Significant Predictors Of Biochemical Failure Research Articles

Single-fraction HDR brachytherapy as monotherapy in low and intermediate risk prostate cancer: Outcomes from two clinical trials with and without an MRI-guided boost

PurposeSingle-fraction HDR monotherapy for the treatment of localized prostate cancer is appealing, but published outcomes are discouraging. An approach to improve local control is MRI-guided focal dose-escalation to the dominant intraprostatic lesion (DIL). Here we report a comparison of outcomes from two phase II clinical trials with and without a focal boost. MethodsPatients had low or intermediate-risk disease. Patients in Trial1 received a single 19 Gy HDR implant to the whole prostate. Trial2 incorporated an additional MRI-guided focal DIL boost to at least 23 Gy. ADT was not allowed. Toxicities (CTCAEv4.0) and quality of life (EPIC) were collected. Biochemical failure (BF) was defined as nadir +2. Univariate and multivariate logistic regression analysis was conducted to search for predictors of BF. ResultsTrial1 had 87 patients with a median follow-up of 62 months, while Trial2 had 60 patients with a median follow-up of 50 months. The five-year cumulative BF rate was 32.6% and 31.3%, respectively (p = 0.9). 77.5% of failures were biopsy-confirmed local failures, all of which underwent local salvage therapy. The addition of a DIL boost was not associated with worse toxicity or QOL. Baseline PSA and Gleason score correlated with BF, but none of the dosimetric parameters was a significant predictor of BF. ConclusionsMRI-guided focal boost was safe and well tolerated, but did not improve local control after 19 Gy single-fraction HDR monotherapy, and the control rates were unacceptable. Single-fraction HDR monotherapy for prostate cancer should not be offered outside of clinical trials.

Multi-Institutional Analysis of Prostate-Specific Antigen Kinetics After Stereotactic Body Radiation Therapy

Understanding prostate-specific antigen (PSA) kinetics after radiation therapy plays a large role in the management of patients with prostate cancer (PCa). This is particularly true in establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiation therapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT. PSA data from 5 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2004 to 2016. Patients received 35 to 40 Gy in 5 fractions, per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models were developed to identify significant predictors of time to biochemical failure. A total of 1062 patients were included in this study. Median follow-up was 66 months (interquartile range [IQR], 36.4-89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/mL, median time to nPSA was 40 months, 84% of patients had an nPSA ≤0.5 ng/mL, and 54% of patients had an nPSA ≤0.2 ng/mL. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/mL (IQR, 0.3-1.0 ng/mL). Median time to PSA bounce was 18.1 months (IQR, 12.0-31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. Joint latent class models modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure. In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.

Radical prostatectomy and the effect of close surgical margins: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

To evaluate biochemical recurrence (BCR) patterns amongst men undergoing radical prostatectomy (RP) with specimens having negative (NSM), positive (PSM), and close surgical margins (CSM) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM, PSM, and CSM. CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate-specific antigen (PSA) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR, metastases, and mortality were analysed using Cox proportional hazard models. Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM, 1902 (44%) had PSM, and 372 (8%) had CSM. On multivariable analysis, relative to NSM, men with CSM had a higher risk of BCR (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.25-1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM (HR 2.09, 95% CI 1.86-2.36; P < 0.001). Metastases, prostate cancer-specific mortality and all-cause mortality did not differ based on margin status alone. Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.

Curative brachytherapy for prostate cancer in African-Caribbean patients: A retrospective analysis of 370 consecutive cases

PurposeProstate cancer is the most frequent malignancy in African-Caribbean men, a population sharing common genetic traits with African-American (AA) but presenting also genomic and epidemiologic specificities. Despite socioeconomic disparities with French mainland, all patients were treated within the French state–financed equal-access health care system. In this study, we report biochemical outcomes of patients treated by brachytherapy in our department from 2005 to 2014 in an African-Caribbean population. Methods and MaterialsThree hundred seventy consecutive patients receiving 125I brachytherapy as a curative treatment for early-stage (localized) disease between 2005 and 2014 were recorded. Selected patients presented with low-risk disease: initial prostate-specific antigen (PSA) <10 ng/mL, clinical stage ≤ T2c, and Gleason score <7. Patients with intermediate risk of recurrence were also included on a case-to-case basis with prostate-specific antigen <15 or Gleason score 7 (3 + 4). Biochemical failure free–survival was defined according to the American Society for Radiation Oncology nadir+2 definition. ResultsThe 3-year and 5-year biochemical failure free–survival for the entire cohort were 98.3% and 91.6%, respectively. For patients with low- and intermediate-risk disease, the 5-year BBFS rates were 92.1% and 90.8%, respectively. In univariate and multivariate analyses, only Gleason score (<7 vs. 7; p = 0.030 vs. p < 0.05) was a significant predictor of biochemical failure. The overall rate of late and acute Grade 2 or higher genitourinary toxicity was 12.6% and 10.3%. ConclusionsIn this large single-center series, brachytherapy achieved excellent rates of medium-term biochemical control in both low and selected intermediate-risk localized prostate cancer in African-Caribbean patients. Brachytherapy seems to be an excellent choice of treatment, with excellent outcomes and limited morbidity for African-Caribbean populations.

