Prostate cancer‐specific mortality and the extent of therapy in healthy elderly men with high‐risk prostate cancer

BACKGROUND:

The risk of prostate cancer‐specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external‐beam radiation to the prostate and seminal vesicles, and androgen‐suppression therapy (CMT) in this population.

METHODS:

The study cohort comprised 764 men aged ≥65 years with high‐risk prostate cancer (T3 or T4N0M0, prostate‐specific antigen >20 ng/mL, and/or Gleason score 8‐10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM.

RESULTS:

The median patient age was 73 years (interquartile range, 70‐77 years). After a median follow‐up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12‐0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017).

CONCLUSIONS:

Elderly men who had high‐risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high‐risk prostate cancer. Cancer 2010. © 2010 American Cancer Society.     

Prostate-specific antigen kinetics following external-beam radiotherapy and temporary (Ir-192) or permanent (I-125) brachytherapy for prostate cancer

Background and purpose

The aim of the study was the evaluation of PSA kinetics after different radiotherapy methods.

Materials and methods

Two-hundred and ninety five patients received external-beam radiotherapy (EBRT; 70.2 Gy; n = 135), Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18 Gy + 50.4 Gy; n = 66) or I-125 brachytherapy (LDR-BT; 145 Gy; n = 94) as monotherapy. “PSA bounce” was defined as a PSA rise of ?0.2 ng/ml followed by spontaneous return to prebounce level or lower, biochemical failure as “nadir + 2 ng/ml”.

Results

Patients without biochemical failure reached a lower nadir after brachytherapy (median ?0.05 ng/ml after LDR- and HDR-BT without NHT) in comparison to EBRT (0.55 ng/ml without NHT; p < 0.01). Not a single patient without NHT and a nadir <0.1 ng/ml failed biochemically (0% vs. 45% with a nadir ?0.1 ng/ml; p < 0.01). PSA bounces were found predominantly in the LDR-BT group (42% vs. 23%/20% after HDR-BT/EBRT; p < 0.01). In a multivariate Cox regression analysis, LDR-BT and HDR-BT were associated with a significantly lower biochemical failure rate in comparison to EBRT.

Conclusions

PSA kinetics differ significantly following different radiotherapy methods. A lower nadir and a higher biochemical control rate suggest a higher radiobiological efficiency of brachytherapy in comparison to EBRT (with a dose of 70.2 Gy).     

Impact of the percentage of positive prostate cores on prostate cancer-specific mortality for patients with low or favorable intermediate-risk disease.

PURPOSE: We investigated whether pretreatment factors predicted time to prostate cancer-specific mortality (PCSM) after conventional-dose and conformal radiation therapy (CRT). PATIENTS AND METHODS: Between 1988 and 2002, 421 patients with low (prostate-specific antigen [PSA] level < or = 10 ng/mL and biopsy Gleason score < or = 6) or favorable intermediate-risk (PSA > 10 to 15 ng/mL or biopsy Gleason score 3 + 4, but not both factors) disease underwent CRT (median dose, 70.4 Gy). Cox regression multivariable analysis was performed to determine whether the PSA level, Gleason score, T category, or the percentage of positive cores (% PC) predicted time to PCSM after CRT. After a median follow-up of 4.5 years, 117 (28%) patients have died. RESULTS: The % PC was the only significant predictor (Cox P < or =.03). The relative risk of PCSM after CRT for patients with > or = 50% as compared with less than 50% PC was 10.4 (95% CI, 1.2 to 87; Cox P =.03), 6.1 (95% CI, 1.3 to 28.6; Cox P =.02), and 12.5 (95% CI, 1.5 to 107; Cox P =.02) in men with a PSA < or = 10 and Gleason score < or = 6, PSA < or = 10 and Gleason score < or = 7, and PSA < or = 15 and Gleason score < or = 6, respectively. By 5 years after CRT, 5% to 9% compared with less than 1% (log-rank P < or =.01) of these patients experienced PCSM if they had > or = 50% compared with less than 50% PC, respectively. CONCLUSION: CRT dose-escalation techniques, the addition of hormonal therapy, or both should be considered in the management of patients with low or favorable intermediate-risk disease and > or = 50% PC.     

Cancer-specific mortality after radiation therapy with short-course hormonal therapy or radical prostatectomy in men with localized, intermediate-risk to high-risk prostate cancer

BACKGROUND: The presence of multiple determinants of aggressive cancer biology may impact prostate cancer-specific mortality (PCSM) rates compared with fewer factors. The authors estimated PCSM after radiation therapy with short-course androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with clinically localized, intermediate-risk to high-risk prostate cancer. METHODS: The study cohort included 3240 men treated from 1981 to 2002 with RT with 6 months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason score 7-10, or clinical tumor category T2b or T2c). Competing risks regression analyses were used to determine whether the number of risk factors present was associated with time to PCSM. RESULTS: Men with all 3 risk factors had significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of 9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1 or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95% CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of intermediate-risk to high-risk prostate cancer have significantly increased estimates of PCSM despite aggressive therapy compared with men with only 1 or 2 determinants. These men are appropriate candidates for enrollment onto randomized controlled trials evaluating the benefit of adding systemic therapies such as docetaxel to RT+AST or RP.     

