Percentage of positive biopsy cores as predictor of clinical outcome in prostate cancer treated with radiotherapy

PURPOSE: The clinical significance of pretreatment biopsy characteristics is not well understood relative to known prognostic factors. We performed a complete pathology analysis of pretreatment biopsy specimens in an attempt to clarify their impact on clinical outcome following radiotherapy. MATERIALS AND METHODS: From 1991 to 1999, 160 patients with locally advanced prostate cancer were prospectively treated with external beam radiotherapy in combination with high dose rate brachytherapy at our hospital and had pretreatment biopsy material available for complete pathological review. Patients with pretreatment prostate specific antigen (PSA) 10.0 ng./ml. or greater, Gleason 7 or greater or clinical stage T2b-T3c N0 M0 disease were eligible for study entry. Pelvic external beam radiotherapy (46.0 Gy.) was supplemented with 3 (1991 to 1995) or 2 (1995 to 1999) ultrasound guided transperineal interstitial iridium high dose rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy. per implant. All pretreatment biopsy specimen slides from each case were reviewed by a single pathologist (N. S. G.). Median followup was 4.2 years. Biochemical failure was defined as 3 consecutive PSA increases. RESULTS: On univariate analysis pretreatment PSA, Gleason score, clinical T classification, percentage of positive biopsy cores, dose per implant and total radiotherapy dose (equivalent in 2 Gy. fractions) were significantly associated with biochemical failure. Perineural invasion was of borderline significance (p = 0.07). On univariate analysis for clinical failure only Gleason score and percent positive cores were significant. Percent positive cores was associated with biochemical and clinical failure whether analyzed in subgroups or as a continuous variable. Patients with less than 33% positive cores had a 5-year biochemical control rate of 83% and 5-year clinical failure rate of only 7%. Conversely, patients with more than 67% positive cores had a 5-year biochemical control rate of only 57% and 25% had clinical failure at 5 years. Since percent positive cores correlated with biochemical and clinical failure, an analysis was performed to determine which other prognostic factors were associated with percent positive cores. Pretreatment PSA level, Gleason score, clinical T classification and perineural invasion were significantly associated with a higher percent positive cores. Nevertheless, on Cox multiple regression analysis higher percent positive cores, pretreatment PSA and Gleason score remained independently associated with biochemical failure but not T classification. On Cox multiple regression analysis for clinical failure only Gleason score remained independently significant with percent positive cores maintaining borderline significance (p = 0.07). CONCLUSIONS: Percent positive pretreatment biopsy cores is a powerful predictor of biochemical and clinical outcome for prostate cancer treated with radiotherapy, independent of other known prognostic factors. Percent positive cores should be seriously considered as a primary factor in risk group stratification for prostate cancer.     

Treatment of intermediate-risk prostate cancer with brachytherapy without supplemental pelvic radiotherapy: a review of the H. Lee Moffitt Cancer Center experience

PURPOSE: To determine the biochemical outcomes of patients with intermediate-risk prostate cancer treated at the H. Lee Moffitt Cancer Center with an I-125 permanent seed implant without supplemental pelvic radiotherapy. METHODS AND MATERIALS: Under an institutional review board approved protocol, the charts of 88 patients with intermediate-risk prostate cancer and a minimum follow-up of 36 months treated with brachytherapy without supplemental pelvic radiotherapy were reviewed. Median follow-up for the whole cohort was 57 months (range 37-121). Biochemical failure was defined using the American Society for Therapeutic Radiology and Oncology definition. RESULTS: The 5-year biochemical failure-free survival for the cohort was 83%. Patients with perineural invasion had a worse biochemical outcome, which was statistically significant (perineural invasion vs. no perineural invasion, 5-year biochemical failure-free survival 64% vs. 89%, P = 0.004). None of the following factors were found significant in this subset of patients: Gleason scores 6 versus 7, primary Gleason grades 3 versus 4, percentage of core positive <20% versus >20%, number of cores positive <2 versus 2 versus >2, hormonal therapy versus no hormonal therapy, T1 versus T2, prostate-specific antigen <10 versus >10, or > or =2 intermediate risk factors versus 1 intermediate risk factor. CONCLUSIONS: Our data suggest that patients with intermediate-risk prostate cancer may be treated effectively with brachytherapy without supplemental pelvic radiotherapy. However, because of the limited nature of our study, we cannot exclude that patients with intermediate-risk prostate cancer may benefit from supplemental external beam radiotherapy.     

Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database

PURPOSE: Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. CONCLUSIONS: Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.     

High dose rate brachytherapy as a boost for the treatment of localized prostate cancer

PURPOSE: We report the outcome and toxicities of high dose rate brachytherapy as a boost for localized prostate cancer. MATERIALS AND METHODS: Between 1996 and 2003, 309 patients with prostate carcinoma were treated with external beam radiation therapy and high dose rate brachytherapy. Furthermore, 36% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 3 groups. Group 1 of 67 patients had Gleason score 6 or less, pretreatment prostate specific antigen 10 ng/ml or less and clinical stage T2a or less. Group 2 of 109 patients had Gleason score 7 or greater, pretreatment prostate specific antigen greater than 10 ng/ml and clinical stage T2b or greater. Group 3 of 133 patients had 2 or more of these higher risk factors. RESULTS: At a median followup of 59 months the 5-year biochemical control rate, as defined by the American Society for Therapeutic Radiation and Oncology, was 86%, cause specific survival was 98% and overall survival was 91%. Biochemical control in stratified groups 1 to 3 was 98%, 90% and 78%, respectively. On univariate analysis risk group, pretreatment prostate specific antigen and Gleason score were significant predictors of biochemical control. However, on multivariate analysis only risk group and pretreatment prostate specific antigen were significant. Using the Common Toxicity Criteria scale there were 2 cases of grade 3 acute urinary toxicity. Regarding late side effects 4% of patients had grade 3 genitourinary toxicity and 1 had a grade 4 rectal complication. CONCLUSIONS: External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent biochemical control, cause specific survival and overall survival with minimal severe acute or late complications.     

Conformal high dose rate brachytherapy improves biochemical control and cause specific survival in patients with prostate cancer and poor prognostic factors

PURPOSE: To improve outcome for patients with prostate cancer with poor prognostic factors higher than conventional radiation doses are required. To achieve this outcome a brachytherapy boost was given. We report the results of the first high dose rate dose-escalation brachytherapy trial. MATERIALS AND METHODS: Between 1991 and 2000, 207 patients were prospectively enrolled in a dose escalation trial including pelvic radiotherapy and conformal high dose rate prostate brachytherapy boost. The dose was increased from 5.5 to 11.5 Gy. per implant. Patient eligibility for the study included pretreatment prostate specific antigen 10 or greater, Gleason 7 or greater or clinical stage T2b or higher. No patient received hormonal therapy. The American Society for Therapeutic Radiology and Oncology consensus panel definition of biochemical failure was applied. RESULTS: Median patient age was 69 years. Mean followup was 4.7 years (range 0.6 to 10.4). The 5-year actuarial biochemical control rate was 74%. The 5-year biochemical control was 85% for 1 poor prognostic factor, 75% for 2 and 50% for all 3 (p = 0.001). On Cox regression multivariate analysis lower brachytherapy dose, and higher Gleason and nadir value were associated with biochemical failure. The 5-year actuarial overall survival was 92%, cause specific survival 98% and disease-free survival 68%. The 5-year actuarial rates of complications were 8% and 0% for grades 3 and 4 genitourinary, and 0.5% and 0.5% for grades 3 and 4 gastrointestinal, respectively. The 5-year actuarial impotence rate was 51%. CONCLUSIONS: For patients with poor prognostic factors external beam radiation therapy with conformal high dose rate brachytherapy boost improved biochemical control, resulting in a high cause specific survival rate with low toxicity. Another important advantage is that the patient is not radioactive after the high dose rate implant.     

The relationship between tumor volume and the number of positive cores in men undergoing multisite extended biopsy: implication for expectant management

