Positive Post-treatment Biopsy Research Articles

PD15-03 RADIATION DOSE REQUIRED TO CONTROL PROSTATE CANCER AS DETERMINED BY POST-TREATMENT BIOPSY: LONG TERM RESULTS

You have accessJournal of UrologyCME1 Apr 2023PD15-03 RADIATION DOSE REQUIRED TO CONTROL PROSTATE CANCER AS DETERMINED BY POST-TREATMENT BIOPSY: LONG TERM RESULTS Nelson Stone, Rendi Shue, Barry Rosenstein, and Richard Stock Nelson StoneNelson Stone More articles by this author , Rendi ShueRendi Shue More articles by this author , Barry RosensteinBarry Rosenstein More articles by this author , and Richard StockRichard Stock More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003262.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiation therapy for prostate cancer is typically prescribed at a standard dose, 79-81 Gy for external beam irradiation (EBRT) and 145 Gy for iodine-125 brachytherapy (BT). Unlike prostatectomy where the gland is removed at the time of treatment successful radiation treatment relies on the death of all cancer cells in situ. However, the dose requirement for different Gleason grade groups or NCCN risk groups may also differ. We investigated the relationship between the biological effective dose (BED) and local control as determined by post-treatment biopsy (PB) in a large cohort of men who had BT +EBRT. METHODS: 545 men who had BT were followed a median of 11 years (range 2-26) and had PB a mean of 3.2 years (2-17) post-treatment. All PB were performed by one investigator (NNS) and routinely performed at 2 years or later for a rising PSA. Median age, PSA and BED were 66 years (41-85), 7.0 ng/ml (1-189) and 185.5 Gy (15-282). 295 (54.1%) received hormone therapy (HT) for a median of 6 months. Radiation doses were converted post-implant to the BED using an ꭤ/β of 2. Associations with grade, stage, PSA, NCCN status, HT use, BED were compared to the PB results and prostate cancer survival (PCS) using ANOVA, chi-square, linear regression, Kaplan Meier estimates with comparisons by log rank and Cox proportion hazards. RESULTS: 34 (6.2%) of the 545 men had a positive PB which occurred a mean of 5.9 years (range 2-17) after all treatment. BED (p<0.001), stage (p=0.004), PSA (p=0.038) and HT use (p=0.019) were associated with a positive PB but only BED (p<0.001) remained significant on regression analysis. Dichotomizing BED to <140, 160, 180, 200, 220 or greater yielded optimal local control (positive biopsy rate 2% or less) at 180 Gy for all 3 NCCN risk groups (Table). Men with a positive PB had a mean BED of 136.8 vs. 181.3 Gy for negative PB (p<0.001). At <180 Gy 24/229 (10.5%) had local failure compared to 5/392 (1.7%) for higher doses (p<0.001, OR 6.7, 95% CI 2.5-17.9). PCS at 15 and 20 years for negative PB was 94.5 and 94.5% vs. 74.4 and 46.5% for a positive one (p<0.001). PCS was associated with BED (p<0.001), PSA (p=0.028) and stage (p=0.018). CONCLUSIONS: This long-term investigation defined the radiation dose necessary to eradicate prostate cancer and should be considered as the minimal requirement when prescribing and delivering this treatment option. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e419 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nelson Stone More articles by this author Rendi Shue More articles by this author Barry Rosenstein More articles by this author Richard Stock More articles by this author Expand All Advertisement PDF downloadLoading ...

Superior Post-Treatment Biopsy Outcomes with High Dose SBRT Compared to High-Dose Conventionally Fractionated IMRT for Clinically Localized Prostate Cancer