A retrospective analysis after low-dose-rate prostate brachytherapy with permanent (125)I seed implant: clinical and dosimetric results in 70 patients.

To evaluate the biochemical disease-free survival (bDFS) rate after (125)I permanent-implant prostate brachytherapy. Patients with a diagnosis of prostate adenocarcinoma and adequate PSA follow-up were selected for this retrospective study. Brachytherapy with permanent (125)I seeds was performed as monotherapy, with a prescribed dose of 145 Gy to the prostate. Patients were stratified into recurrence risk groups according to the National Comprehensive Cancer Network (NCCN) guidelines. Biochemical failure was defined using the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. The post-implant D90 (defined as the minimum dose covering 90% of the prostate) was obtained for each patient. Two cutoff points were used to test the correlation between D90 and bDFS results: 130 Gy and 140 Gy. bDFS was calculated from the implant date to the date of biochemical recurrence. Univariate and multivariate analysis were performed using the SPSS software and included clinical stage, pretreatment PSA, Gleason score (GS), androgen deprivation therapy, D90, and risk groups. In the univariate analysis we used a cutoff point of 5.89 ng/mL for PSA and 5 for GS. From June 2003 to April 2007, 70 patients were analyzed. The patients' distribution into recurrence risk groups was as follows: 39 patients (56%) in the low-risk group, 23 patients (33%) in the intermediate-risk group, and 8 patients (11%) in the high-risk group. At a median follow-up of 47 months (range, 19-70 months) bDFS was 88.4%, with a global actuarial 5-year bDFS of 86%. Disease-related factors including initial PSA level, GS and risk group were significant predictors of biochemical failure ( P = 0.01, P = 0.01, P = 0.006, respectively). In multivariate analysis, risk group (P = 0.005) and GS (P = 0.03) were statistically significant. Our data are in agreement with those in the literature and, despite the short follow-up, confirm the advantage of brachytherapy for patients at low and intermediate risk of recurrence.

Prostate brachytherapy as salvage for local failure after external beam radiation.

125 Background: Local failure (LF) after external beam radiation (EBRT) for prostate cancer is a serious problem. Most patients receive non-curative androgen deprivation therapy (ADT), but there is a subset with LF who are still potentially curable. There is limited evidence to suggest that prostate brachytherapy (BT) is an effective, potentially curative salvage therapy with acceptable toxicity. We hypothesize that salvage BT following EBRT can achieve high rates of biochemical control with acceptable toxicity. Methods: We analyzed 39 consecutive patients treated from 1998-2013 with salvage BT at 2 centers. All patients had pathologically confirmed LF following previous EBRT without distant mets &amp; a disease-free interval of ≥ 18-24 mo. Salvage BT to the whole prostate was delivered to 29 patients using low-dose rate I-125 or Pd-103 seed implants (median dose 100 Gy with Pd-103) while 10 received HDR BT (median 30 Gy in 6 fractions). Cases were planned as if de novo but to a lower dose. 33 (85%) received neoadjuvant and/or adjuvant ADT as part of their salvage therapy. Biochemical failure (BF) was defined using the Phoenix criteria. Risk factor analysis was conducted to identify characteristics that predict BF after salvage BT. Results: For the 39 patients, median PSA at diagnosis was 8.4, and 21 (54%) had high-risk disease. Median EBRT dose was 70 Gy with 11 patients (28%) receiving ADT. Median PSA nadir following EBRT was 0.8 (range 0 – 2.6). Median time to recurrence was 53 mo (range 18 – 150), and median pre-salvage PSA was 4.8. Median follow-up after salvage BT was 60.1 mo (range 7 – 150). Biochemical failure-free survival, DMFS and OS at 5 &amp; 7 yrs were 76% &amp; 67%; 91% &amp; 85% and 92% &amp; 84%, respectively. On univariate analysis, PSA nadir after EBRT &amp; pre-salvage PSA were significant predictors of BF (p&lt; 0.01 for both). On multivariate analysis, only pre-salvage PSA was a significant independent predictor of BF (p&lt; 0.01). Freedom from late grade 3 GU toxicity at 3 yrs was 83%. There were no late Grade 3 GI toxicities. Conclusions: This is the largest series reporting on salvage prostate brachytherapy plus ADT for local-only failures after EBRT &amp; suggests that salvage BT with ADT offers selected patients prolonged disease-free survival with acceptable toxicity.