PURPOSE: We assessed the relationship between the number of positive cores obtained at extended biopsy and tumor volume in radical prostatectomy specimens as a tool for predicting the biological significance of prostate cancer from biopsy data. MATERIALS AND METHODS: The study group included 207 men who were treated with radical prostatectomy without neoadjuvant therapy at our cancer center. All patients were diagnosed by systematic extended biopsy (10 or 11 cores) performed between 1997 and 2003. The variables analyzed were patient age, prostate specific antigen, clinical stage, biopsy Gleason score, maximum tumor length in a core, greatest percent of tumor in a core, total tumor length, total percent of tumor in all cores, positive core location, initial or repeat biopsy and prostate volume in subgroups based on the number of positive cores, that is group 1-1, group 2-2 and group 3-3 or more cores. Bivariate correlation analysis and multiple logistic regression analysis were used to determine the predictors of insignificant cancer. RESULTS: The number of positive cores was significantly related to total tumor volume (r = 0.433, p <0.001). Insignificant prostate cancer (volume less than 0.5 cc and Gleason score 6 or less) was found in 21.7% of patients (45 of 207). The incidence of insignificant cancer was 42.5% (31 of 73 patients) in group 1, 16.4% (10 of 61) in group 2 and 5.5% (4 of 73) in group 3. There was a significant difference in the incidence of insignificant cancer among the subgroups (group 1 vs 2 p <0.001, group 1 vs 3 p <0.0001 and group 2 vs 3 p <0.05). The best model for predicting insignificant cancer in group 1 was the combination of tumor length less than 2 mm, Gleason score 3 + 4 or less and prostate volume greater than 50 cc with 83.9% sensitivity (26 of 31 patients) and 61.9% specificity (26 of 42). CONCLUSIONS: The probability of insignificant cancer was directly related to the number of positive cores. Tumor length in a core, Gleason score and prostate volume significantly enhanced the prediction model for insignificant cancer in men with 1 positive core who underwent extended biopsy.     

Effect of prostate volume on tumor grade in patients undergoing radical prostatectomy in the era of extended prostatic biopsies

PURPOSE: We investigated the influence of prostate volume on biopsy and prostatectomy Gleason score, the incidence of upgrading and total tumor volume. MATERIALS AND METHODS: From 1997 to 2004, 247 patients were diagnosed with prostate cancer by multisite extended prostatic biopsy (10 or 11 cores) and underwent radical prostatectomy at our institution without neoadjuvant therapy. Medical records were reviewed to determine patient age at diagnosis, preoperative prostate specific antigen, prostate volume, clinical stage, biopsy Gleason score, pathological stage, prostatectomy Gleason score and total tumor volume. The Mann-Whitney and chi-square tests were used to compare variables among groups and multivariate regression analysis was used to determine predictors of Gleason score. RESULTS: Median patient age was 61 years and median preoperative prostate specific antigen was 5.5 ng/ml. Median prostate volume on transrectal ultrasound was 37 cc. Prostatectomy Gleason score was 6 in 31% of cases, 7 in 57% and 8-9 in 12%. Prostate volume greater than 50 cc was significantly associated with a higher incidence of well differentiated tumors (Gleason score 6) at prostatectomy, that is 17.9% in patients with a prostate volume of 25 cc or less, 28.9% in those with a prostate volume of 25 to 50 cc and 45.3% in those with a prostate volume of greater than 50 cc (p<0.01). In addition, the incidence of tumor upgrading was significantly lower in patients with a large prostate volume (greater than 50 cc) compared to that in those with a smaller prostate volume (20.8% vs 36.1%, p<0.05), particularly in the subset with biopsy Gleason score 6 (24% vs 54.1%, p<0.01). Patients with a large prostate volume (greater than 50 cc) had smaller total tumor volume with a trend toward statistical significance (median total tumor volume 0.86 vs 1.1 cc, p=0.0631). CONCLUSIONS: In the era of extended prostatic biopsies patients with a large prostate volume have a significantly higher incidence of well differentiated tumor at prostatectomy and a lower likelihood of tumor upgrading.     

Relationship between prostate cancer mortality and number of unfavourable risk factors in men treated with definitive brachytherapy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To explore whether the number of unfavourable pretreatment risk factors predicts cause‐specific mortality in men treated with prostate brachytherapy.

PATIENTS AND METHODS

Between April 1995 and March 2006, 739 patients were treated who had at least one of the following adverse risk factors: pretreatment prostate‐specific antigen (PSA) level of >10 ng/mL, a Gleason score of ≥7, clinical stage ≥T2b, or a PSA velocity (PSAV) of >2 ng/mL/year. Supplemental external beam radiotherapy (EBRT) was delivered to 464 (62.8%) men and 301 (40.7%) received androgen deprivation therapy (ADT). Of men with more than two risk factors, 87% received EBRT and 62% received ADT.

