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Comparison of Health-Related Quality of Life 5 Years After SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial
Abstract and Figures
The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy (RP) and brachytherapy (BT) closed after 2 years due to poor accrual. We report health-related quality of life (HRQOL) at a mean of 5.3 years for 168 trial-eligible men who either chose or were randomly assigned to RP or BT following a multidisciplinary educational session.
After initial lack of accrual, a multidisciplinary educational session was introduced for eligible patients. In all, 263 men attended 47 sessions. Of those, 34 consented to random assignment, 62 chose RP, and 94 chose BT. Five years later, these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Expanded Prostate Cancer Index Composite, the Short Form 12 Physical Component Score, and Short Form 12 Mental Component Score. Response rate was 88.4%. The Wilcoxon rank sum test was used to compare summary scores between the two interventions.
Of 168 survey responders, 60.7% had BT (9.5% randomly assigned) and 39.3% had RP (9.5% randomly assigned). Median age was 61.4 years for BT and 59.4 for RP (P = .05). Median follow-up was 5.2 years (range, 3.2 to 6.5 years). For BT versus RP, there was no difference in bowel or hormonal domains, but men treated with BT scored better in urinary (91.8 v 88.1; P = .02) and sexual (52.5 v 39.2; P = .001) domains, and in patient satisfaction (93.6 v 76.9; P < .001).
Although treatment allocation was random in only 19%, all patients received identical information in a multidisciplinary setting before selecting RP, BT, or random assignment. HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction.
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... RP is generally associated with fewer acute gastrointestinal (GI) and obstructive urinary symptoms, whereas RT results in less urinary incontinence and erectile dysfunction. 9,10 Despite an improvement in biochemical recurrence (BCR), brachytherapy boost is associated with increased rates of toxicity, and improvements in BCR have not translated into survival advantages. 11 To date, it is unknown how these increased rates of toxicity affect the overall cost effectiveness of this treatment paradigm. ...
... EBRT with LDR boost, EBRT alone, and RP are all effective long-term therapeutic strategies, but patients require early counseling regarding potential treatments at the time of BCR, particularly in light of recent evidence supporting salvage RT initiation at low prostate-specific antigen values after RP. 35,36 We favor an open discussion with patients and selection between EBRT plus brachytherapy boost versus RP plus salvage RT (if needed) based on known differences in the side-effect profiles. [9][10][11] Although LDR brachytherapy boost was analyzed in the current analysis, many academic practices have adopted HDR brachytherapy as an alternative because of improved plan quality, less staff radiation exposure, and a hope for lower toxicity. 11,37 Indeed, Muralidhar et al. identified a prostate cancer-specific mortality improvement at 5 years for HRPC with the addition of a brachytherapy boost compared with EBRT alone. ...
Background
Patients with high‐risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost.
Methods
The authors compared quality‐adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external‐beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low‐dose‐rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479).
Results
Treatment strategies were compared using the incremental cost‐effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost‐effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost‐effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost.
Conclusions
EBRT with LDR brachytherapy boost may be a cost‐effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high‐value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost‐effective care, despite no change in overall survival.
... 40 Generally, the preservation of sexual function is better with LDR brachytherapy than with RP and is equivalent to that with EBRT. 41,42 In the JPOPS study by Okihara et al, 43 sexual function was preserved in 28.7% of patients at 3 years after LDR brachytherapy, while overall satisfaction significantly improved. Nakai et al evaluated erectile function and sexual QOL. ...
