Long-term Biochemical Control Research Articles

Previous radiotherapy negatively influences quality of life during 4 years of follow‐up in patients cured from acromegaly

Cross-sectional studies have shown impaired quality of life (QoL) in patients in biochemical control of acromegaly. The aim of this study was to assess longitudinal changes in QoL in a homogenous cohort of patients with sustained biochemical control of acromegaly. Prospective follow-up study. QoL was assessed using four health-related QoL questionnaires (HADS, Hospital Anxiety and Depression Scale; MFI-20, Multidimensional Fatigue Index; NHP, Nottingham Health Profile; and SF-36, Short Form-36) and one disease-specific acromegaly quality of life (ACRO-QOL) questionnaire in 82 patients (43 men) with strict biochemical control of acromegaly, aged 56 years (range 29-84 years) at baseline and after 4 years of follow-up. The mean duration of controlled disease was 12 years (range 1-26 years). During follow-up, scores in 5 of 26 QoL subscales significantly worsened: physical and social functioning (SF-36), physical fatigue (MFI-20), and psychological well-being and personal relations (ACRO-QOL). Using linear regression analysis, baseline item scores predicted the follow-up scores, indicating individual stability over time. Previous radiotherapy (n = 27, 33%) negatively influenced several QoL subscales at follow-up: energy, pain and social isolation (NHP), physical fatigue and reduction in activity and motivation (MFI-20), depression and total anxiety and depression scores (HADS) and physical performance (ACRO-QOL). During 4 years of follow-up in patients with long-term biochemical control of ACRO-QOL is subtly, but progressively impaired. Radiotherapy was the predominant indicator of progressive impairment in QoL.

Somatostatin analog treatment is associated with an increased sleep latency in patients with long-term biochemical remission of acromegaly

Background Somatostatin analogs induce alterations in sleep in healthy adults. Presently, it is unknown whether somatostatin analog treatment affects sleep parameters in patients with acromegaly. Design Case-control study. Patients and measurements We assessed sleepiness and sleep patterns in 62 adult patients (32 men, age 61 years (33–88 years) controlled by surgery alone or postoperative radiotherapy (69%), and/or somatostatin analogs (31%). We used two validated sleep questionnaires (Epworth sleepiness score and Münchener chronotype questionnaire). Patient outcomes were compared to controls. Results Sleep duration and timing of sleep were not different in patients compared to controls. However, sleepiness score was increased in all patients compared to controls: 6 (1–20) vs. 4 (0–14), P = 0.014 (median (range)), reflecting increased daytime sleepiness. Snoring was reported in 68% of both patients and controls ( P = 0.996), observed apnoea’s and restless legs in 23% and 37% of patients compared to 12% and 21% of controls ( P = 0.062 and P = 0.031, resp.). In addition, sleep latency was increased in patients treated by somatostatin analogs compared to patients cured by surgery and/ or radiotherapy (52 ± 48 min vs. 26 ± 40 min, P = 0.005), resulting in a delayed sleep onset (24:08 ± 1:26 h vs. 23:25 ± 0:43 h, P = 0.053). Sleep duration was unaffected. Conclusions Daytime sleepiness is increased in a homogeneous cohort of patients in long-term remission from acromegaly. In addition, somatostatin analog treatment increases sleep latency and delays sleep onset in patients with long-term biochemical control of growth hormone overproduction without altering total sleep duration.

Long-term results of biochemical control for intermediate- and high-risk prostate cancer treated with high-dose-rate brachytherapy and external beam radiotherapy without adjuvant androgen deprivation

Purpose: To report the long-term biochemical control rates (bC) according to the ASTRO Phoenix Consensus Conference, and prognostic factors of intermediate (IR) and high risk (HR) prostate cancer treated with external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR).

Alterations in body composition in acromegaly

Acromegaly is a condition characterized by growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion, and is associated with boney overgrowth, and soft tissue abnormalities due to anabolic, lipolytic, and sodium retaining actions of GH. GH and IGF-1 excess is associated with alterations in body composition, including an increase in body water and lean body mass, and a reduction in body fat. Achievement of biochemical control of the disease results in a reduction in body water and fat-free mass, and an increase in body fat. BMD is generally increased in acromegaly, though the anabolic effect of GH excess on bone is reduced, if not negated, by the presence of hypogonadism, particularly with regard to the trabecular compartment. Further studies are necessary to determine the effect of long-term biochemical control on bone density in subjects with acromegaly.