RESULTS

The biochemical progression‐free survival (bPFS), cause‐specific survival (CSS) and overall survival for all patients were 95.0%, 97.9% and 70.0% at 12 years. Men with three or four risk factors had a prostate cancer‐specific mortality (PCSM) at 12 years of 5.3%, vs 1.7% for men with one or two risk factors (P= 0.006). When ‘percentage of positive biopsy cores >50%’ replaced PSAV as a risk factor, men with two or more risk factors had a PCSM of 8.9%, vs 1.0% for men with one or two risk factors (P= 0.001). There was no difference in all‐cause mortality between the groups in either analysis.

CONCLUSION

Multimodal brachytherapy results in high rates of bPFS and CSS, even for men with several unfavourable risk factors. Men with two or more unfavourable risk factors had a slightly greater risk of PCSM and no difference in all‐cause mortality. The presence of three or four unfavourable intermediate‐risk factors does not appear to clearly identify a group that requires further treatment intensification, although the percentage of positive cores might be more predictive than PSAV.     

Tumor length and location of cancer on biopsy predict for side specific extraprostatic cancer extension

PURPOSE: We studied preoperative variables in a contemporary series of men who underwent nonnerve sparing radical prostatectomy in an effort to establish criteria that would predict side specific extraprostatic extension (EPE) of cancer. MATERIALS AND METHODS: We reviewed the records of 430 patients who underwent radical prostatectomy for localized prostate cancer with no prior therapy between 1996 and 1998, and for whom we had at least sextant biopsy information. We evaluated biopsy data (Gleason score, maximum length of cancer in positive cores, percent of cancer per involved core, proportion of positive biopsy cores, tumor location and number of positive biopsy cores) and correlated these findings with EPE at the neurovascular bundle and posterior lateral (NVB/PL) region. RESULTS: We found that a higher number of positive cores, a higher biopsy Gleason score on a side, a positive core at the basal region, 50% or greater tumor in the core or a maximum tumor length of 7 mm or greater increased the likelihood that EPE was present at the NVB/PL region on the corresponding side of the prostate. On multivariate analysis maximum tumor length 7 mm or greater and positive basal core location were the strongest independent predictors of EPE at the NVB/PL region on a given side (p <0.0001 and 0.002, respectively). CONCLUSIONS: Excluding any patient with 1 positive biopsy core with a maximum tumor length of 7 mm or greater plus a positive basal core of any tumor length and grade can decrease the risk of EPE at the NVB/PL region to approximately 10%.     

A new model using number of needles and androgen deprivation to predict chronic urinary toxicity for high or low dose rate prostate brachytherapy

PURPOSE: Prostate brachytherapy is an established treatment modality in early stage prostate cancer. We retrospectively reviewed our experience with low dose rate (LDR) and high dose rate (HDR) brachytherapy as a single treatment modality for early prostate cancer with emphasis on chronic toxicity.MATERIALS AND METHODS: From June 1996 to August 2003, 253 patients with stage II prostate cancer, prostate specific antigen less than 12 and Gleason score less than 7 were treated with brachytherapy alone at our institution. A total of 92 patients underwent HDR brachytherapy with 192Ir, while 161 underwent LDR brachytherapy with 103Pd. HDR minimum prostate dose was 38 Gy, delivered in 4 fractions with a single implant during 36 hours. For HDR we used real-time dynamic 3-dimensional ultrasound base dosimetry. For 103Pd seed implants the dose was 120 Gy using selective peripheral weighted dose distribution. Treatment was given based on patient preference after pretreatment transrectal ultrasound. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria 2.0. Median followup in all 253 cases was 2.9 years.RESULTS: In all patients the rate of 3-year urinary toxicity grade 2 or greater and grade 3 or greater was 26% and 6.9%, which was not significantly different between HDR and LDR (p = 0.3 and 0.4, respectively). However, grade 1 urogenital toxicity was lower for HDR (p = 0.002). The 3-year grade 2 rectal toxicity rate was 0.8% with no grade 3 or greater events, which was and similar in the HDR and LDR groups (1% and 0.6%, respectively). No cancer related deaths occurred and 4-year overall survival was 99% for HDR and 96.4% for LDR (p = 0.4). The 3-year American Society for Therapeutic Radiology and Oncology biochemical control rate was 90% for LDR and 93% for HDR. Cox multivariate analysis for grade 2 or greater urinary toxicity was significant for the use of 14 or greater needles (HR 6.1, p = 0.02) and hormonal therapy (HR 2.2, p = 0.02). In the absence of risk factors the 4-year grade 2 or greater urinary toxicity rate was 7% vs 65% if the 2 risk factors were present (p <0.001). Impotence crude rates were 18.3% for HDR and 41.3% for LDR (p = 0.002).CONCLUSIONS: HDR and LDR chronic urinary toxicity grade 2 or greater rates were equivalent. However, grade 1 was lower for HDR. The impotence rate was decrease by half with HDR. Neoadjuvant hormonal therapy and 14 or greater needles were significantly associated with increased chronic urinary toxicity on multivariate analysis.     