Around 40 years have passed since a modern low-dose-rate (LDR) brachytherapy for prostate cancer was introduced. LDR brachytherapy has become one of the definitive treatment options besides radical prostatectomy (RP) and external beam radiation therapy (EBRT). LDR brachytherapy has several advantages over EBRT such as a higher prescribed dose to the prostate gland while avoiding unnecessary irradiation of organs at risk, a precipitous dose gradient, a brief treatment time, and a short hospital stay. Previous reports revealed that the long-term oncologic outcomes of LDR brachytherapy are superior to those of EBRT. The oncologic outcomes of low- to intermediate-risk patients are equivalent to those of RP using the recurrence definition of surgery of prostate specific antigen (PSA) >0.2 ng/mL, while the oncologic outcomes of LDR brachytherapy as tri-modality (combined EBRT and androgen deprivation therapy) for high-risk patients is superior to that of RP using the recurrence definition of surgery. In respect of toxicity, urinary disorders such as urgency and frequency are often observed after the acute phase of treatment, but these events usually resolve, while the quality of life of urinary continence is well preserved for a long time. Erectile function decreases yearly, but is relatively preserved compared to RP. In conclusion, the most noteworthy strength of LDR brachytherapy for low- to intermediate-risk patients is the “brief treatment time” that provides long recurrence-free survival, while that for high-risk patients who received LDR brachytherapy (tri-modality) is “excellent disease control.”
... Par exemple, des études ont montré que les problèmes urinaires et sexuels causés par la curiethérapie à bas débit sont pires après l'ablation chirurgicale de la prostate. En effet, 91,8 % de récupération de la continence et 52,5% de récupération des aptitudes sexuelles sont obtenues avec la curiethérapie à bas débit contre 88,1% et 39,2% avec la prostatectomie radicale [38] [39]. Aussi, le risque de développement d'un cancer du côlon ou bien de la vessie suite à l'irradiation des cellules de la prostate est plus important en utilisant une radiothérapie externe qu'une radiothérapie interne. ...
Low dose rate brachytherapy is an internal radiotherapy technique for early prostate cancer. It consists of depositing radioactive seeds in the organ using needles inserted manually through the perineum under ultrasound imaging guidance. Despite the clinical success, this treatment is marked by many approximations inducing non-negligible side effects. Most of the robots developed for this intervention come up against the limits of medical robotics, namely size and acceptability that do not correspond to clinical constraints.In this thesis, we approached the problem differently by proposing a robot of 6-DOF parallel to minimize its size and collaborative to improve its acceptability by clinicians. After determining the kinematics, the optimal dimensions of the geometric parameters of the robot were obtained by optimization via a genetic algorithm. We proposed the design of the end-effector and the gravity compensation mechanism. To experimentally evaluate the compatibility of our solution with the requirements of the medical procedure, we adapted the 3D model to realize a prototype by 3D printing.Then, we developed an experimental bench that measures the placement of the needle in real time via a magnetic tracker, but also by calculation via kinematics. The prototype shows very interesting performance for the localized medical application and the average error between the measured and targeted position is 2.4 mm on the positioning plane and 0.78 mm along the axis of the insertion.
... Permanent seed brachytherapy (SEED-BT) has taken a place alongside external-beam radiotherapy (EBRT) and radical prostatectomy as one of the definitive therapeutic options for treating intermediate-risk prostate cancer. The most appealing reasons for selecting this treatment are favorable disease control rates and acceptable side effect profiles [1][2][3][4][5][6] . Prostate brachytherapy for patients with intermediate-risk disease has conventionally used a combination of SEED-BT and EBRT rather than SEED-BT alone 7 , especially if unfavorable factors such as a higher Gleason score and higher-volume disease are present. ...