Young age under 60 years is not a contraindication to treatment with definitive dose escalated radiotherapy for prostate cancer

Background

It is widely believed that younger prostate cancer patients are at greater risk of recurrence following radiotherapy (RT).

Methods

From 1992 to 2007, 2168 (395 age ?60) men received conformal RT alone for prostate cancer at our institution (median dose = 76 Gy, range: 72-80). Multivariable analysis (MVA) was used to identify significant predictors for BF and PCSM. Cumulative incidence was estimated using the competing risk method (Fine and Gray) for BF (Phoenix definition) and PCSM to account for the competing risk of death.

Results

With a median follow-up of 72.2 months (range: 24.0-205.1), 8-year BF was 27.1% for age ?60 vs. 23.7% for age >60 (p = 0.29). Eight-year PCSM was 3.0% for age ?60 vs. 2.0% for age >60 (p = 0.52). MVA for BF identified initial PSA [adjusted HR = 1.7 (PSA 10-20), 2.6 (PSA >20), p < 0.01], Gleason score [adjusted HR = 2.1 (G7), 1.9 (G8-10), p < 0.01], T-stage [adjusted HR = 1.7 (T2b-c), 2.6 (T3-4), p < 0.01], and initial androgen deprivation therapy (ADT) [adjusted HR = 0.38 (ADT >12 months), p < 0.01] as significant, but not age or ADT <12 months. MVA for PCSM identified Gleason score [adjusted HR = 3.0 (G8-10), p = 0.01] and T-stage [adjusted HR = 8.7 (T3-4), p < 0.01] as significant, but not age, PSA, or ADT.

Conclusion

This is the largest, most mature study of younger men treated with RT for prostate cancer that confirms young age is not prognostic for BF.     

Outcomes from Gleason 7, intermediate risk, localized prostate cancer treated with Iodine-125 monotherapy over 10 years

Background and purpose

The effect of predominating Gleason grade (3 + 4 versus 4 + 3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA ? 10 ng/ml, localised PCa is reported.

Materials and methods

Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA ? 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS).

Results

Median follow-up was 5.0 years (range 2.0-10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3 + 4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4 + 3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D₉₀ ? 140 Gy (50% total), compared with 77.0% below 140 Gy (p = 0.08).

Conclusions

Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy.     

Association of early PSA failure time with increased distant metastasis and decreased survival in prostate brachytherapy patients

Background and purpose

We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality.

Materials and methods

We retrospectively analyzed 2818 patients who underwent brachytherapy ± external beam radiation therapy (EBRT) ± androgen deprivation therapy (ADT). With median follow-up of 5.52 years, 264 patients experienced PSA failure at a median time of 3.25 years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5 years, 3 years, or 5 years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS).

Results

Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3 years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34–6.55; p = 0.000); HR for PCSM was 2.79 (95% CI: 1.45–5.38; p = 0.002); and HR for overall mortality was 2.28 (95% CI: 1.50–3.48; p = 0.000).

Conclusion

Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality.     

Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer

BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS.: A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS.: Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.     

Three-dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture

BACKGROUND:

Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown.

METHODS:

From the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992‐2004 were identified. By using Kaplan‐Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall‐related fracture outside the radiation field.

RESULTS:

After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38‐2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56‐1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88‐3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17‐1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97‐2.10). The number needed to treat to result in 1 hip fracture during a 10‐year period was 51 patients (95% CI, 31‐103).

CONCLUSIONS:

In men with prostate cancer, pelvic 3‐D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short‐course AST to EBRT. This risk associated with EBRT must be site‐specific as there was no increase in the risk of fall‐related fractures in bones that were outside the radiation field. Cancer 2011. © 2011 American Cancer Society.     

Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality

BACKGROUND: For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA) recurrence, whether the time to an undetectable (u) PSA was significantly associated with prostate cancer-specific mortality (PCSM) was evaluated. METHODS: The study cohort comprised 585 men with a rising PSA and negative bone scan after surgery (n = 415) or radiation therapy (n = 170) that were treated with AST and achieved a uPSA. Gray's regression was used to evaluate whether the time to a uPSA after AST was significantly associated with the time to PCSM after the uPSA adjusting for known prognostic factors. RESULTS: The median time (interquartile range) to achieve a uPSA was 4.6 (range, 2.8-7.8) months. There were 23 deaths, 4 of which were from prostate cancer. An increasing time to a uPSA (adjusted hazard ratio [HR]: 9.2, 95% confidence interval [CI]: 3.8, 22.1; P < .0001), a decreasing PSA doubling time (DT) (HR: 0.58, 95% CI: 0.43, 0.80; P = .0007), and Gleason score 8 to 10 cancers (HR: 8.6, 95% CI: 1.04, 77; P = .05) were significantly associated with a shorter time to PCSM. CONCLUSIONS: Despite achieving a uPSA after AST, the risk of PCSM increased significantly as the time to the uPSA lengthens, especially in men with a short pre-AST PSA DT and high-grade prostate cancer. These men should be considered for randomized studies evaluating immediate vs delayed chemotherapy after the achievement of the uPSA.     

Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

The uncertain relationship between obesity and prostate cancer: an Italian biopsy cohort analysis

Background

The study aims to investigate the relationship between obesity and prostate cancer diagnosis at biopsy.

Methods

From 2005 onwards, a consecutive series of patients undergoing 12-core prostate biopsy for PSA value ≥ 4 ng/ml and/or positive digital rectal examination (DRE) were enrolled. Before the biopsy, patients underwent a physical examination, including height and weight measurement. Obesity was defined as body mass index (BMI) ≥30 kg/m². Blood samples were drawn from all patients and analyzed for total PSA and testosterone.

Results

885 patients were enrolled with a median age and PSA of 67 years (range 37-95) and 6.4 ng/ml (range 1-30) respectively. Median BMI was 27.1 kg/m² (range 18-46.6) with 185 patients classified as obese. 363 patients had cancer at biopsy; 76 were obese. PSA was independently associated with a higher risk of cancer (OR 1.09 per 1 unit PSA, p = 0.01). On multivariate analysis, the BMI was not significantly associated with an increased prostate cancer risk (p = 0.19). Out of 363 patients with prostate cancer, 154 had a Gleason score 6 (23 were obese) and 209 a Gleason score ≥7 (53 were obese). Among men with cancer, a higher BMI on univariate (p = 0.001) and multivariate analysis (p = 0.005) was associated with high-grade disease (Gleason ≥ 7).

Conclusions

In our single center study and less aggressively screened cohort, obesity is associated with an increased risk of a high-grade Gleason score when prostate cancer is diagnosed at biopsy.     

Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy.

PURPOSE: We evaluated predictors of prostate cancer-specific mortality (PCSM) after prostate-specific antigen (PSA) failure after radical prostatectomy (RP) or radiation therapy (RT). PATIENTS AND METHODS: A total of 1,159 men with clinically localized prostate cancer treated with RP (n = 498) or RT (n = 661) developed PSA failure, and they formed the study cohort. Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis, including post-treatment PSA doubling time (PSA-DT), Gleason score, and interval to PSA failure, could also predict time to PCSM after PSA failure. The cumulative incidence method was used to estimate PCSM after PSA failure. RESULTS: A post-RP PSA-DT of less than 3 months (hazard ratio [HR], 54.9; 95% CI, 16.7 to 180), a post-RT PSA-DT of less than 3 months (HR, 12.8; 95% CI, 7.0 to 23.1), and a biopsy Gleason score of 8 to 10 (HR, 6.1; 95% CI, 3.4 to 10.7) for patients treated with RT were significantly associated with PCSM. Post-RP estimated rates of PCSM 5 years after PSA failure were 31% (95% CI, 17% to 45%) v 1% (95% CI, 0% to 2%) for patients with PSA-DT of less than 3 months v > or = 3 months. Post-RT estimated rates of PCSM 5 years after PSA failure were 75% (95% CI, 59% to 92%) v 35% (95% CI, 24% to 47%) for patients with a biopsy Gleason score of > or = 8 v < or = 7, respectively, and PSA-DT of less than 3 months; these rates were 15% (95% CI, 0.8% to 28%) v 4% (95% CI, 1% to 6%), respectively, for patients with a PSA-DT > or = 3 months. CONCLUSION: Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score. These parameters may be useful in identifying patients for a randomized trial evaluating hormonal therapy with or without docetaxel.     

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.     

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: A systematic review

Background and Purpose

For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be given by dose-escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR) brachytherapy (EBTI). Differences in outcome between the modalities were assessed by a systematic review.

Materials and methods

A systematic search was performed resulting in 40 articles to be used. Data were extracted on biochemical control and overall survival at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. Comparison of the modalities was done by a Weibull survival analysis and estimation of Hazard Ratio’s (HR) was done with 95% confidence intervals (95% CIs).

Results

The HR for biochemical recurrence was 1.40 (95% CI 1.31-1.51) for EBRT relative to EBTI, and was 1.37 (95% CI 1.26-1.49) for EBSeeds relative to EBTI. The HR for overall survival was 1.50 (95% CI 1.29-1.73) for EBRT relative to EBTI, and was 2.33 (95% CI 2.04-2.66) for EBSeeds relative to EBTI.