Prostate brachytherapy in Ghana: our initial experience.

PurposeThis study presents the experience of a brachytherapy team in Ghana with a focus on technology transfer and outcome. The team was initially proctored by experienced physicians from Europe and South Africa.Material and methodsA total of 90 consecutive patients underwent either brachytherapy alone or brachytherapy in combination with external beam radiotherapy for prostate carcinoma between July 2008 and February 2014 at Korle Bu Teaching Hospital, Accra, Ghana. Patients were classified as low-risk, intermediate, and high-risk according to the National Comprehensive Cancer Network (NCCN) criteria. All low-risk and some intermediate risk group patients were treated with seed implantation alone. Some intermediate and all high-risk group patients received brachytherapy combined with external beam radiotherapy.ResultsThe median patient age was 64.0 years (range 46-78 years). The median follow-up was 58 months (range 18-74 months). Twelve patients experienced biochemical failure including one patient who had evidence of metastatic disease and died of prostate cancer. Freedom from biochemical failure rates for low, intermediate, and high-risk cases were 95.4%, 90.9%, and 70.8%, respectively. Clinical parameters predictive of biochemical outcome included: clinical stage, Gleason score, and risk group. Pre-treatment prostate specific antigen (PSA) was not a statistically significant predictor of biochemical failure. Sixty-nine patients (76.6%) experienced grade 1 urinary symptoms in the form of frequency, urgency, and poor stream. These symptoms were mostly self-limiting. Four patients needed catheterization for urinary retention (grade 2). One patient developed a recto urethral fistula (grade 3) following banding for hemorrhoids.ConclusionsOur results compare favorably with those reported by other institutions with more extensive experience. We believe therefore that, interstitial permanent brachytherapy can be safely and effectively performed in a resource challenged environment if adequate training and proctoring is provided.

Positive resection margins may not reflect the true margin in patients undergoing radical prostatectomy

The aim of the present study was to evaluate the hypothesis that a positive resection margin (RM1) of an excised specimen may not reflect the true margin in patients that have undergone radical prostatectomy (RP). Between September 2003 and March 2011, 370 Japanese patients underwent an antegrade RP at the National Kyushu Cancer Center (Fukuoka, Japan), however, 95 of these patients were excluded from the study due to a history of receiving hormonal therapy or insufficient preoperative clinical data. The incidence of biochemical failure (BCF) was evaluated using multivariate analysis, which revealed that the preoperative prostate-specific antigen (PSA) level, pathological tumor stage, RP Gleason score and a PSA nadir <0.008 ng/ml were significant predictors (P=0.0065, 0.0006, 0.0002 and <0.0001, respectively). By contrast, an RM1 was not found to be a significant predictor of BCF, while the parameter with the highest hazard ratio (HR) was a PSA nadir <0.008 ng/ml (HR, 10.055; 95% confidence interval, 5.005–20.200). From the 56 cases that were RM1, 41 cases (73.2%) exhibited a PSA nadir <0.008 ng/ml. There were 42 cases (75.0%) in which only one site was identified to be RM1; among these cases, no significant difference was observed between a PSA level <0.008 ng/ml and a PSA level ≥0.008 ng/ml at the RM1 site (apex, P=0.1460; base, P=0.1384; anterior, P=0.3870; and posterolateral, P=0.5040). There were 14 cases (25.0%) in which multiple sites were RM1; these cases were classified by the number of sites that were RM1 (one vs. multiple) and no significant difference was observed between a PSA level <0.008 ng/ml and a PSA level ≥0.008 ng/ml (P=0.6090). Based on these results, an RM1 of an excised specimen may not reflect the true margin in patients that are treated with RP, specifically in cases where the PSA level is identified to decrease to below the postoperative measurement threshold value (PSA nadir <0.008 ng/ml).