<h3>Purpose/Objective(s)</h3> To compare post-treatment biopsy outcomes for clinically localized prostate cancer patients treated with high-dose conventionally fractionated intensity modulated radiotherapy (CF- IMRT) versus high-dose stereotactic body radiotherapy (SBRT). <h3>Materials/Methods</h3> 451 patients with low and intermediate risk prostate cancer treated with high dose external beam radiotherapy underwent a post-treatment biopsy which was routinely performed at our institution to assess local control status. Biopsies were performed 2-3 years after completion of radiotherapy. 221 patients were treated with CF-IMRT to a median dose of 75.6 Gy (range: 64.8-86.4) and 230 patients were treated with SBRT to a median dose of 40 Gy in 5 fractions (range: 32.5-42.0). A 6-month course of androgen deprivation therapy (ADT) was used in conjunction CF-IMRT and SBRT in 38% and 17% of patients. The percentage comprising low, favorable intermediate and unfavorable intermediate risk group were similar (CF-IMRT: 23%, 36% and 41%; SBRT: 18%, 49%, 33%). The histological outcome of the prostate biopsy was classified as positive (prostatic adenocarcinoma without typical radiation–induced changes), negative (no evidence of carcinoma) or severe treatment effect. <h3>Results</h3> The incidence of a positive post treatment among the IMRT and SBRT cohorts were 49% and 17%, respectively (p< 0.001). The incidence of a positive biopsy for low risk, favorable- intermediate risk and unfavorable- intermediate risk patients treated with IMRT and SBRT were: IMRT: 40%, 52%, and 52%; SBRT: 7.1%, 17%, and 21%, respectively. Multivariable analysis evaluating co-variates associated with a positive post-treatment biopsy was IMRT (P< 0.001 CI:0.12, 0.33) with 5-fold higher odds of a positive biopsy compared to SBRT. Other variables including the use of ADT and the risk group did not significantly impact on the biopsy outcome. <h3>Conclusion</h3> The use of SBRT in the treatment of low and intermediate risk prostate was associated with improved post-treatment biopsy outcomes compared to conventionally fractionated IMRT. These findings were observed even in the setting of high-dose IMRT to prescribed doses of ≥75.6 Gy. We hypothesize that these findings may be related to the greater ablative potential of high dose SBRT compared to IMRT.

Predictors for post-treatment biopsy outcomes after prostate stereotactic body radiotherapy

PurposeTo investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. Materials and methods257 patients treated with prostate SBRT to dose levels of 32.5 Gy to >40 Gy in 5–6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n = 187) and the remaining 17% (n = 43) and 10% (n = 27) had low-risk and high-risk disease, respectively. ResultsThe incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n = 9/24), 21.4% (n = 6/28), 19.4% (n = 6/31), and 10.9% (n = 19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and >40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29–77% compared to negative biopsy: 7%, 95% CI: 3–14%; p < 0.001). ConclusionBased on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35–37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients.

Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer.

To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT). Retrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24-36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26-267). Sixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8-8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7-2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6-9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26-12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33-3.79). A positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.

Long-Term Implications of a Positive Posttreatment Biopsy in Patients Treated with External Beam Radiotherapy for Clinically Localized Prostate Cancer.

We determined the prognostic importance of a positive posttreatment biopsy after prostate radiotherapy. A total of 382 patients underwent a posttreatment biopsy after external beam radiotherapy for clinically localized prostate cancer. Posttreatment biopsies were classified as positive (prostatic adenocarcinoma without typical radiation induced changes), negative (no evidence of carcinoma) or adenocarcinoma with a severe treatment effect. Median followup in survivors was 9 years. Competing risks regression was used to assess relationships between prognostic predictors and cause specific mortality, distant metastasis and prostate specific antigen failure. The prevalence of positive biopsy, treatment effect and negative biopsy was 30%, 22% and 48%, respectively. Androgen deprivation therapy omission and high risk disease were associated with a 2.6 and 1.8-fold increase, respectively, in the odds of positive posttreatment biopsy. The 15-year PSA relapse rate associated with negative, severe treatment effect and positive posttreatment biopsies was 34%, 36% and 79%, respectively (p <0.001). After controlling for known predictors the risk of distant metastasis was 2.6-fold higher in patients with a positive biopsy (p <0.001) and cause specific mortality was twice as high in patients with a positive biopsy compared to those with negative and severe treatment effect biopsy outcomes (HR 2.00, p = 0.022). A positive posttreatment biopsy after external beam radiotherapy was associated with a higher risk of distant metastasis and prostate cancer related death. Patients with severe treatment effect classified biopsies have biological characteristics more like patients with a negative biopsy than a positive biopsy. Posttreatment biopsies were more often positive in the setting of external beam radiotherapy alone without androgen deprivation therapy or in the presence of high risk disease.

Five-Year Outcomes of a Phase 1 Dose-Escalation Study Using Stereotactic Body Radiosurgery for Patients With Low-Risk and Intermediate-Risk Prostate Cancer

To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer. A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5Gy in 5 fractions, and doses were then sequentially escalated to 35Gy, 37.5Gy, and 40Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60cm3. Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5years, respectively. The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P=.013). SBRT doses ranging from 32.5 to 40Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses.

Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to other prostate regions sampled

Background and purposeProstate biopsy positivity after radiotherapy (RT) is a significant determinant of eventual biochemical failure. We mapped pre- and post-treatment tumor locations to determine if residual disease is location-dependent. Materials and methodsThere were 303 patients treated on a randomized hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT. Biopsy cores were mapped to a sextant template, and 86 patients with both pre-/post-treatment systematic sextant biopsies were analyzed. ResultsThe pretreatment distribution of positive biopsy cores was not significantly related to prostate region (base, mid, apex; p=0.723). Whereas all regions post-RT had reduced positive biopsies, the base was reduced to the greatest degree and the apex the least (p=0.045). In 38 patients who had a positive post-treatment biopsy, there was change in the rate of apical positivity before and after treatment (76 vs. 71%; p=0.774), while significant reductions were seen in the mid and base. ConclusionIn our experience, persistence of prostate tumor cells after RT increases going from the base to apex. MRI was used in planning and image guidance was performed daily during treatment, so geographic miss of the apex is unlikely. Nonetheless, the pattern observed suggests that attention to apex dosimetry is a priority.

Primary Cryosurgery for Clinically Localized Prostate Cancer – Do Perioperative Tumor Characteristics Correlate With Post-treatment Biopsy Results?

To investigate the rate and predictive factors of positive post-treatment biopsy in men treated with primary cryosurgery for localized prostate cancer. A retrospective review was performed of all patients treated with primary cryosurgery at a single institution between 1999 and 2012. Perioperative prostate-specific antigen (PSA) levels, Gleason score, and number of positive preoperative biopsy cores were obtained and correlated with postoperative biopsy results. Patients were stratified according to the risk classification system of D'Amico to low-, intermediate-, or high-risk groups. Sixty-five men were treated with primary cryosurgery, and 57 of 65 (88%) of them underwent postoperative biopsy on average 9 months after the treatment. Eleven of 57 patients (19%) were found to have persistent tumor on post-treatment biopsy. Men who had positive biopsy had significantly higher perioperative PSA levels than men who had negative biopsy (preoperative PSA 12.5 vs 6.2, P = .002; post-operative PSA nadir 4.3 vs 0.71, P = .005); however, no independent predictor was found on a multivariate analysis. Gleason score and number of positive preoperative biopsy cores did not predict tumor persistence. Positive biopsy results were found more often in the intermediate- and high-risk patients, although this was not statistically significant (low risk 9%, intermediate risk 20%, and high risk 27%). Perioperative PSA levels, Gleason score, or number of positive pretreatment biopsy cores do not predict failure after primary cryosurgery for clinically localized prostate cancer. Our findings suggest that physicians, who offer primary cryosurgery to patients with localized prostate cancer, should consider offering post-treatment biopsy to patients to assure adequate cancer control.

Distant and local recurrence in patients with biochemical failure after prostate brachytherapy

Purpose To analyze the patterns of failure after the brachytherapy management of localized prostate cancer. Methods and materials From 1990 to 2008, 2869 patients underwent prostate brachytherapy and 213 experienced a prostate-specific antigen (PSA) failure by the Phoenix definition. Of these 213 patients, 33.5% were low, 18.5% intermediate, and 58% high risk. Results Of the 119 patients biopsied, 36 (30%) had a least one positive posttreatment biopsy. In univariate and multivariate analyses, PSA doubling time was the most predictive of a positive biopsy. Patients with doubling times ≤3, >3–6, ≥6–10, and >10 months had positive biopsy rates of 9%, 18%, 36%, and 42%, respectively ( p = 0.01). The actuarial rate of remaining free from distant metastases at 10 years was 73%. Patients with PSA doubling times of ≤3, >3–6, >6–10, and >10 months had freedom from distant metastases rates of 0%, 74%, 78%, and 94.5% at 10 years, respectively ( p < 0.0001). In multivariate analysis, PSA doubling time and time to PSA failure were the most significant predictors of developing distant metastases. Conclusions About one third of patients harbor a component of local failure and one fourth demonstrate clinical metastases. PSA doubling time can be used to help predict the source of a rising PSA.

Influence of Local Tumor Control on Distant Metastases and Cancer Related Mortality After External Beam Radiotherapy for Prostate Cancer