We compared clinical outcomes associated with seed brachytherapy (SEED-BT) alone and SEED-BT plus external-beam radiotherapy (EBRT) for intermediate-risk prostate cancer using propensity score-matched analysis. From 2006 to 2011, 993 patients diagnosed with intermediate-risk were treated with either SEED-BT alone (n = 775) or SEED-BT plus EBRT (n = 158) at 3 tertiary hospitals. In the propensity score-matched analysis (102 pairs), median follow-up was 95 months (range 18–153 months). The 8-year biochemical recurrence-free rate (bRFR) was significantly better with SEED-BT alone than with combined radiotherapy (93.3% vs. 88.4%; HR 0.396; 95% CI 0.158–0.991). Grade 2 or greater late genitourinary toxicities were significantly fewer with SEED-BT alone than with combined radiotherapy (21.0% vs. 33.2%; HR 0.521; 95% CI 0.308–0.881). Similarly, grade 2 or greater late gastrointestinal toxicities were significantly fewer with SEED-BT alone (0% vs. 12.2%; HR 0.125; 95% CI 0.040–0.390). For the unfavorable intermediate-risk subgroups, SEED-BT alone yielded a significantly better bRFR than the combined radiotherapy (HR 0.325; 95% CI 0.115–0.915). SEED-BT alone might be a better disease-management plan than SEED-BT plus EBRT for intermediate-risk prostate cancer regardless of favorable and unfavorable characteristics.
Prostate cancer remains a prevalent concern worldwide, necessitating continual advancements in treatment modalities. This abstract explores the role of brachytherapy as a viable and effective option in the management of prostate cancer. Brachytherapy involves the implantation of radioactive sources directly into the prostate, providing a localized dose of radiation. n recent studies and clinical trials, brachytherapy has demonstrated promising outcomes, particularly in terms of disease control and patient outcomes. The treatment’s ability to deliver a concentrated intraprostatic dose, often in combination with external beam radiotherapy, has shown favorable results. Furthermore, brachytherapy’s impact on disease-free survival and its potential in reducing urinary and bowel toxicity have been subjects of investigation. This abstract delves into the technical aspects, patient outcomes, and emerging trends in brachytherapy for prostate cancer. By examining the current literature and research findings, we aim to shed light on the evolving role of brachytherapy in the comprehensive management of prostate cancer, emphasizing its potential as a valuable therapeutic option.
Background:
The health-related quality of life (HRQoL) of patients with localized prostate cancer (LPCa) after treatment mainly surgery and radiotherapy (RT) has received increasing attention. The aim of this study is to compare the HRQoL of LPCa after surgery and RT.
Methods:
Web of Science, Embase, PubMed and Cochrane databases were searched after January 2000 to observe the HRQoL scores after surgery and RT at different treatment time points.
Results:
A total of 28 studies were included in this study, and the results showed that LPCa received surgery had better bowel scores than RT at ≤3 (weighted mean differences [WMD] = 4.18; p = 0.03), 3-6 (WMD = 4.16; p < 0.001), 6-12 (WMD = 2.99; p = 0.004), 24-60 (WMD = 1.87; p = 0.06), and ≥60 (WMD = 4.54; p = 0.02) months. However, LPCa received RT had higher urinary scores at ≤3 (WMD = -7.39; p = 0.02), 3-6 (WMD = -6.03; p = 0.02), 6-12 (WMD = -4.90; p < 0.001), 24-60 (WMD = -3.96; p < 0.001), ≥60 (WMD = -2.95; p < 0.001) months and had better sexual scores at ≤3 (WMD = -13.58; p = 0.09), 3-6 (WMD = -12.32; p = 0.06), 6-12 (WMD = -12.03; p = 0.002), 24-60 (WMD = -11.29; p < 0.001), and ≥60 (WMD = -3.10; p = 0.46) months than surgery. The scores difference between surgery and RT decreased over time.
Conclusion:
Overall, for LPCa, surgery was associated with better HRQoL in the bowel domain, whereas RT was associated with better HRQoL in the urinary and sexual domains, with the difference between surgery and RT narrowing over time.
Aims:
To report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution.
Materials and methods:
In 2003-2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan-Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant.
Results:
Of 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3-7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival.
Conclusion:
In low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.