Conclusion

The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer.     

A multi-institutional analysis comparing adjuvant and salvage radiation therapy for high-risk prostate cancer patients with undetectable PSA after prostatectomy

Background and purpose

In men with adverse pathology at the time of radical prostatectomy (RP), the most appropriate timing to administer radiotherapy (RT) remains a subject for debate. To determine whether salvage radiotherapy (SRT) upon early prostate-specific antigen (PSA) relapse is equivalent to immediate adjuvant radiotherapy (ART) post RP.

Material and methods

130 patients receiving ART and 89 receiving SRT were identified. All had an undetectable PSA after RP. Homogeneous subgroups were built based on the status (±) of lymphatic invasion (LVI) and surgical margins (SM), to allow a comparison of ART and SRT. Biochemical disease-free survival (bDFS) was calculated from the date of surgery and from the end of RT. The multivariate analysis was performed using the Cox Proportional hazard model.

Results

In the SM−/LVI− and SM+/LVI− groups, SRT was a significant predictor of a decreased bDFS from the date of surgery, while in the SM+/LVI+ group, there was a trend towards significance. From the end of RT, SRT was also a significant predictor of a decreased bDFS in three patient groups: SM−/LVI−, SM+/LVI− and SM+/LVI+. Gleason score >7 showed to be another factor on multivariate analysis associated with decreased bDFS in the SM−/LVI− group, from the date of surgery and end of RT. Preoperative PSA was a significant predictor in the SM−/LVI− group from the date of RP only.

Conclusions

Immediate ART post RP for patients with high risk features in the prostatectomy specimen significantly reduces bDFS after RP compared with early SRT upon PSA relapse.     

Late toxicity after postprostatectomy salvage radiation therapy

Purpose

To evaluate late toxicity in patients who received salvage external beam radiotherapy (EBRT) for a detectable prostate-specific antigen (PSA) level after radical prostatectomy (RP).

Methods

A cohort of 308 consecutive patients underwent salvage EBRT from July 1987 through June 2003 for a detectable PSA level after RP. All were treated with high-energy photons (6-20 MV) to a median dose of 64.8 Gy (range: 54.0-72.4 Gy) in 1.8- to 2.0-Gy fractions.

Results

Median follow-up from the completion of EBRT was 60 months (range: 1 day-174 months). Late toxicity occurring more than 90 days after EBRT completion was identified in 41 patients (13%). Twelve patients (3.9%) had grade 2 urethral strictures and were treated with urethral dilation, 3 patients had grade 3 cystitis, and 1 had a grade 4 rectal complication. These numbers correspond to an estimated 0.7% (95% confidence interval, 0.0-1.6%) of patients experiencing a grade 3 or 4 complication by 5 years after the start of EBRT.

Conclusions

Salvage EBRT for a detectable PSA level after RP is the only curative treatment in this setting. This treatment can be administered in a manner that results in a low likelihood of late complications.     

The Cancer of the Prostate Risk Assessment (CAPRA) in patients treated with external beam radiation therapy: Evaluation and optimization in patients at higher risk of relapse

Background

The Cancer of the Prostate Risk Assessment (CAPRA) was developed to predict freedom from biochemical failure (FFBF) following radical prostatectomy (RP). Its utility following external beam radiation therapy (EBRT) has not been externally evaluated.

Methods

A retrospective study of 612 patients treated with dose-escalated EBRT at the University of Michigan Medical Center.

Results

Compared to the derivation cohort, EBRT treated patients had higher-risk disease (28% with CAPRA of 6-10 vs. 5%, respectively). A total of 114 patients (19%) had BF with 5-year BF ranging from 7% with CAPRA 0-3 to 35% with CAPRA 7-10. For RT patients the risk of BF at 5-year was similar to 4 surgical cohorts for CAPRA scores 0-2 but lower for all CAPRA scores ? 3. The difference favoring RT increased with increasing CAPRA score reaching a 27-50% absolute improved at 5-years for CAPRA scores of 6-10. On multivariate analysis each CAPRA point increased the risk of BF (p < 0.0001) while Gleason pattern 5 in the biopsy also increased BF (p = 0.01) and long-term androgen deprivation therapy (ADT) significantly reduced the risk of BF (p = 0.015).

Conclusions

Compared to surgical series the risk of BF was lower with dose-escalated EBRT with the greatest difference at the highest CAPRA scores.     

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone

Purpose

Intermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients.

Material and methods

Eighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7 mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA + 2 ng/mL.

Results

With a median follow-up of 51 months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ?2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity.

Conclusion

HyRT to a dose of 66 Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.