Pretreatment Nomogram Predicting Ten-Year Biochemical Outcome of Three-Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy for Prostate Cancer

To update our previously published nomogram predicting for biochemical outcome with 10-year data from a larger cohort of patients treated with three-dimensional conformal radiotherapy (RT) or intensity-modulated RT for localized prostate cancer. From 1988 to 2004, 2253 patients were treated with three-dimensional conformal RT or intensity-modulated RT for clinical Stage T1-T3 prostate cancer. Prescription doses ranged from 64.8 to 86.4 Gy. The median follow-up time was 7 years. The nomogram was developed using a proportional hazards regression model predicting for the probability of biochemical relapse after RT according to the nadir plus 2 ng/mL definition of prostate-specific antigen (PSA) relapse. The 10-year PSA relapse-free survival rate was 62%. The nomogram incorporated the following variables to predict likelihood of PSA failure after RT: pretreatment PSA level, Gleason score, radiation dose, use of neoadjuvant androgen deprivation, and clinical stage. The concordance index of this long-term nomogram was 0.72. A nomogram predicting the 10-year probability of biochemical control after three-dimensional conformal RT or intensity-modulated RT for prostate cancer was reasonably accurate and discriminating. The nomogram also provided evidence that long-term biochemical control can be achieved after conformal RT for the treatment of localized prostate cancer.

Long-Term Prostate Cancer Control Using Palladium-103 Brachytherapy and External Beam Radiotherapy in Patients with a High Likelihood of Extracapsular Cancer Extension

To report the long-term biochemical control rates with brachytherapy-based treatment for patients with prostate cancer at high risk of extracapsular cancer extension. A total of 243 consecutive patients with at least one higher risk factor (Gleason score of 7 or worse, prostate-specific antigen [PSA] level greater than 10 ng/mL, or elevated prostatic acid phosphatase level greater than 2.5 U) who were treated with palladium-103 plus supplemental external beam radiotherapy from 1992 through 1996 were included in this study. Patients received 41 Gy external beam radiotherapy to a limited pelvic field, followed 4 weeks later by a palladium-103 boost. The prescribed minimal palladium-103 dose to the prostate was 80 to 90 Gy. Freedom from biochemical failure was defined as a serum PSA level of 0.2 ng/mL or less at the last follow-up visit. Of the 243 patients, 41 developed biochemical failure. The overall actuarial freedom from biochemical progression rate at 13 years was 81%, with 198 patients followed up for longer than 5 years. The overall actuarial freedom from failure rate for the 93 patients with a PSA level of 10 ng/mL or greater and Gleason score of 7 or greater was 74% at 5 years and 72% at 10 years. The overall actuarial freedom from failure rate for the 66 patients with elevated prostatic acid phosphatase was 65% at 10 years. The absolute risk of failure decreased progressively with time, falling to 1% by 6 years after treatment. On Cox proportional hazard multivariate analysis, considering each factor as a continuous variable, the strongest predictor of failure was the acid phosphatase level (P <0.0001), followed by Gleason score (P = 0.42) and PSA level (P = 0.15). The evidence from this patient group at high risk of extracapsular cancer extension suggests that the relatively high tumor control rates with brachytherapy-based therapy are durable.