In this study, an improved Susceptible-Infected-Recovered (SIR) epidemic diffusion model for cholera is extended by including migration for susceptible people. This model is applied to a metapopulation that consists of two isolated cities where just susceptible individuals can migrate between the cities. The disease-free equilibrium, the endemic equilibrium points, and the basic reproductive number with unequal migration rates are analyzed for this metapopulation. Firstly, the study showed that the basic reproductive number depends on the migration rates between the cities. Then, showed that when the epidemic SIR system is stable, then the infected cases for cholera outbreak can reach zero in one city, but the infected cases in the other city still can stay positive. Finally, discussed three scenarios that depend on population sizes and migration rates of susceptible people between the cities and showed how important the migration rates are in the diffusion of the cholera outbreak by visualizing these three scenarios. Mathematics Subject Classification Primary: 92B05; Secondary: 92D40
Background
Oncological outcomes after localized prostate cancer (CaP) treatment are excellent and generally considered equivalent across treatment modalities. Thus, short, and long-term patient health related quality of life (HRQoL) is an important factor in treatment discussions. The purpose of this review was to assess the impact of treatment modality for localized CaP on HRQoL as reflected by recent published trials.
Methods
We conducted a literature review using the PubMed database for studies published between January 2010 and January 2021. We included randomized control trials and observational cohort studies examining HRQoL in patients with localized CaP treated with active surveillance, radical prostatectomy, external beam radiotherapy or brachytherapy.
Results
Four randomized control trials and 15 prospective cohort studies were reviewed. Current evidence suggests that surgery has the largest short and long-term negative effect on sexual function and incontinence but advantages with regards to bowel function and irritative-obstructive urinary symptoms. Radiation therapy mainly impacts urinary irritative symptoms and bowel bother. Short-term HRQoL outcomes for active surveillance are most favorable, however, during long-term follow up, there is no significant difference in comparison to radiation. Long-term global quality of life impact regarding anxiety, mental, emotional well-being, and fatigue seem to be equivalent between treatment modalities.
Conclusions
The choice of primary treatment modality for localized CaP results in a unique impact profile on cancer specific HRQoL in both the short and long-term periods. Understanding the different adverse events profiles can provide a basis for informing patients and clinicians regarding the impact of disease and treatments on quality of life and allow for a better patient centered discussion.
Context
Patients with prostate cancer and their physicians need knowledge of
treatment options and their potential complications, but limited data on complications
are available in unselected population-based cohorts of patients.Objective
To measure changes in urinary and sexual function in men who have undergone
radical prostatectomy for clinically localized prostate cancer.Design
The Prostate Cancer Outcomes Study, a population-based longitudinal
cohort study with up to 24 months of follow-up.Setting
Population-based cancer registries in 6 geographic regions of the United
States.Participants
A total of 1291 black, white, and Hispanic men aged 39 to 79 years who
were diagnosed as having primary prostate cancer between October 1, 1994,
and October 31, 1995, and who underwent radical prostatectomy within 6 months
of diagnosis for clinically localized disease.Main Outcome Measures
Distribution of and change in urinary and sexual function measures reported
by patients at baseline and 6, 12, and 24 months after diagnosis.Results
At 18 or more months following radical prostatectomy, 8.4% of men were
incontinent and 59.9% were impotent. Among men who were potent before surgery,
the proportion of men reporting impotence at 18 or more months after surgery
varied according to whether the procedure was nerve sparing (65.6% of non–nerve-sparing,
58.6% of unilateral, and 56.0% of bilateral nerve–sparing). At 18 or
more months after surgery, 41.9% reported that their sexual performance was
a moderate-to-large problem. Both sexual and urinary function varied by age
(39.0% of men aged <60 years vs 15.3%-21.7% of older men were potent at ≥18
months [P<.001]; 13.8% of men aged 75-79 years
vs 0.7%-3.6% of younger men experienced the highest level of incontinence
at ≥18 months [P = .03]), and sexual function
also varied by race (38.4% of black men reported firm erections at ≥18
months vs 25.9% of Hispanic and 21.3% of white men; P
= .001).Conclusions
Our study suggests that radical prostatectomy is associated with significant
erectile dysfunction and some decline in urinary function. These results may
be particularly helpful to community-based physicians and their patients with
prostate cancer who face difficult treatment decisions.