Intermediate term biochemical-free progression and local control following 125iodine brachytherapy for prostate cancer

PURPOSE: We determined the 10-year biochemical and local control results for I prostate brachytherapy in men followed a minimum of 4 years. MATERIALS AND METHODS: A total of 279 men with T1-T2 prostate cancer with a minimum followup of 4 years were implanted with I from 1990 to 1998 using the real-time technique. Patients were treated with the implant alone (215 or 72.5%) or with the implant and 6 months of hormone therapy (64 or 27.6%). Of the men 185 (66.3%) agreed to ultrasound guided biopsy (6 to 12 cores) a minimum of 2 years after implantation. All patients with increasing prostate specific antigen (PSA), evidence of local recurrence or a prior positive biopsy underwent repeat biopsy yearly until biopsy became negative or there was clear evidence of biochemical (PSA) progression. The radiation dose delivered to 90% of the gland (D90) was determined 30 days after implantation by computerized tomography based dosimetry. Biochemical failure was defined as 3 consecutive PSA increases. Survival curves were calculated by the Kaplan-Meier method. Cross tabulations were tested by Pearson chi-square analysis. The effect of multiple variables was tested by the log rank test (Cox regression). RESULTS: Median patient age was 67 years (range 42 to 82) and median followup was 6 years (range 4 to 12). Of the patients 49 (17.6%) experienced failure, for a 10-year freedom from failure (FFF) rate of 78%. Univariate analysis for 10-year FFF demonstrated that initial PSA (p = 0.001), stage (p = 0.002), risk group (p <0.001), hormone therapy (p = 0.013) and D90 (p <0.001) were significant. Multivariate analysis demonstrated that D90 (p <0.001) and risk group (p = 0.013) were the only significant variables. The RR of PSA failure was 3.0 (95% CI 2.0 to 4.4, p <0.001) and 5.6 (95% CI 3.1 to 10, p <0.001) for doses below 140 and 120 Gy, respectively. Of the 185 patients 166 (90%) had a negative post-implantation prostate biopsy. FFF was 85% vs 21% in those with a positive biopsy (p <0.001). Patients with a D90 of at least 140 Gy had a positive biopsy rate of 4.8% compared to 20.5% in those with a lower dose (p <0.001). The RR for positive biopsy at doses less than 140 and 120 Gy was 2.6 (95% CI 1.6 to 4.4, p = 0.002) and 4.3 (95% CI 2.3 to 8.1, p <0.001), respectively. CONCLUSIONS: These data demonstrate high biochemical and local control in men with T1-T2 prostate cancer treated with I brachytherapy. The delivered radiation dose and risk category are important predictors of success. Patients receiving a dose of at least 140 Gy have a 90% chance of biochemical FFF and a 95.2% likelihood of local control.     

Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer

PURPOSE: We examined the implications of underestimating Gleason score by prostate biopsy in patients with biopsy Gleason 6 prostate cancer with respect to adverse pathological findings and biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on a cohort of 531 patients with Gleason score 6 on prostate biopsy who underwent radical retropubic prostatectomy between June 1992 and January 2002. Patients were excluded if they received neoadjuvant androgen deprivation. Concordance between biopsy and radical prostatectomy Gleason score was examined. A comparison was made with respect to final radical prostatectomy specimen pathology and the risk of biochemical recurrence between cases that remained Gleason 6 and those with a final grade of 7 or greater. RESULTS: A total of 451 patients were included in the analysis. Mean followup was 55.1 months (range 12 to 123.4). Of the patients 184 (41%) had a Gleason score of 7 or greater after a review of the entire prostate, while 37 (8%) had a score of less than 6 and 230 remained with Gleason 6. Patients who were under graded were more likely to have extraprostatic extension (22% vs 4%, p <0.01), seminal vesicle invasion (9% vs 2%, p <0.01) and biochemical recurrence (10% vs 3%, p <0.01) compared to those who remained with Gleason score 6. CONCLUSIONS: Gleason grade on needle biopsy is an inexact predictor of the final grade following radical prostatectomy. Patients with biopsy Gleason score 6 who are under graded are at significantly higher risk for adverse pathological features and biochemical recurrence than patients who remain with Gleason score 6 or less on final pathology findings.     