Prostate-Specific Antigen Kinetics After Brachytherapy or External Beam Radiotherapy and Neoadjuvant Hormonal Therapy

Objectives To characterize the kinetics of prostate-specific antigen (PSA) after radiotherapy (RT) and neoadjuvant hormonal therapy (NHT) for localized prostate cancer. Methods The PSA kinetics of 75 consecutive patients who had undergone RT and NHT (median time 4 months) were followed up for a minimum of 24 months after treatment. RT included a permanent iodine-125 implant (n = 29), a temporary iridium-192 implant as a boost to external beam RT (n = 21), and sole external beam RT (n = 25). A median number of 11 PSA levels per patient were analyzed. Results After a first nadir (median level 0.1 ng/mL 3 months after RT), rising PSA levels were found in 83% of patients and progressively rising PSA levels until the end of follow-up or salvage hormonal therapy for 21% of patients. The PSA levels dropped again after one (23%), two (21%), or more (17%) consecutive increases up to a median level of 0.6 ng/mL (median time 16 months after RT), so that a nadir of 0.1 ng/mL was reached for a second time (median time 35 months after RT). A first nadir of less than 0.1 ng/mL, a PSA increase of less than 1 ng/mL, and a longer PSA doubling time (median time 10 months) were strongly predictive for long-term biochemical control. Conclusions Temporarily rising PSA levels can be expected for most patients after primary RT and NHT following a first nadir. The increasing effects of testosterone owing to NHT withdrawal have a stronger effect than RT in the first months after treatment.

25-Year Prostate Cancer Control and Survival Outcomes: A 40-Year Radical Prostatectomy Single Institution Series

We report on 25-year cancer control and survival outcomes after radical prostatectomy in a single center series of patients treated during a 40-year period. Between 1954 and 1994, 787 consecutive patients underwent radical prostatectomy at Virginia Mason Medical Center in Seattle, Washington. Kaplan-Meier 25-year probabilities of prostate cancer specific, overall, prostate specific antigen progression-free, local and distant progression-free survival were determined. Multivariate Cox regression models addressed prostate cancer specific mortality. Prostate cancer specific survival, overall survival, prostate specific antigen progression-free survival, local and distant progression-free survival ranged from 99.0% to 81.5%, 93.5% to 19.3%, 84.8% to 54.5%, 95.3% to 87.8% and 95.9% to 78.2%, respectively. In univariate analyses pathological stage, surgical margin status, pathological Gleason sum, delivery of hormonal therapy and radiotherapy represented statistically significant predictors of prostate cancer specific mortality (all p < or =0.001). In multivariate analyses only Gleason sum (p = 0.03) and delivery of hormonal therapy (p < 0.001) remained significant. This is one of the most mature radical prostatectomy series. It demonstrates that long-term biochemical cancer control outcomes after radical prostatectomy might be suboptimal. However, local and distant control outcomes are excellent, and cancer specific mortality is minimal even 25 years after surgery.

Biologically Effective Dose Values for Prostate Brachytherapy: Effects on PSA Failure and Post-Treatment Biopsy Results