Prostate cancer is the most frequently diagnosed solid tumor in US men.
An estimated 179,300 men will be diagnosed as having the disease in 1999,1 and in more than 70% of these patients, the disease
will be clinically localized.2 Treatment options
for men with tumors confined to the prostate who have at least a 10-year life
expectancy include radical prostatectomy, external beam radiation, brachytherapy,
or expectant management. Each of these approaches is associated with a different
spectrum of morbidity and effects on quality of life, which may be short-term
or long-term.
To make informed choices about treatment alternatives, patients with
prostate cancer and their physicians need accurate information to assess the
potential and pattern of complications associated with each option. Numerous
investigators have assessed urinary and sexual function 1 or more years after
radical prostatectomy, with rates of incontinence ranging from 4% to 40% and
impotence from 29% to 75%.3- 12
These findings reflect the experiences of patients from selected clinical
practices,3- 5,7- 9,12
a health maintenance organization,10 and Medicare
recipients.6,11 Differences in
patient mix, study size, and data collection methods may explain the wide
range of results.
Limited data are available to describe the outcome experiences of unselected
population-based patients. We report results from the multicenter Prostate
Cancer Outcomes Study (PCOS), which has completed longitudinal assessments
of functional status in a large community-based cohort of patients with prostate
cancer treated with radical prostatectomy for clinically localized disease.
Purpose:
We reviewed the outcomes in men treated with permanent prostate brachytherapy (PPB).
Material and methods:
A total of 1,449 consecutive patients with a mean age of 68 years treated with PPB between 1992 and 2000 and mean pretreatment prostate specific antigen (PSA) 10.1 ng/ml were included in this study. Of the patients 55% presented with Gleason 6 tumors and 28% had Gleason 7 disease. A total of 400 patients (27%) were treated with neoadjuvant hormones and 301 (20%) were treated in combination with external radiation plus PPB. Several biochemical freedom from recurrence (BFR) definitions were determined. Statistical analysis consisted of log rank testing, Kaplan-Meier estimates and Cox regression analysis.
Results:
Median followup was 82 months with 39 patients at risk at for 144 months. Overall and disease specific survival at 12 years was 81% and 93%, respectively. The 12-year BFR was 81%, 78%, 74% and 77% according to the American Society for Therapeutic Radiology and Oncology (ASTRO), ASTRO-Kattan, ASTRO-Last Call and Houston definitions, respectively. The 12-year ASTRO-Kattan BFR using risk stratification was 89%, 78% and 63% in patients at low, intermediate and high risk, respectively (p = 0.0001). Multivariate analysis identified the dose that 90% of the target volume received (p <0.0001), pretreatment PSA (p = 0.001), Gleason score (p = 0.002), the percent positive core biopsies (p = 0.037), clinical stage (p = 0.689), the addition of hormones (p = 0.655) and the addition of external radiation (p = 0.724) for predicting BFR-ASTRO. Five-year disease specific survival was 44% in patients with a PSA doubling time of less than 12 months vs 88% in those with a PSA doubling time of 12 months or greater (p = 0.0001).
Conclusions:
PPB offers acceptable 12-year BFR in patients who present with clinically localized prostate cancer. Implant dosimetry continues as an important predictor for BFR, while the addition of adjuvant therapies such as hormones and external radiation are insignificant. In patients who experience biochemical failure it appears that PSA doubling time is an important predictor of survival.