We report local control outcomes, as assessed by posttreatment biopsies in patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer. In addition, we report the influence of local tumor control on long-term distant metastases and cause specific survival outcomes. Posttreatment prostate biopsies were performed in 339 patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer. The histological outcome of prostate biopsy was classified as positive-prostatic adenocarcinoma without typical radiation induced changes or negative-no evidence of carcinoma or severe treatment effect. Median followup in this group of 339 patients was 10 years after the completion of treatment and 6.25 years after posttreatment biopsy. Overall biopsy outcomes in these patients were positive in 32%, severe treatment effect in 21% and negative in 47%. A higher radiation dose in the intermediate and high risk subgroups was associated with a lower incidence of positive biopsy. Of patients at intermediate risk who received a dose of 75.6 or greater 24% had a positive biopsy compared to 42% who received 70.2 Gy or less (p = 0.03). In the high risk group positive treatment biopsies were noted in 51% of patients who received 70.2 Gy or less, 33% of those who received 75.6 Gy and 15% of those who received 81 Gy or greater (70.2 or less vs 75.6 Gy p = 0.07 and 75.6 vs 81 Gy or greater p = 0.05). Short course neoadjuvant androgen deprivation therapy before 3-dimensional conformal radiotherapy had a significant impact on the posttreatment biopsy outcome. Of patients who did not receive androgen deprivation therapy 42% had a positive biopsy compared to 16% who received androgen deprivation therapy (p <0.0001). Patients with negative and severe treatment effect biopsies had similar 10-year prostate specific antigen relapse-free survival outcomes that were markedly different from outcomes in those with positive treatment biopsies. Multivariate analysis indicated that the strongest predictor of biochemical failure was posttreatment biopsy status (positive vs severe treatment effect or negative p <0.001), followed by pretreatment prostate specific antigen (p = 0.05) and clinical T stage (p = 0.09). Similarly multivariate analysis revealed that a positive posttreatment biopsy was one of the strongest predictors of distant metastasis and prostate cancer death in this cohort of patients. As assessed by posttreatment prostate biopsies, local control is improved with higher radiation doses. Long-term biochemical outcomes in patients with posttreatment biopsies demonstrating severe treatment effect changes were not different than those in patients with negative biopsies. We also noted that local tumor control was associated with a decrease in distant metastases and prostate cancer mortality, further highlighting the importance of achieving optimal tumor control in patients with clinically localized disease.

Phase I Trial of Replication-competent Adenovirus-mediated Suicide Gene Therapy Combined with IMRT for Prostate Cancer

Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment in which an oncolytic adenovirus armed with chemo-radiosensitizing genes is used to destroy tumor cells. Previously, we evaluated the toxicity and efficacy of this approach in two clinical trials of prostate cancer using a first-generation adenovirus. Here, we report the toxicity and preliminary efficacy of this approach in combination with intensity-modulated radiotherapy (IMRT) in patients with newly diagnosed prostate cancer using an improved, second-generation adenovirus. The investigational therapy was associated with low toxicity, and there were no dose-limiting toxicities or treatment-related serious adverse events. Relative to a previous trial using a first-generation adenovirus, there was no increase in hematologic, hepatic, gastrointestinal (GI), or genitourinary (GU) toxicities. Post-treatment prostate biopsies yielded provocative preliminary results. When the results of two similar trials were combined, 22% of evaluable patients were positive for adenocarcinoma at their last biopsy, which is better than expected (>or=40%) for this cohort of patients (P=0.038). When the results were categorized by prognostic risk, most of the treatment effect was observed in the intermediate-risk group, with 0 of 12 patients (0%) being positive for cancer at their last biopsy (P<0.01). These results further demonstrate the safety of this investigational approach and raise the possibility that it may have the potential to improve the outcome of conformal radiotherapy in select patient groups.

Prostatic Biopsy after Radiotherapy: When and How

Objectives: External beam radiotherapy and seed implantation are treatment options for clinically localized prostate cancer. Post-radiation biopsies may assess the efficacy of radiation in locally eradicating prostate cancer cells. Aim of this overview was to analyze the role of prostate rebiopsies after radiation to evaluate treatment success. Methods: A Medline search was performed from 1980 to 2001 for articles in English. Results: Based on the available data a positive prostate rebiopsy can be found in 18–90% for patients with stage T1–T3. Pretreatment PSA, pretreatment Gleason score, clinical stage and digital rectal examination (DRE) after radiotherapy correlate with biopsy results. A positive post-treatment biopsy is associated with a higher nadir PSA serum level and a higher rate of local recurrence compared to patients with negative biopsies. However, systematic prostate biopsies after radiation therapy are not necessary in the standard follow-up because a rising PSA after radiation therapy is a more rigorous end-point for evaluation of treatment efficacy. However, patients with rising PSA after irradiation without evidence of systematic disease and positive prostate biopsies may be candidates for salvage treatment. Conclusions: Prostate biopsies after radiation therapy are not necessary as a standard procedure for follow-up. Prostate rebiopsies may be an important research tool to evaluate histological changes within the prostate and may indicate local recurrence.

Importance of post-implant dosimetry in permanent prostate brachytherapy.

