deterioration in the urinary irritative/obstructive domain was worse following brachytherapy treatment (4.76, p=0.025). Decline in sexual function was significantly greater for the radical prostatectomy group than for the brachytherapy group (18.74, p<0.001). No significant between-group differences were observed in bowel domain scores. Conclusions  Quality of life 2 years after treatment for prostate cancer shows wide variability. Radical prostatectomy had the largest negative impact on the sexual and urinary incontinence domains. Differences between external radiation and brachytherapy were relatively small. Brachytherapy led to a moderate increase in urinary irritation compared to the other 2 groups.     

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy

Background and purpose

Initial results of Stereotactic Ablative Body Radiotherapy (SABR) in the treatment of localized prostate cancer appear promising however long-term quality of life (QOL) outcomes and dosimetric correlates are necessary.

Material and methods

A phase I/II study was performed where low risk prostate cancer patients received SABR 35 Gy in 5 fractions, once weekly. Patient self-reported QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC) at baseline and q6 month up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5 ∗ standard deviation of the baseline. Univariate and multivariate logistic regression were used to identify dosimetric predictors of MCIC.

Results

84 patients were included. The median follow-up was 50.8 months (interquartile range [IQR], 44.7–56.3). 17.9%, 26.2% and 37.5% of patients reported worse QOL on follow up in the urinary, bowel and sexual domains respectively. On univariate analysis Rectal V31.8 > 10%, D1cc > 35 Gy were associated with bowel MCIC, penile bulb (PB) V35 > 4%, V20 > 40% with sexual MCIC. Of these factors only rectal D1cc and PB V35 were predictors of worse QOL on multivariate analysis.

Conclusions

Long-term single-institution QOL outcomes are encouraging. Rigorous dosimetric constraints are needed to keep bothersome side effects low.