Context.— Interstitial radiation (implant) therapy is used to treat clinically
localized adenocarcinoma of the prostate, but how it compares with other treatments
is not known.Objective.— To estimate control of prostate-specific antigen (PSA) after radical
prostatectomy (RP), external beam radiation (RT), or implant with or without
neoadjuvant androgen deprivation therapy in patients with clinically localized
prostate cancer.Design.— Retrospective cohort study of outcome data compared using Cox regression
multivariable analyses.Setting and Patients.— A total of 1872 men treated between January 1989 and October 1997 with
an RP (n=888) or implant with or without neoadjuvant androgen deprivation
therapy (n=218) at the Hospital of the University of Pennsylvania, Philadelphia,
or RT (n=766) at the Joint Center for Radiation Therapy, Boston, Mass, were
enrolled.Main Outcome Measure.— Actuarial freedom from PSA failure (defined as PSA outcome).Results.— The relative risk (RR) of PSA failure in low-risk patients (stage T1c,
T2a and PSA level ≤10 ng/mL and Gleason score ≤6) treated using RT,
implant plus androgen deprivation therapy, or implant therapy was 1.1 (95%
confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI,
0.3-3.6), respectively, compared with those patients treated with RP. The
RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason
score of 7 or PSA level >10 and ≤20 ng/mL) and high-risk patients (stage
T2c or PSA level >20 ng/mL or Gleason score ≥8) treated with implant compared
with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively.
The addition of androgen deprivation to implant therapy did not improve PSA
outcome in high-risk patients but resulted in a PSA outcome that was not statistically
different compared with the results obtained using RP or RT in intermediate-risk
patients. These results were unchanged when patients were stratified using
the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through
6 vs 7 vs 8 through 10.Conclusions.— Low-risk patients had estimates of 5-year PSA outcome after treatment
with RP, RT, or implant with or without neoadjuvant androgen deprivation that
were not statistically different, whereas intermediate- and high-risk patients
treated with RP or RT did better then those treated by implant. Prospective
randomized trials are needed to verify these findings.
Context
In men who develop an elevated serum prostate-specific
antigen level (PSA) after having undergone a radical prostatectomy, the
natural history of progression to distant metastases and death due to
prostate cancer is unknown.
Objective
To characterize the time course of disease progression
in men with biochemical recurrence after radical prostatectomy.
Design
A retrospective review of a large surgical series with
median (SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between
April 1982 and April 1997.
Setting An urban academic tertiary referral institution.Patients
A total of 1997 men undergoing radical
prostatectomy, by a single surgeon, for clinically localized prostate
cancer. None received neoadjuvant therapy, and none had received
adjuvant hormonal therapy prior to documented distant metastases.
Main Outcome Measures
After surgery, men were followed up with PSA
assays and digital rectal examinations every 3 months for the first
year, semiannually for the second year, and annually thereafter. A
detectable serum PSA level of at least 0.2 ng/mL was evidence of
biochemical recurrence. Distant metastases were diagnosed by
radionuclide bone scan, chest radiograph, or other body imaging, which
was performed at the time of biochemical recurrence and annually
thereafter.
Results
The actuarial metastasis-free survival for all 1997 men
was 82% (95% confidence interval, 76%-88%) at 15 years after
surgery. Of the 1997 men, 315 (15%) developed biochemical PSA level
elevation. Eleven of these underwent early hormone therapy after the
recurrence and are not included in the study. Of the remaining 304 men,
103 (34%) developed metastatic disease within the study period. The
median actuarial time to metastases was 8 years from the time of PSA
level elevation. In survival analysis, time to biochemical progression
(P<.001), Gleason score (P<.001), and PSA
doubling time (P<.001) were predictive of the probability
and time to the development of metastatic disease. An algorithm
combining these parameters was constructed to stratify men into risk
groups. Once men developed metastatic disease, the median actuarial
time to death was 5 years. The time interval from surgery to the
appearance of metastatic disease was predictive of time until death
(P<.02).
Conclusions
Several clinical parameters help predict the outcomes
of men with PSA elevation after radical prostatectomy. These data may
be useful in the design of clinical trials, the identification of men
for enrollment into experimental protocols, and counseling men
regarding the timing of administration of adjuvant
therapies.