Usefulness of ultra-sensitive prostate-specific antigen following radical prostatectomy.

This study aimed to evaluate the usefulness of ultra-sensitive prostate-specific antigen (PSA) following radical prostatectomy (RP). Between September, 2003 and March, 2009, a total of 311 prostate cancer patients underwent antegrade RP; following the exclusion of 111 patients due to prior hormonal therapy, 200 patients were finally included in this study. The results of the multivariate analysis identified RP Gleason score, extraprostatic extension, lymph node metastasis and PSA nadir as significant predictors of biochemical failure (P=0.0116, 0.0216, 0.0178 and <0.0001, respectively) and PSA nadir <0.008 ng/ml exhibited the highest hazard ratio (HR) [HR=26.34; 95% confidence interval (CI): 7.34-104.69]. After a median follow-up period of 52.2 months, the biochemical failure-free rate in the PSA nadir <0.008 and ≥0.008 ng/ml groups was 94.3 and 58.8%, respectively, with a statistically significant difference according to the log-rank test (P<0.001). In the multivariate analysis, statistically significant differences were observed only in pathological nodel stage within the PSA nadir <0.008 ng/ml group (P=0.0107). For this reason, postoperative follow-up using ultra-sensitive PSA is considered to be of value, since the use of high-sensitivity PSA to confirm a reduction to below postoperative measurement threshold value (PSA nadir <0.008 ng/ml) may avert administering unnecessary additional treatment, regardless of pathological reccurrence factors.

The Prognostic Value of Percentage of Positive Biopsy Cores, Percentage of Cancer Volume, and Maximum Involvement of Biopsy Cores in Prostate Cancer Patients Receiving Proton and Photon Beam Therapy

The purpose of this study was to compare the prognostic value of the percentage of positive biopsy cores (PPBC), the percentage of cancer volume (PCV), and the maximum involvement of biopsy cores (MIBC) as a prognostic factor in low- and intermediate-risk patients with clinically localized prostate cancer who received proton or photon beam therapy. Four hundred and fifty-nine patients with clinically localized prostate carcinoma who were treated with proton or photon beam therapy at Loma Linda University Medical Center were used for this analysis. Patients were treated with a median dose of 74.0 Gy (range 70.2-79.2) proton or combined proton/photon beam radiotherapy. Pathology reports were reviewed and PPBC, PCV, and MIBC were recorded. Analysis of biochemical no evidence of disease (bNED) outcome was assessed using Kaplan-Meier analyses. Cox regression multivariate analyses were performed to assess the impact of the biopsy factors on survival. 285, 291, and 291 patients had biopsy information available for analysis, respectively. Survival analysis showed that a higher PPBC, PCV, and MIBC were each individually associated with an increased risk of biochemical failure on univariate analysis (p < 0.01). Only PPBC and PCV were associated with an increased risk of biochemical failure on multivariate analysis, adjusting for age, NCCN risk group, and dose (p < 0.01). When isolating the intermediate-risk group, only PPBC and PCV were statistically significant on multivariate analysis. Multivariate analysis of the intermediate-risk group comparing PPBC and PCV showed that PPBC was not a significant predictor of biochemical failure, while PCV was a significant predictor of biochemical failure (p = 0.37 and p = 0.03, respectively). PPBC and PCV can potentially be used for additional risk stratification of intermediate-risk patients with PCV potentially being the most clinically relevant predictor bNED survival. MIBC was not found to have utility in the prognosis of low- and intermediate-risk patients.

Impact of Percentage of Positive Biopsy Cores on Biochemical Outcome in Patients Treated With Low-Dose Rate (Iodine-125) Brachytherapy for Prostate Cancer

To investigate the significance of the percentage of positive biopsy cores (PPBCs) in predicting the biochem- ical outcome in patients with clinically localised prostate cancer undergoing low-dose rate brachytherapy (LDRB).  A total of 326 consecutive patients underwent LDRB between February 1997 and January 2007. The cohort consisted of 68.7%, 30.4% and 0.9% of low-, intermediate- and high-risk groups respectively as defined by the D'Amico classifica- tion. Patients were stratified according to PPBCs ( 50%).  Of the 326 men, 316 (97%) met the study criteria and were included in the analysis. The median follow-up was 66.3 (12.9-147.5) months. Thirty-eight men (12%) developed evidence of biochemical relapse as defined by the Phoenix defi- nition at a median of 44.5 (4-133) months. The overall 5-year and 10-year biochemical relapse-free rate (BRFR) was 91.9% (95% CI 87.9% to 94.6%) and 76.9% (95% CI 66% to 84%) respectively.  On univariate analysis, Gleason score (p=0.03), D'Amico risk groups (p=0.004) and PPBCs (p=0.001) were significant predictors of biochemical failure. In the multivariate model, the PPBCs (p=0.0006) and pretreatment PSA (p=0.004) were the only variables that predicted for biochemical failure. The 5-year biochemical relapse-free rate was 93.5%, 93.0% and 76.5% for the PPBCs 50% respectively (p=0.001). Conclusions:  The PPBC is an important independent predictor of the 5-year biochemical relapse-free survival after LDRB. This finding suggests that patients with high volume tumour are at increased risk of biochemical failure with LDRB.