Purpose/Objective: The ability to perform dose response analyses for brachytherapy with different isotopes and combined with EBRT has been difficult due to differences in doses rates, half lives and fractionation. To address this problem, we derived biologically effective dose (BED) equations for different isotopes and treatments and tested their effects on PSA failure and post-treatment biopsy. Materials/Methods: 1377 patients were treated with brachytherapy from 1990 to 2003. Disease factors were as follows: PSA ≤10 in 70%, >10–20 in 20% and >20 in 10%; Gleason score 2–6 in 69%, 7 in 20.5% and 8–10 in 10.5%; clinical stage ≤ t2a in 65% and ≥ t2b in 35%. There were three treatment groups: brachytherapy alone (571 patients) with either I–125 or Pd–103, hormonal therapy and brachytherapy (371 patients) and trimodality therapy (hormonal therapy (9 months), implant and EBRT)(435 patients). Implant dose (D90) was derived from the one month post-implant CT based dosimetry. The linear–quadratic model was used to determine the BED for EBRT using the equation BED = nd 1 + (d/α/β) where n=number of fractions, d=dose per fraction, α/β = 2. The equation for the isotopes was BED = (R0/λ)1+R0/(μ+ λ)(α/β) where R0 = initial dose rate of implant = (D90)(λ), λ=radioactive decay constant = 0.693/T1/2, T1/2 =radioactive half–life of isotope, μ=repair rate constant = 0.693/t1/2, t1/2=tissue repair half-time. BEDs from implant and EBRT were added for combined therapy. Patients were divided into 7 BED dose groups. The groups were ≤ 100 (45 patients), >100–120 (32 patients), >120–140 (51 patients), >140–160 (97 patients), >160–180 (191 patients), >180–200 (311 patients) and > 200 (594). Follow-up ranged from 2–14 years (median−4.2). PSA failure was defined by the ASTRO definition. Biopsy outcome was determined by the last biopsy result 2 or > years post-treatment. Results: The overall freedom from PSA failure (FFPF) at 10 years was 87%. BED groupings significantly affected PSA failure with demonstrated improvement in FFPF rates with increasing BED. The 10 year FFPF for the BED groups ≤100, >100–120, >120–140, >140–160, >160–180, >180–200 and >200 were 46%, 68%, 81%, 85.5%, 90%, 90% and 92%, respectively (<0.0001). Based on the above findings, patients were divided into two BED dose groups < 150 (169 patients) and ≥150 (1152 patients). 10 year FFPF rates were 69% and 91% for the two groups, respectively (p<0.0001). Cox regression found that BED and Gleason Score had the greatest effect with p values of p<0.0001. The overall last positive biopsy rate was 7% (31/446). Lower positive biopsy results were associated with increasing BED dose groups. The positive biopsy results for BED group ≤100, >100–120, >120–140, >140–160, >160–180, >180–200 and >200 were 24% (8/33), 15% (3/20), 6% (2/33), 6% (3/52), 7% (6/82), 1% (1/72), 3% (4/131), respectively (<0.0001). Dividing patients into two BED dose groups (< 150, ≥ 150) revealed positive biopsy rates of 13% (14/110) and 4%(13/312), respectively, p <0.0001. Logistic regression analysis revealed BED to be the most significant predictor of biopsy results (p=0.006). Conclusions: BED equations allow the comparison of different isotopes and combined therapies in the brachytherapy management of prostate cancer. The effects of BED on FFPF and post-treatment biopsy reveal a strong dose response relationship. These results support the recommended brachytherapy dose prescriptions but emphasize the need to achieve the stated dose goals. If current prescription doses can be achieved, excellent long-term biochemical and local control rates can be realized.

Long-term Prostate Cancer Control (13 Year Actuarial) in Patients with a High Likelihood of Extracapsular Cancer Extension Using PD-103 Brachytherapy and Supplemental Beam Radiation

Purpose/Objective: To summarize long-term biochemical control rates with brachytherapy-based treatment for prostate cancer at high risk of having extracapsular cancer extension (ECE). Patients diagnosed with high risk prostate cancer are often discouraged from undergoing brachytherapy because of the lack of long-term follow-up data. Accordingly, we have updated our ongoing analysis of higher risk patients using strict biochemical criteria to determine patients cancer-free status.

Role of Medical Therapy in the Management of Acromegaly

Medical therapy plays an important role in the management of patients with acromegaly and is commonly used adjunctively after surgical resection of the pituitary tumor. Generally, surgery alone provides a 50 to 70% rate of cure; however, the outcome depends on the experience and ability of the surgeon and the characteristics of the tumor. The role of postsurgical medical therapy is to achieve long-term biochemical control of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. In some patients, medical therapies may be implemented sooner as primary or preoperative therapy. Somatostatin analogs have been the mainstay of medical therapy for acromegaly. The somatostatin analog octreotide produces normalization of IGF-I in approximately 50% of patients but is associated with gastrointestinal adverse effects, including the development of gallstones. Octreotide requires thrice-daily subcutaneous administration. Long-acting formulations of somatostatin analogs (octreotide LAR, lanreotide) are at least as effective and as well tolerated as short-acting octreotide. Unfortunately, some patients are suboptimally responsive to or become intolerant of these agents. Pegvisomant belongs to a new class of agents known as GH-receptor antagonists. This novel agent competitively binds to the GH receptor, blocking IGF-I production. Pegvisomant is highly effective in achieving normal IGF-I concentrations and in reducing signs and symptoms of acromegaly, even in patients resistant to previous treatments. Pegvisomant has been proved safe and well tolerated and has no effect on gallbladder motility. GH levels remain elevated. Transient elevations in liver enzyme levels require monitoring but rarely necessitate termination of therapy. Normalizing IGF-I concentrations with pegvisomant also may have a beneficial effect on carbohydrate metabolism and cardiovascular risk.