Prostate cancer with large glands treated with 3-dimensional computerized tomography guided pararectal brachytherapy: up to 8 years of followup

PURPOSE: We report post-brachytherapy results in patients with cancer in a large prostate. MATERIALS AND METHODS: From June 1, 1994 to June 30, 2000, 331 consecutive patients with a large prostate of 50 to 180 cm.3 (median 69) were treated with 3-dimensional computerized tomography guided brachytherapy. Patient age was 42 to 90 years (median 69). Of these patients 327 were available for followup for 2 to 8 years (median 4.5). Patients were stratified according to risk profile. The high risk group had 1 or more high risk factors (prostate specific antigen [PSA] greater than 20 ng./ml., Gleason greater than 7, stage T2b, T3a or T3b) or 2 intermediate risk factors (PSA 10 to 20 ng./ml. and Gleason 7). The high risk group was further stratified into subgroups with a similar risk profile. The intermediate risk group had only 1 high risk factor (PSA 10 to 20 ng./ml. or Gleason 7). The low risk group had PSA less than 10 ng./ml., Gleason less than 7 and stage T1a, b, c or T2a. A dose of 144 Gy. with 125I or 120 Gy. with 103Pd was achieved in 90% to 100% of the target. A total of 31 patients (9%) had previously undergone transurethral resection and 198 (60%) were treated with 3 months of neoadjuvant androgen ablation. RESULTS: Biochemical disease-free survival was achieved in 90% of the 182 patients at high risk, 96% of the 52 at intermediate risk and 99% of the 93 at low risk. Seven patients (2%) required catheterization during year 1 for urinary retention, 11 (3%) required transurethral prostate resection 1 to 4 years after implantation, 3 patients (1%) had grade 1 or 2 incontinence after repeat transurethral prostate resection and 4 (1%) had grade 3 or 4 rectal complications. CONCLUSIONS: The 3-dimensional computerized tomography guided pararectal permanent implant results in a high level of biochemical control with low morbidity at 2 to 8 years in patients with prostate cancer who have a large prostate. There was less favorable biochemical control in patients with PSA greater than 20 ng./ml., Gleason 7 or greater and seminal vesicle invasion.     

Prostate brachytherapy: treatment strategies.

PURPOSE: Patients who present with localized and locally advanced prostate cancer may be candidates for prostate brachytherapy. We evaluated the treatment outcomes in a diverse group of prostate cancer patients who presented with low, moderate and high risk features. MATERIALS AND METHODS: A total of 301 patients who presented with T1 to T3 prostate cancer were treated with brachytherapy alone or combined with hormonal therapy and/or external beam irradiation. Of these patients 109 at low risk with prostate specific antigen (PSA) 10 ng./ml. or less, Gleason score 6 or less and clinical stage T2a or less were treated with 125iodine alone, 152 at moderate risk with PSA greater than 10 ng./ml., Gleason score greater than 6 or stage T2b or greater were treated with 125iodine or 103palladium or combined implant alone with 5 months of hormonal therapy, and 40 at high risk with PSA greater than 15 ng./ml., Gleason 8 or greater, clinical stage T2c to T3 or positive seminal vesicle biopsy (20) were treated with combination brachytherapy, external beam irradiation and 9 months of hormonal therapy. Patients with a positive seminal vesicle biopsy (T3c disease) and negative pelvic lymph nodes were included in the high risk group, and the walls of the seminal vesicles were also treated with implantation. Followup was performed every 6 months with digital rectal examination and ultrasound evaluation. Prostate biopsy was routinely recommended 2 years after completion of the radiation. Failure was defined as PSA increase on 2 consecutive determinations above 1 ng./ml. or evidence of local recurrence on digital rectal examination, transrectal ultrasound or biopsy. Kaplan-Meier projections were used to calculate progression-free survival rates. RESULTS: Of the 109 patients at low risk followed from 1 to 7 years (median 18 months) 91% were free of PSA failure at 4 years. No patient experienced urinary incontinence following implantation, although grade 1 to 2 radiation proctitis occurred in 5 (4.5%). Of the 152 patients at moderate risk 73 received implantation and 79 received implantation combined with hormonal therapy. The 4-year biochemical freedom from failure rate for the hormone group was 85% versus 58% for the no hormone group (p = 0.08). The difference was more significant for those with Gleason score 7 or greater (90 versus 43%, p = 0.01) and for those with PSA greater than 10 ng./ml. (87 versus 59%, p = 0.04). Grade 1 to 2 radiation proctitis occurred in 1 of the 79 patients (1.3%) receiving hormonal therapy and in 3 (4%) treated with implantation only. There were no cases of urinary incontinence. Of the 40 patients at high risk 71% were free of biochemical failure at 3 years. Of the 4 patients with failure (10%) 3 (75%) originally had positive seminal vesicle biopsies. Five patients experienced gastrointestinal complications, although none was grade 3 or 4. The actuarial freedom from grade 2 proctitis was 82%. No patient experienced urinary incontinence. Prostate biopsies were negative in 87% of the low risk, 96.8 (hormone group) versus 68.6% (no hormone group) of the moderate risk (p = 0.0023) and 86% of the high risk patients. CONCLUSIONS: Brachytherapy appears to offer comparable results to external beam irradiation and radical prostatectomy when patients are stratified by disease extent. Adopting a strategy of implant alone, implant with hormonal therapy or implant with hormonal therapy and external beam irradiation in patients who present with low to high risk features can improve the overall results in the more advanced cases.     