Impact of Neoadjuvant Prostate-Specific Antigen Kinetics on Biochemical Failure and Prostate Cancer Mortality: Results From a Prospective Patient Database

To confirm findings from an earlier report showing that neoadjuvant (NA) prostate-specific antigen (PSA) halving time (PSAHT) impacts biochemical failure (BF) rates, and to examine its association with prostate cancer-specific survival (PCSS), in a large prospective cohort of patients. A total of 502 patients were selected from a prospective database, who had localized prostate adenocarcinoma treated with 2-12 months of neoadjuvant androgen deprivation therapy (N-ADT) followed by external beam radiation therapy (EBRT) between 1994 and 2000, and had at least 2 NA PSA values. Seventy-four percent of patients had high-risk prostate cancer. Median initial PSA value, N-ADT duration, total ADT duration, and radiation therapy dose were 14 ng/mL, 6.9 months, 10.8 months, and 68 Gy, respectively. At a median follow-up of 9.9 years, 210 patients have had a BF. Median PSAHT was 18 days. On univariate analysis, PSAHT was not shown to predict for BF (P=.69) or PCSS (P=.28). However, NA nadir PSA (nanPSA) and post-therapy nadir PSA (ptnPSA), when analyzed as continuous or categoric variables, predicted for BF (P<.001) and PCSS (P<.001). On multivariate analysis, nanPSA (P=.037) and ptnPSA (P<.001) continued to be significantly associated with BF. However, N-ADT duration lost significance (P=.67), and PSAHT remained a nonsignificant predictor (P=.97). For PCSS, multivariate analysis showed nanPSA (P=.049) and ptnPSA (P<.001) to be significant. Again PSAHT (P=.49) remained nonsignificant. In this large, prospective cohort of patients, NA PSA kinetics, expressed as PSAHT, did not predict BF or PCSS. However, nadir PSAs, in both the NA and post-therapy settings, were significant predictors of BF and PCSS. Optimization of therapy could potentially be based on early PSA response, with shorter durations of ADT for those predicted to do favorably, and intensification of therapy for those likely to have poorer outcomes.

Gleason 7 prostate cancer treated with low‐dose‐rate brachytherapy: lack of impact of primary Gleason pattern on biochemical failure

What's known on the subject? and What does the study add? There appears to be a clear difference in cancer control outcomes for patients with Gleason scores of 3+4 and those with scores of 4+3 after radical prostatectomy. It has been documented that patients with Gleason 4+3 prostate cancer have higher incidences of non-organ-confined disease than those with primary pattern 3. Higher rates of extracapsular extension, seminal vesicle invasion and positive margins have been found to be associated with primary pattern 4 over 3. These higher rates of non-organ-confined disease can lead to increased biochemical failure, which, in turn, can lead to higher mortality rates. This study provides information on the prognostic significance of primary Gleason pattern in the brachytherapy management of prostate cancer. Study Type - Prognosis (case series) Level of Evidence 4. • To report the biochemical outcomes for Gleason 7 prostate cancer treated with brachytherapy. • To analyse the impact of the primary Gleason pattern as well as other disease- and treatment-related factors on outcome. • A total of 560 patients with Gleason 7 prostate cancer were treated between 1990 and 2008 with brachytherapy, alone or in combination with hormonal therapy and/or external beam radiation therapy. • There were 352 patients with Gleason pattern 3+4 and 208 with Gleason pattern 4+3. • The mean (range) presenting PSA level was 11.2 (1-300) ng/mL, and the median was 7.8 ng/mL. • The presenting clinical stages were T1b in 1%, T1c in 33%, T2a in 16%, T2b in 32%, T2c in 16% and T3 in 2% of patients. • The actuarial freedom from biochemical failure rate at 10 years was 82%. • There was no significant difference between 10-year freedom from biochemical failure rates for patients with Gleason scores of 3+4 (79%) and those with scores of 4+3 (82%). • Biologically effective dose and presenting PSA level were both significant predictors of biochemical failure in multivariate analysis. • The primary Gleason pattern in Gleason 7 prostate cancer shows no significant effect on biochemical failure when treated with brachytherapy. • These results are different from those found after radical prostatectomy and are probably attributable to the enhanced local control afforded by a brachytherapy approach to this disease subset.