Rising prostate-specific antigen after primary prostate cancer therapy

An estimated 20-40% of men experience a biochemical recurrence within 10 years of definitive prostate cancer treatment. No single prostate-specific antigen (PSA) value is invariably associated with clinical metastasis or cancer-specific survival; PSA kinetics might prove to be a more important predictor of eventual progression-free survival and cancer-specific survival than absolute PSA level alone. With only one-third of patients progressing from biochemical recurrence to clinical disease, therapeutic morbidity should not outpace risk of disease progression. Salvage radiation therapy following radical prostatectomy has widely variable long-term biochemical control rates (from 18 to 64% depending on the follow-up period). Early hormonal therapy delivered as castration or complete androgen blockade might delay clinical metastasis in patients with high-risk pathologic disease; however, the adverse effects and morbidity of long-term therapy must not be underestimated. Non-steroidal antiandrogens as monotherapy for early biochemical recurrence, particularly for younger men who wish to preserve their libido and sexual potency, have received considerable attention, but there are conflicting data on long-term outcomes. Because of their favorable adverse-effect profiles, non-traditional therapies that exert localized hormonal or cellular effects are receiving considerable attention for treatment of early, PSA-only recurrence. Data from animal models provide a rationale for the use of these therapies, but there is a lack of evidence to support prolongation of progression-free survival or cancer-specific survival.

IMPACT OF SURGICAL DELAY ON LONG-TERM CANCER CONTROL FOR CLINICALLY LOCALIZED PROSTATE CANCER

Radical retropubic prostatectomy (RRP) as definitive management for clinically localized prostate cancer is commonly performed within months of diagnosis. Despite patient anxiety there is little evidence to suggest that a delay of several months from diagnosis to RRP is associated with a worse cancer control rate. However, a recent study cast doubt on the safety of such a delay with respect to cancer control. Therefore, in a contemporary series we determined long-term cancer control in men who underwent RRP for clinically localized prostate cancer with some treated early and others treated after a longer delay. We analyzed data on 926 men who underwent RRP between January 1989 and December 1994. Age, preoperative serum prostate specific antigen (PSA), biopsy Gleason score, clinical and pathological stage, and biochemical recurrence were compared between 162 men who underwent RRP 60 days or less from biopsy and 764 who underwent RRP after a greater delay. Disease-free (PSA less than 0.2 ng/ml) survival rates were compared using Kaplan-Meier analysis. Pathological staging was compared using logistic regression. The different groups were well matched for age, serum PSA, pathological stage and followup. However, significantly more men who underwent RRP between 121 and 150 days, and 151 days or greater had T1c disease (48% and 57% vs 35%, p<0.04 and <0.0001, respectively). In addition, significantly more men operated on at 151 days or greater had biopsy Gleason scores 2 to 6 (86% vs 65%, p<0.0001) and significantly fewer had Gleason score 7 disease (13% vs 30%, p<0.002). Men who underwent RRP after 60 or less days had 5 and 10-year biochemical disease-free survival rates comparable to those in men who underwent RRP after 61 to 90, 91 to 120 and 121 to 150 days after diagnosis (82% and 78%, 86% and 78%, 86% and 75%, and 86% and 82%, respectively). Those operated on at 151 days or greater had significantly greater 5 and 10-year biochemical disease-free survival rates (89% and 87%, p<0.04). However, when patients were stratified into different subgroups based on clinical stage, serum PSA and biopsy Gleason score a delay of 150 days or greater no longer impacted differently on long-term cancer control rates. Delays of up to several months from prostate cancer diagnosis to RRP do not appear to impact long-term biochemical cancer control rates. Therefore, patients can be reassured that there is no immediate urgency to perform RRP after prostate cancer diagnosis, especially in those with T1c disease and biopsy Gleason scores less than 7.