Differences in histopathological and biochemical outcomes in patients with low Gleason score prostate cancer

Study Type – Diagnosis (case series)
Level of Evidence 4

OBJECTIVE

To test whether the number or percentage of positive biopsy cores can be used to discriminate between patients with prostate cancer of a favourable and less favourable Gleason score (GS) ≤3 + 3, as prognostically, not all GS 3 + 3 prostate cancers are the same.

PATIENTS AND METHODS

In all, 1106 consecutive patients with a prostate‐specific antigen (PSA) level of ≤10 ng/mL and a biopsy GS of ≤3 + 3 or 3 + 4 had an open radical prostatectomy. The number of positive biopsy cores (≤2 vs ≥3) were stratified into low‐ vs high‐risk groups. Subsequently, we stratified patients according to the GS and the percentage of positive biopsy cores (<50% vs ≥50%). The pathological stage and the 5‐year biochemical recurrence (BCR)‐free survival rates were examined in univariable and multivariable models.

RESULTS

Based on the number of positive cores, the rate of extraprostatic disease was 11.7% and 23.3%, respectively, in the low‐and high‐risk GS ≤3 + 3 groups (P < 0.001). The 5‐year BCR‐free survival rates were 95.0%, 77.8%, 81.2% and 66.5% for, respectively, low‐ and high‐risk GS ≤3 + 3 and for low‐ and high‐risk GS 3 + 4 patients. Univariable and multivariable intergroup BCR rate differences were statistically significant between low‐ vs high‐risk GS 3 + 3 patients (P < 0.001), but not significant between high‐risk GS ≤3 + 3 vs low‐risk GS 3 + 4 patients (P = 0.6). Comparable results were obtained when comparisons were made according to the percentage of positive biopsy cores.

CONCLUSIONS

Our results corroborate the finding that not all patients with a biopsy GS of ≤3 + 3 prostate cancer have low‐risk disease. High‐risk GS ≤3 + 3 patients have a similar risk profile as more favourable GS 3 + 4 patients. This finding warrants consideration when deciding on treatment.     

The effect of sampling more cores on the predictive accuracy of pathological grade and tumour distribution in the prostate biopsy

OBJECTIVE: To determine if increasing the number of cores at biopsy improves the predictive accuracy of the Gleason score or aids in anticipating the location and volume of prostate tumour. PATIENTS AND METHODS: The charts of 75 consecutive patients who underwent radical retropubic prostatectomy for clinical T1-2 adenocarcinoma of the prostate were reviewed retrospectively; 31 patients had a sextant biopsy (group 1) and 44 had > or = 8 cores taken (group 2). The concordance between biopsy data and final prostatectomy Gleason score, tumour location and volume was determined for each group. RESULTS: There were no differences in mean age, prostate-specific antigen level before biopsy or biopsy Gleason score for the two groups; 58% of group 1 had their final pathological grade changed after prostatectomy, vs 29% of group 2 (P < 0.05). In neither group was there a significant correlation between the percentage of cores positive for tumour and the percentage volume of prostate involved with cancer, or the ability of the biopsy to predict tumour location. CONCLUSION: Taking > or = 8 biopsy cores improved the pathological grading accuracy, which may be valuable in choosing a treatment for the patient with newly diagnosed prostate cancer.     