A retrospective analysis after low-dose-rate prostate brachytherapy with permanent 125I seed implant: clinical and dosimetric results in 70 patients

To evaluate the biochemical disease-free survival (bDFS) rate after (125)I permanent-implant prostate brachytherapy. Patients with a diagnosis of prostate adenocarcinoma and adequate PSA follow-up were selected for this retrospective study. Brachytherapy with permanent (125)I seeds was performed as monotherapy, with a prescribed dose of 145 Gy to the prostate. Patients were stratified into recurrence risk groups according to the National Comprehensive Cancer Network (NCCN) guidelines. Biochemical failure was defined using the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. The post-implant D90 (defined as the minimum dose covering 90% of the prostate) was obtained for each patient. Two cutoff points were used to test the correlation between D90 and bDFS results: 130 Gy and 140 Gy. bDFS was calculated from the implant date to the date of biochemical recurrence. Univariate and multivariate analysis were performed using the SPSS software and included clinical stage, pretreatment PSA, Gleason score (GS), androgen deprivation therapy, D90, and risk groups. In the univariate analysis we used a cutoff point of 5.89 ng/mL for PSA and 5 for GS. From June 2003 to April 2007, 70 patients were analyzed. The patients' distribution into recurrence risk groups was as follows: 39 patients (56%) in the low-risk group, 23 patients (33%) in the intermediate-risk group, and 8 patients (11%) in the high-risk group. At a median follow-up of 47 months (range, 19-70 months) bDFS was 88.4%, with a global actuarial 5-year bDFS of 86%. Disease-related factors including initial PSA level, GS and risk group were significant predictors of biochemical failure ( P = 0.01, P = 0.01, P = 0.006, respectively). In multivariate analysis, risk group (P = 0.005) and GS (P = 0.03) were statistically significant. Our data are in agreement with those in the literature and, despite the short follow-up, confirm the advantage of brachytherapy for patients at low and intermediate risk of recurrence.

THE NUMBER OF NEGATIVE PELVIC LYMPH NODES REMOVED DOES NOT AFFECT THE RISK OF BIOCHEMICAL FAILURE AFTER RADICAL PROSTATECTOMY

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVES To assess patients who had radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for pT2–4 N0M0 prostate cancer, to determine if LN yield affects the risk of biochemical failure (BCF), as the extent of PLND at the time of RP has become increasingly uncertain with the decreasing trend in tumour stage. PATIENTS AND METHODS We reviewed the Columbia University Urologic Oncology Database for patients with pT2–4 N0M0 prostate cancer treated with RP from 1990 to 2005. Exclusion criteria included <12 months of follow-up, incomplete clinical and pathological data, and neoadjuvant androgen-deprivation therapy (ADT) or immediate adjuvant ADT or external beam radiotherapy. Unadjusted and adjusted models were used to determine the ability of clinical and pathological variables to predict BCF. RESULTS The final dataset included 964 patients, with a mean age of 60.5 years and median preoperative prostate-specific antigen (PSA) level of 6.2 ng/mL. The median (range) LN yield was 7 (1–42) and the median follow-up 59 (12–190) months. In the unadjusted and adjusted models, preoperative PSA, pathological Gleason score, pathological stage, surgical margin status and year of surgery were significant predictors of BCF. The LN group was not a significant predictor of BCF in both the unadjusted and adjusted model (P = 0.759 and 0.408, respectively). When patients were stratified into high- and low-risk groups, LN yield remained an insignificant predictor of BCF. CONCLUSION A higher LN yield at the time of RP does not increase the chance of cure for patients with pT2–4N0M0 prostate cancer. This lack of a survival advantage holds true for patients with high-risk disease.