Clinical results of combined treatment conformal high-dose-rate iridium-192 brachytherapy and external beam radiotherapy using staging lymphadenectomy for localized prostate cancer

Purpose To report the first long-term biochemical control rate of patients treated with two protocols using a combination of external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy for localized prostate cancer in Japan. Methods and materials Between October 1997 and July 2001, 71 patients with localized prostatic adenocarcinoma were treated with a combination of EBRT and HDR brachytherapy. Patient age ranged from 58 to 81 years (mean 70.5). Of the 71 patients, 12, 41, and 18 had Stage T1c, T2, and T3, respectively, according to the International Union Against Cancer classification system (1997). The mean initial prostate-specific antigen (PSA) level was 24.2 ng/mL (median, 11.9 ng/mL); 30% of the patients had an initial PSA level >20 ng/mL. Of the 71 patients, 31 had received neoadjuvant hormonal therapy. Hormonal therapy before treatment was stopped at the beginning of RT in all cases. Patients in this series were treated on two protocols. In the initial protocol, patients were treated with whole pelvis EBRT to 45.0 Gy in 25 fractions and three HDR fractions of 5.5 Gy each (35 patients). In the second protocol, patients were treated with prostatic EBRT to 41.8 Gy in 19 fractions, with an added staging lymphadenectomy to rule out lymph node metastasis for patients with high-risk factors, and four HDR fractions of 5.5 Gy each (36 patients). The American Society for Therapeutic Radiology and Oncology consensus definition for biochemical failure was used. Acute and chronic toxicities were scored using the Radiation Therapy Oncology Group guidelines. Follow-up ranged from 24 to 65 months (median, 44 months). Results Of the 71 patients, 69 were alive at the last follow-up. Two patients had died of hepatocellular carcinoma and gastric cancer at 3.5 and 4.0 years after treatment with no biochemical failure. Sixty-six patients (93%), including the two who had died of intercurrent disease, showed a tendency for a PSA decline after treatment and had no biochemical or clinical evidence of disease at the last follow-up visit. Sixty patients (85%) achieved PSA nadir levels of ≤1.0 ng/mL. The biochemical/clinical failure-free control rate at 3 and at 5 years was 93% and 93%, respectively. The bladder and rectal complications were minimal. Conclusion Despite the high frequency of high-risk patients in the present patient population, the actuarial biochemical control rate was 93% at 5 years. Acute and chronic toxicity with this method was acceptable. Additional long-term follow-up is required to assess this treatment, because the median survival is not likely to be reached for several years.

Salvage radiotherapy in the treatment of prostate cancer

For patients undergoing radical prostatectomy for prostate adenocarcinoma, the most common cause of failure is an asymptomatic increase in levels of prostate-specific antigen (PSA). Salvage radiotherapy (RT) to the prostate bed has been used when there is no clinical evidence of metastatic disease. However, this is still not widely accepted because there is currently no consensus on the optimal management of an isolated PSA failure. Salvage RT given in a select group of patients is effective, with a 70% to 80% biochemical response rate and a long-term biochemical control rate as high as 35% to 40%. These data indicate that RT offers a substantial risk of curative salvage of patients who fail radical prostatectomy. Although there is interest in studying investigational modalities (eg, vaccine therapy) among patients with asymptomatic, PSA-detected recurrences after surgery, caution must be applied, and treatment modalities with known curative potential (ie, RT) should be used before noncurative techniques are attempted. This article outlines the rationale, results, and toxicity of salvage RT for an asymptomatic increase in PSA levels, with emphasis on identifying patients with favorable prognostic factors with higher rates of long-term biochemical control with local treatment.

Long-term results of three-dimensional conformal adjuvant and salvage radiotherapy after radical prostatectomy