Post-implant dosimetry has become the gold standard for implant evaluation and it is recommended that it be performed on all patients undergoing prostate brachytherapy. The technique, results and correlation with clinical outcomes will be presented. The method and outcomes of post-implant dosimetry are explored by outlining the experience at the Mount Sinai Medical Center, New York, as well as reviewing the literature. The most accurate time to perform post-implant dosimetry is 1 month after implant. Computed tomography (CT)-based dosimetry is currently the best available technique for performing this analysis. The technique involves taking 3-mm abutting CT slices throughout the implanted area. The prostate and normal structures are outline on the CT slices. These structures are recreated in three dimensions. Dose volume histograms (DVH) are created and allow the dose to these organs to be quantified. The relationship between dosimetric findings and clinical outcomes has been established. The dose delivered to 90% of the prostate on DVH (D90) has been correlated to prostate-specific antigen (PCA) control and post-treatment biopsy results. D90 values of >or=140Gy have been associated with improved biochemical control and lower positive post-treatment biopsy results. Doses derived from the dosimetric analysis to prostate, urethra and rectum have been correlated with the development of acute and chronic urinary morbidity, sexual potency and rectal morbidity. Future initiatives involve performing dosimetric calculations intraoperatively at the time of the implant. Post-implant CT-based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe an effective treatment for prostate cancer.

Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy.

Our objective was to identify clinical pretreatment factors associated with early treatment failure after salvage cryotherapy. Between 1992 and 1995, 145 patients underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Treatment failure was defined as an increasing postcryotherapy serial prostate-specific antigen (PSA) level of more than or equal to 2 ng/mL above the postcryotherapy nadir or as a positive posttreatment biopsy. We evaluated the following factors as predictors of treatment failure: tumor stage and grade at initial diagnosis, type of prior therapy, stage and grade of locally recurrent tumor, number of positive biopsy cores at recurrence, and precryotherapy PSA level. Among patients with a prior history of radiation therapy only, the 2-year actuarial disease-free survival (DFS) rates were 74% for patients with a precryotherapy PSA less than 10 ng/mL and 28% for patients with a precryotherapy PSA more than 10 ng/mL, P <.00001. The DFS rates were 58% for patients with a Gleason score of less than or equal to 8 recurrence and 29% for patients with a Gleason score greater than or equal to 9 recurrence, P <.004. Among patients with a precryotherapy PSA less than 10 ng/mL, DFS rates were 74% for patients with a prior history of radiation therapy only and 19% for patients with a history of prior hormonal therapy plus radiation therapy, P <.002. Patients failing initial radiation therapy with a PSA more than 10 ng/mL and Gleason score of the recurrent cancer more than or equal to 9 are unlikely to be successfully salvaged. Patients failing initial hormonal therapy and radiation therapy are less likely to be successfully salvaged than patients failing radiation therapy only.

The Importance of Local Control in the Treatment of Prostatic Cancer

In a retrospective analysis of 946 patients with prostatic carcinoma treated with external beam radiotherapy between 1958 and 1989 at Stanford University Hospital the 15-year actuarial clinical local control rate was 77.8 ± 3.3% for Stanford stage T1, 61.3 ± 4.4% for stage T2 and 64.9 ± 4.8% for stage T3 disease. Overall, there was improvement in disease-specific survival without a significant alteration in survival in patients who achieved clinical local control. For the 50 Stanford stage T1 cases with local control on clinical examination and a positive post-treatment biopsy a decrease in disease-specific survival was observed. There was no difference in disease-specific survival for comparable stage T2 or T3 cases. In an analysis of patients who underwent ultrasound guided prostatic biopsy performed after irradiation the trend of prostate specific antigen was more important than biopsy results in predicting which patients would have relapse.

The clinical significance of a positive post-irradiation prostatic biopsy without metastases

To define the prognostic value of a post-irradiation prostatic biopsy, the outcome of 203 previously irradiated patients who underwent post-treatment biopsy was analyzed. The majority of patients were selected for biopsy based on an abnormal digital rectal exam or elevated prostate specific antigen. Patients with distant metastases found at the time of biopsy were excluded from further analysis. One hundred thirty-nine (139) of these had a positive biopsy and 64 were negative. Those with a positive biopsy tended to present with more locally-advanced (Stage B2/C) tumors (61%) compared to those with negative biopsies (42%). The 10- and 15-year survival and cause-specific survival from the time of initial presentation were similar for both groups. However, those with a negative biopsy had a more favorable survival and cause-specific survival from the time of post-treatment biopsy and were less likely to develop distant metastases than the positive biopsy group. These data suggest that a positive prostatic biopsy is associated with a greater likelihood of subsequent distant relapse and decreased survival following biopsy relative to patients with negative biopsies. Since a positive post-treatment biopsy is more likely among patients presenting with locally-advanced disease, perhaps more aggressive initial therapy (i.e., interstitial boost or hyperthermia) would benefit this subgroup.