The number of negative pelvic lymph nodes removed does not affect the risk of biochemical failure after radical prostatectomy

To assess patients who had radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for pT2-4 N0M0 prostate cancer, to determine if LN yield affects the risk of biochemical failure (BCF), as the extent of PLND at the time of RP has become increasingly uncertain with the decreasing trend in tumour stage. We reviewed the Columbia University Urologic Oncology Database for patients with pT2-4 N0M0 prostate cancer treated with RP from 1990 to 2005. Exclusion criteria included <12 months of follow-up, incomplete clinical and pathological data, and neoadjuvant androgen-deprivation therapy (ADT) or immediate adjuvant ADT or external beam radiotherapy. Unadjusted and adjusted models were used to determine the ability of clinical and pathological variables to predict BCF. The final dataset included 964 patients, with a mean age of 60.5 years and median preoperative prostate-specific antigen (PSA) level of 6.2 ng/mL. The median (range) LN yield was 7 (1-42) and the median follow-up 59 (12-190) months. In the unadjusted and adjusted models, preoperative PSA, pathological Gleason score, pathological stage, surgical margin status and year of surgery were significant predictors of BCF. The LN group was not a significant predictor of BCF in both the unadjusted and adjusted model (P = 0.759 and 0.408, respectively). When patients were stratified into high- and low-risk groups, LN yield remained an insignificant predictor of BCF. A higher LN yield at the time of RP does not increase the chance of cure for patients with pT2-4N0M0 prostate cancer. This lack of a survival advantage holds true for patients with high-risk disease.

Correlation of hypoxic prostate/muscle pO2 (P/M PO2) ratio and biochemical failure in patients with localized prostate cancer: Long-term results

5136 Background: Tumor hypoxia may confer radioresistance in prostate cancer. The purpose of this study was to correlate tumor oxygenation status with long term biochemical outcome following prostate bracytherapy. Methods: Custom made Eppendorf PO2 microelectrodes were used to obtain PO2 measurements from the prostate (P), focused on + biopsy locations, and normal muscle tissue (M), as a control, in the operating room using a sterile technique. A total of 11,516 measurements were obtained in 57 patients with localized prostate cancer immediately prior to prostate brachytherapy. The Eppendorf histograms provided the median PO2, mean PO2, and % &lt; 5 mm Hg or &lt; 10 mm Hg. All patients received brachytherapy implants (48 low dose rate and 9 high dose rate) and five patients had received prior hormonal therapy. Biochemical failure (BF) was defined using both the newer Phoenix (PSA nadir + 2 ng/mL) the prior ASTRO (three consecutive rises) definitions (dfn). A Cox proportional hazards regression model evaluated the influence of hypoxia on BF with P/M ratio as a continuous variable and dichotomized at 0.05, 0.10, and 0.20. Results: The median follow-up was 8 years (range: 0.8- 9.4 years). Twelve patients developed BF via ASTRO dfn and 8 via Phoenix dfn. On stepwise multivariate analysis, P/M ratio &lt; 0.10 was a significant predictor of BF (ASTRO, p = 0.03; Phoenix p = 0.02) in a model including initial PSA, Gleason score, T-stage, perineural invasion, age, hemoglobin and use of hormonal therapy. Kaplan-Meier freedom from BF for P/M ratio &lt; 0.10 vs. ≥ 0.10 at 8 years was 46% vs 78% (p = 0.03) for the ASTRO dfn and 66% vs 83% (p = 0.02) for the Phoenix dfn. Only one patient (in the P/M ratio &lt; 0.10) manifested distant failure. Conclusions: Hypoxia in prostate cancer (low P/M PO2 ratio) significantly predicts for poor long term biochemical outcome on multivariate analysis, suggesting that novel hypoxic strategies should be investigated. No significant financial relationships to disclose.

The relationship between preoperative prostate‐specific antigen and biopsy Gleason sum in men undergoing radical retropubic prostatectomy: a novel assessment of traditional predictors of outcome