Objectives To evaluate the efficacy and toxicity of three-dimensional conformal radiotherapy (3D-CRT) in the adjuvant and salvage setting after radical prostatectomy (RP). Methods From 1986 to 1997, 38 patients received adjuvant 3D-CRT, with a median time from RP to 3D-CRT of 2.8 months, and 57 patients were treated with salvage RT for a rising prostate-specific antigen with a median time to 3D-CRT of 27.7 months. The median radiation dose was 64.8 Gy. The median follow-up from completion of RT was 7.0 years (range 1.0 to 14.2). Results Overall, the 8-year actuarial rate of biochemical disease-free survival was 40% in all patients. The 8-year biochemical disease-free survival rate was 45% (standard error [SE] 8%) and 30% (SE 7%) for the adjuvant and salvage group, respectively, from RT completion. When measured from the date of RP, the 5 and 8-year biochemical disease-free survival rate for salvage radiotherapy was 58% and 37%, respectively. The corresponding results for adjuvant RT were similar at 53% and 45%. On multivariate analysis, the Gleason score was the only prognostic factor predictive of prostate-specific antigen failure in the salvage group. No prognostic factor was significant in the adjuvant group. The prevalence of major complications after 3D-CRT was low using physician-reported data. Conclusions Long-term biochemical control can be achieved in both adjuvant and salvage settings. For patients receiving salvage RT, a Gleason score greater than 7 was predictive of prostate-specific antigen failure. Prospective trials are needed to improve further on these results.

Does short-term androgen deprivation substitute for radiation dose in the treatment of high risk prostate cancer

Does short-term androgen deprivation substitute for radiation dose in the treatment of high risk prostate cancer

The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer

Purpose : Some prostate cancers may have molecular alterations that render them less responsive to radiation therapy; identification of these alterations before treatment might allow improved treatment optimization. This study investigated whether p53, a potential molecular determinant, could predict long-term radiation therapy outcome in a restricted group of relatively favorable-risk prostate cancer patients treated uniformly with irradiation alone. Methods and Materials : This study included 53 patients previously treated with radiotherapy for favorable-to-intermediate-risk prostate cancer. These patients were selected for relatively low pretreatment PSAs (≤21 ng/mL) and Gleason scores (≤7) to decrease the likelihood of nonlocalized disease, because disease localization was necessary to examine the efficacy of localized radiation therapy. The status of p53 was immunohistochemically assessed in paraffin-embedded pretreatment biopsy specimens, along with appropriate controls. This marker was selected based upon a usable mutation prevalence in early-stage prostate cancer and its potential linkage with radiation response via cell cycle, DNA repair, and cell death pathways. Correlation between p53 mutation and clinical outcome was analyzed in univariate and multivariate fashion and included conventional prognosticators, such as stage, grade, and PSA. Freedom from biochemical failure was determined using American Society for Therapeutic Radiology and Oncology criteria. Limitations of prior studies were potentially avoided by requiring adequate posttreatment follow-up (median follow-up in nonfailing patients of 5.1 years), as well as pretreatment PSA and Gleason scores that suggested localized disease, and uniformity of treatment. Results : The total group of 53 favorable-to-intermediate-risk patients demonstrated an actuarial biochemical failure rate of 35% at 5 years. Forty percent of all specimens had a greater than 10% labeling index for p53 mutation, and actuarial biochemical control was found to strongly and independently correlate with p53 status. Patients with higher p53 labeling indices demonstrated significantly higher PSA failure rates ( p < 0.001). In contrast, p53 status did not correlate with pretreatment PSA, grade, or tumor stage. Similarly, pretreatment PSA (log-rank 0.22), Gleason score (log-rank 0.93), and T stage (log-rank 0.15) were not prognostic for outcome in this group of patients selected for their relatively favorable clinical characteristics. Conclusions : ( 1) p53 status in pretreatment biopsies strongly predicted for long-term biochemical control after radiation therapy in favorable-to-intermediate-risk prostate cancer patients. ( 2) If validated in other independent clinical data sets, p53 status should be considered as a stratification factor in future clinical trials and could be useful in guiding treatment. Abnormal p53 status might favor surgical management, aggressive dose escalation, or p53-targeted therapy.

The Role of p53 in radiation therapy outcomes for prostate cancer -- early stage disease

The Role of p53 in radiation therapy outcomes for prostate cancer -- early stage disease

What is the optimal dose for I-125 prostate implants? A dose response analysis of long-term urinary symptoms, biochemical control and post-treatment biopsy

What is the optimal dose for I-125 prostate implants? A dose response analysis of long-term urinary symptoms, biochemical control and post-treatment biopsy