Prostate brachytherapy has been practiced for nearly 100 years in various forms. However, technological advances over the past 20 years in imaging, computing, and devices have propelled this technique into the mainstream of prostate cancer treatments. A discussion of radiobiology principles is important to the understanding of modern brachytherapy technique. For low risk tumors, brachytherapy may be administered as monotherapy. For high risk tumors combination therapy with external beam therapy is indicated. Androgen ablation therapy is used for hormonal downsizing or for select high risk tumors. Diseases free survival appears similar to that seen with other definitive therapies for clinically localized prostate cancer. The short term morbidity of the procedure includes significant obstructive and irritative voiding symptoms. Future brachytherapy goals are discussed.
Objectives:
Health-related quality of life (HRQOL) is an increasingly important endpoint in prostate cancer care. However, pivotal issues that are not fully assessed in existing HRQOL instruments include irritative urinary symptoms, hormonal symptoms, and multi-item scores quantifying bother between urinary, sexual, bowel, and hormonal domains. We sought to develop a novel instrument to facilitate more comprehensive assessment of prostate cancer-related HRQOL.
Methods:
Instrument development was based on advice from an expert panel and prostate cancer patients, which led to expanding the 20-item University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) to the 50-item Expanded Prostate Index Composite (EPIC). Summary and subscale scores were derived by content and factor analyses. Reliability and validity were assessed by test-retest correlation, Cronbach's alpha coefficient, interscale correlation, and EPIC correlation with other validated instruments.
Results:
Test-retest reliability and internal consistency were high for EPIC urinary, bowel, sexual, and hormonal domain summary scores (each r >/=0.80 and Cronbach's alpha >/=0.82) and for most domain-specific subscales. Correlations between function and bother subscales within domains were high (r >0.60). Correlations between different primary domains were consistently lower, indicating that these domains assess distinct HRQOL components. EPIC domains had weak to modest correlations with the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12), indicating rationale for their concurrent use. Moderate agreement was observed between EPIC domains relevant to the Functional Assessment of Cancer Therapy Prostate module (FACT-P) and the American Urological Association Symptom Index (AUA-SI), providing criterion validity without excessive overlap.
Conclusions:
EPIC is a robust prostate cancer HRQOL instrument that complements prior instruments by measuring a broad spectrum of urinary, bowel, sexual, and hormonal symptoms, thereby providing a unique tool for comprehensive assessment of HRQOL issues important in contemporary prostate cancer management.
When more than one statistical test is performed in analysing the data from a clinical study, some statisticians and journal editors demand that a more stringent criterion be used for “statistical significance” than the conventional P<0.05.1 Many well meaning researchers, eager for methodological rigour, comply without fully grasping what is at stake. Recently, adjustments for multiple tests (or Bonferroni adjustments) have found their way into introductory texts on medical statistics, which has increased their apparent legitimacy. This paper advances the view, widely held by epidemiologists, that Bonferroni adjustments are, at best, unnecessary and, at worst, deleterious to sound statistical inference.
#### Summary points
Adjusting statistical significance for the number of tests that have been performed on study data—the Bonferroni method—creates more problems than it solves
The Bonferroni method is concerned with the general null hypothesis (that all null hypotheses are true simultaneously), which is rarely of interest or use to researchers
The main weakness is that the interpretation of a finding depends on the number of other tests performed
The likelihood of type II errors is also increased, so that truly important differences are deemed non-significant
Simply describing what tests of significance have been performed, and why, is generally the best way of dealing with multiple comparisons
Bonferroni adjustments are based on the following reasoning.1-3 If a null hypothesis is true (for instance, two treatment groups in a randomised trial do not differ in terms of cure rates), a significant difference (P<0.05) will be observed by chance once in 20 trials. This is the type I error, or α. When 20 independent tests are performed (for example, study groups are compared with regard to 20 unrelated variables) and the null hypothesis holds for all 20 comparisons, the chance of at least one test being significant is no longer 0.05, but 0.64. …
Purpose
We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen (PSA), or histologic progression as treatment indications for clinically localized prostate cancer.