The extent of biopsy involvement as an independent predictor of extraprostatic extension and surgical margin status in low risk prostate cancer: implications for treatment selection

PURPOSE: We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b). MATERIALS AND METHODS: From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins. RESULTS: Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population. CONCLUSIONS: In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.     

Does prostate biopsy Gleason score accurately express the biologic features of prostate cancer?

PURPOSE: To correlate Gleason grading in prostate biopsies with the final Gleason score in radical prostatectomy specimens, and to investigate predictors for concordance and preoperative undergrading. MATERIALS AND METHODS: The charts of 303 patients who underwent radical retropubic prostatectomy between 1992 and 2002 were retrospectively reviewed. Prostate biopsy and surgical specimen Gleason scores and correlative clinical data were recorded, and a multivariate analysis model was applied. RESULTS: Data were available in 293 cases (97%). The preoperative biopsy predicted the prostatectomy Gleason score accurately in 51% and undergraded them in 41% of the patients. Accuracy rates were significantly higher for Gleason scores 7-10 compared to low Gleason scores (2-4), concordance 90% and 6%, respectively (P < 0.01). Moreover, accuracy rates were higher in patients with prostate-specific antigen (PSA) higher than 10 ng/ml (85% vs. 40%; P < 0.01) and prostate glands smaller than 55 g (68% vs. 38%; P < 0.01). In 233 patients, the biopsy Gleason score did not include 4 or 5 components. Upgrading to 4 or 5 in 1 of the components was noted in 32 patients (14%). Multivariate analysis revealed that upgrading is associated with preoperative serum PSA (odds ratio 1.05; P < 0.05) and the percentage of positive cores in the biopsy (odds ratio 1.47; P < 0.001). CONCLUSIONS: Biopsy Gleason scores of 2-4, low PSA, and a low percentage of positive cores in the biopsy can predict the biopsy driven biologically significant undergrading of 1 of the components of the Gleason score that may adversely affect therapeutic decisions.     

Prediction of extraprostatic extension in the neurovascular bundle based on prostate needle biopsy pathology, serum prostate specific antigen and digital rectal examination

PURPOSE: There are few studies on predictors of extraprostatic extension (EPE) in the region of the neurovascular bundle (NVB). We investigated whether clinical information and prostate biopsy data could predict EPE of clinical localized prostate cancer. MATERIALS AND METHODS: Through a retrospective analysis of the pathology database we identified 2,660 cases of clinically localized prostate cancer treated with radical retropubic prostatectomy without preoperative adjuvant therapy at The Johns Hopkins Hospital. The study sample involved a total of 3,006 lobes with prostate cancer including 2,070 with organ confined disease, 620 with EPE in the NVB at the posterolateral edge of the prostate and 316 with EPE in a region other than the NVB (EPE elsewhere). Through univariate and multivariate logistic regression analysis we determined whether patient age, year of surgery, serum prostate specific antigen, digital rectal examination, biopsy highest Gleason score, perineural invasion, percent of side specific biopsy cores with cancer, percent of each core involved with cancer and the maximum percent of a core involved with cancer was predictive of EPE in the NVB. RESULTS: Prostate specific antigen (10 or greater vs less than 10), biopsy Gleason score (7 or greater vs 6 or less), digital rectal examination (abnormal vs normal), percent of side specific cores with tumor (greater than 33.3% vs 33.3% or less) and average percent involvement of each positive core (greater than 20% vs 20% or less) were all found to be statistically significant independent predictors of NVB penetration in multivariate analysis. The generated model stratifies each of these variables into high and low risk. The probability of EPE in the NVB was less than 10% in cases with 1 or fewer of the higher risk variables and was 10% or greater in cases with more than 1 of the higher risk variables. CONCLUSIONS: The model generated in this study allows for the preoperative identification of patients with 10% or greater probability of EPE in the NVB. Our algorithm will help provide objective parameters that aid in the decision to spare the NVB safely.