To investigate the relationship between prostate-specific antigen (PSA) level and Gleason sum, and its impact on biochemical failure (persistent PSA level of >0.2 ng/mL) after radical prostatectomy (RP), as the PSA, Gleason sum and clinical stage are commonly used preoperative predictors of outcome in men with localized prostate cancer. The Columbia Urologic Oncology Database was reviewed (1988-2006); 3460 had undergone RP. Patients who received neoadjuvant/adjuvant therapy or had incomplete data were excluded, yielding 1932 in the analysed sample. Analysis of variance (ANOVA) methods were used to assess differences in PSA level (on a log scale) among three different groups of patients, categorized by their Gleason sum scores, as <7, 7 and >7. To account for full penetrance of PSA screening, surgery before 1998 was considered as a potential confounder. ANOVA was used to determine whether the association of Gleason score and PSA levels differed before and after 1998. The effect of PSA level on biochemical failure was examined for variance among the three Gleason score groups using a Cox proportional hazards model with time to biochemical failure as the outcome, logPSA, Gleason sum (<7, 7 and >7), their interaction, and clinical stage as the predictors. Concordance indices (c-index) were calculated for the model with and without the interaction term between PSA and Gleason sum to determine its significance. Of 1932 patients, 1190 (61.6%) had a Gleason sum of <7, 595 (30.8%) of 7 and 146 (7.6%) of >7. The median PSA level was 5.9, 6.1 and 7.8 ng/mL, respectively (P < 0.001). After adjusting for clinical stage, there was no significant interaction effect (P = 0.34) between Gleason sum and time of surgery on PSA level, implying that the relationship between Gleason sum and PSA levels has not changed over these two periods, despite changes in PSA screening. Results from the Cox model showed that PSA level, Gleason sum, their interaction term and clinical stage were significant predictors of biochemical failure. The c-index for the model without the interaction term was 0.70 and increased to 0.72 when including it, indicating an increase in the predictive ability of the model when including the interaction term. PSA level and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure. This study shows that, for an individual patient, the higher the initial PSA level the higher the risk of having poorly differentiated prostate cancer. Also, predictive models of biochemical failure can be improved by considering the interaction between PSA and Gleason sum.

Does Transurethral Resection of Prostate (TURP) Affect Outcome in Patients Who Subsequently Develop Prostate Cancer?

Pretreatment prostate specific antigen (PSA) is a strong predictor of prostate cancer outcome after radiotherapy and is a key parameter in pretreatment risk assessment. Because PSA is secreted from both benign and malignant tissue, a prior transurethral resection of prostate (TURP) may lower pretreatment PSA levels out of proportion to the extent of cancer. The purpose of this study was to determine whether a history of TURP is associated with increased biochemical failure (BF) after definitive radiotherapy for prostate cancer. From April 1989 to October 2001, 1135 men with low to intermediate risk T1c-2NX/0M0 (2002 AJCC) prostate cancer with a pretreatment PSA less than 20 ng/mL received three-dimensional conformal radiotherapy (median dose, 76 Gy) without androgen deprivation. The median pretreatment PSA was 7.4 ng/mL (range, 0.4 to 19.9). There were 126 men with a prior history of TURP. The Cox proportional hazards model was used for univariate and multivariate analyses for BF (nadir + 2 ng/mL definition). On multivariable analysis, Gleason score (GS), PSA, and T-stage were significant predictors of BF in a model containing TURP and dose. A history of TURP was not a significant independent predictor of BF on subgroup analysis. There was a trend toward significance for the subgroup of GS less than 7 (P = 0.12). A history of prior TURP does not affect outcome after RT for prostate cancer in low to intermediate risk patients.

Complete Resection of Seminal Vesicles at Radical Prostatectomy Results in Substantial Long-Term Disease-Free Survival: Multi-institutional Study of 6740 Patients

To estimate the disease-specific survival of patients with complete removal of the seminal vesicles (SVs) at radical prostatectomy and to develop a nomogram for the prediction of SV invasion (SVI). An analysis of 6740 patients from three institutions was performed. The primary outcome was biochemical failure analyzed according to the presence or absence of SVI using the Kaplan-Meier method and Cox proportional hazards model. The variables analyzed included age, biopsy Gleason score, clinical T stage, margin status, extracapsular extension, SVI, surgical Gleason score, initial prostate-specific antigen level, and institution. Logistic regression analysis was used to determine the preoperative factors predicting for SVI and create the model for the nomogram. Of the 6740 patients, 566 (8.4%) had positive SVs. The median follow-up was 33.4 months (range 1 to 239). The 5 and 10-year biochemical relapse-free survival rate was 38.0% and 25.6%, respectively, for patients with positive SVs and 85.7% and 77.2%, respectively, for patients with negative SVs (P <0.0001). In the multivariate model, all variables, except for biopsy Gleason score and T stage, were significant predictors of biochemical failure (P <0.05), and all variables, except for age, were predictors of SVI. The nomogram achieved an area under the curve of 0.80. These results have demonstrated that a substantial number of patients with SVI are disease free at 5 and 10 years after complete excision without adjuvant therapy. These findings suggest the therapeutic efficacy of complete SV excision and can identify those with a nomogram-predicted increased risk of SVI who might benefit from complete excision.