Patients and Methods
This was a prospective, single-arm, cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data.
Results
A total of 450 patients have been observed with active surveillance. Median follow-up was 6.8 years (range, 1 to 13 years). Overall survival was 78.6%. The 10-year prostate cancer actuarial survival was 97.2%. Overall, 30% of patients have been reclassified as higher risk and have been offered definitive therapy. Of 117 patients treated radically, the PSA failure rate was 50%, which was 13% of the total cohort. PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years (P < .0001). The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years.
Conclusion
We observed a low rate of prostate cancer mortality. Among the patients who were reclassified as higher risk and who were treated, PSA failure was relatively common. Other-cause mortality accounted for almost all of the deaths. Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis.
Low-dose-rate prostate brachytherapy achieves a very high and effective intraprostatic dose. Implant quality parameters concentrate on the dose received by the prostate (D90, V100) but not that received by the periprostatic tissue. We calculated implant quality parameters, D90 and V100, for the magnetic resonance imaging (MRI)-defined prostate plus 2, 3, and 5 mm.
A total of 131 men with early-stage prostate cancer treated with iodine-125 brachytherapy represent all those treated with brachytherapy monotherapy in our institution in 2005. Postplan assessment was performed at 1 month using magnetic resonance (MR)-computed tomography (CT) fusion. The prostate V100 and D90 were calculated with 2-, 3-, and 5-mm margins. Results were compared with those in 8 patients with biopsy-proven local failure occurring in an experience of more than 1,100 implants.
Mean prostate V100 (SD) and D90 (SD) were 95.6% (4.1) and 117.2% (12.7). For prostate plus a 2-mm margin the D90 was 107.9% (14.3) and for a 3-mm margin 96.0 % (14.0). For prostate plus a 5-mm margin, the D90 was only 78.4% (11.0). The 8 patients experiencing local failure, despite adequate implants, had a lower mean V100 of 91.2% (SD, 2.8; p = 0.0008) and D90 of 103.7% (SD, 8.3; p = 0.002) and significantly inferior margin coverage.
Satisfactory coverage of a 2-mm and 3-mm periprostatic margin is obtained with the described planning approach. Coverage falls off significantly by 5 mm. The 8 patients who experienced local failure had significantly lower doses than the margin cohort. Although the V100 and D90 would be considered acceptable, the fall-off in margin coverage was observed by 3 mm.
To compare the oncological and functional outcomes reported after radical retropubic prostatectomy (RRP) versus brachytherapy (BT) in the treatment of low-risk prostatic cancer (CaP).
Between May 1999 and October 2002, 200 patients (mean age 65.3 +/- 8.7) were enrolled and randomized into two groups of 100 patients each to undergo RRP (group 1) or BT (group 2). Prior to and following treatment, all patients were evaluated by physical examination, PSA assay and compilation of IPSS, IIEF-5 and EORTC-QLQ-C30/PR25 questionnaires. Oncological results were reported at 5 years, while functional outcomes were reported at 6 months, and 1 and 5 years mean follow-up.
Of the 200 patients studied, 174 completed the 5-year follow-up assessment. With regards to oncological outcomes, similar 5-year biochemical disease-free survival rates were reported for RRP (91.0%) or BT (91.7%). At 6 months and 1 year, both techniques produced a significant decrease in quality of life aspects, while group 2 patients reported a significantly higher and longer lasting rate of urinary irritative disorders and better erective function than group 1. No differences in functional outcomes were encountered after 5 years in either group.
RRP and BT are two different options for the treatment of low-risk CaP, which produce different short-term sequelae in terms of urinary disorders and erective functions, but similar biochemical disease-free survival. Further studies with a higher number of patients and a longer follow-up are needed to evaluate their comparative effectiveness on overall disease-specific survival and metastatic disease.