The influence of interpatient and intrapatient rectum variation on external beam treatment of prostate cancer.

PURPOSE: The rectal dose/volume relationship and inherent variations thereof are fundamental parameters to guide dose escalation in prostate cancer treatment. This study evaluates the effect of rectal dose/volume variation on the risk of rectal complication for different planning target volume (PTV) constructions. METHODS AND MATERIALS: Thirty prostate patients with multiple daily CT scans obtained during the treatment course were included in this retrospective study. The dose distribution was calculated based on the pretreatment CT image alone. Treatment plans were generated by applying the four-field-box beam arrangement to each of three different PTVs: PTVs with 0.5-cm and 1.0-cm uniform margins, and a patient-specific PTV constructed using treatment imaging feedback. For each of the 30 patients, the rectal wall as manifested on each of multiple CT images was delineated after image bony registration to the pretreatment CT image, and applied to the corresponding treatment plan to obtain the rectal wall dose-volume histogram (DVH). Interpatient and intrapatient rectal dose/volume variations were quantified accordingly. The corresponding uncertainty and sensitivity of the risk of rectal complication to the variations were evaluated for each of the three PTVs. Finally, the efficacy of using multiple CT images to reduce uncertainty in planning evaluation was examined. RESULTS: Sensitivity of the risk of rectal complication to rectal dose/volume variation strongly depends on the clinical target volume (CTV)-to-PTV margin or prescription dose, or both. Compared to the conventional two-dimensional (2D) prostate cancer treatment, the sensitivity for a conformal treatment can be 3 times higher or more. Due to the interpatient rectal dose/volume variation, the individual normal tissue complication probability (NTCP) was distributed from 10% to 37% when a common prescription dose was applied for all patients. The intrapatient rectal dose/volume variation introduces at least +/- 25% uncertainty in the NTCP calculation for at least 10% or 25% of the patients treated with the PTV of 1.0- or 0.5-cm margin, respectively. These uncertainties were larger for the smaller PTV, with the standard deviation up to 20%. By applying multiple CT image feedback, the NTCP uncertainty could be reduced by a factor of 2. CONCLUSIONS: Shape and position variation of rectum has less influence on treatment planning in the conventional 2D treatment of prostate cancer. However, this influence is quickly growing with high treatment dose or small CTV-to-PTV margins. To reduce the variation and uncertainties in the treatment planning evaluation associated with the inter- and intrapatient rectal dose/volume variation, the iso-NTCP model and treatment image feedback technique can be applied in dose escalation trials of prostate cancer treatment.

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.

A comparison of external beam radiation therapy versus radical prostatectomy for patients with low risk prostate carcinoma diagnosed, staged, and treated at a single institution.

BACKGROUND: The authors retrospectively reviewed their institution's long term experience treating a group of comparably staged low risk prostate carcinoma patients with either radical prostatectomy or external beam radiation therapy (RT) to determine whether the method of treatment resulted in significant differences in biochemical control and/or survival. METHODS: From January of 1987 through December of 1994, 382 patients (157 who underwent radical prostatectomy and 225 who received external beam RT) were treated with curative intent for localized prostate carcinoma at William Beaumont Hospital. All patients had a pretreatment serum prostate specific antigen (PSA) level < or =10.0 ng/mL and a biopsy Gleason score or =0.2 ng/mL at any time after prostatectomy. For RT patients, biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Pretreatment PSA levels and Gleason scores were not significantly different between patients treated with radical prostatectomy or RT. The median follow-up in each treatment group was 5.5 years. RESULTS: The 7-year actuarial rates of biochemical control and cause specific survival were not significantly different between patients treated either with radical prostatectomy or RT (67% vs. 69% for biochemical control and 99% vs. 97% for cause specific survival, respectively). A number of clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical failure (i.e., age, pretreatment PSA, Gleason score, and treatment modality). Only pretreatment PSA and Gleason score were significantly related to outcome in both univariate and multivariate analyses. CONCLUSIONS: Low risk prostate carcinoma patients with similar pretreatment PSA levels and biopsy Gleason scores treated at the same institution with either radical prostatectomy or RT achieved similar 7-year rates of biochemical control and cause specific survival, regardless of treatment technique. These findings suggest that for patients with pretreatment PSA levels

Treatment outcome with adjuvant and salvage irradiation after radical prostatectomy for prostate cancer.

OBJECTIVES: To determine the factors associated with outcome by reviewing our institution's experience treating patients with external beam radiation therapy (RT) after radical prostatectomy. METHODS: Sixty-one patients received RT to the prostatic fossa after radical prostatectomy for prostate cancer (median dose 59.4 Gy). Thirty-eight patients received adjuvant RT within 6 months of surgery for adverse pathologic findings only. Therapeutic RT was administered to 23 patients either for a persistently elevated postoperative prostate-specific antigen (PSA) level (n = 2), a rising PSA level more than 6 months after surgery (n = 9), or a biopsy-proven local recurrence (n = 12). Preoperative and preradiation PSA values, Gleason score, pathologic findings, patient age, total RT dose, and indication for RT were analyzed for their impact on biochemical control. The median follow-up was 48 months. RESULTS: Patients treated with adjuvant RT achieved 3 and 5-year biochemical control rates of 84% and 67%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. No variable was associated with 5-year outcome. The 5-year actuarial rate of biochemical control for patients treated with therapeutic RT was 16%. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. Only a pre-RT PSA level of 2 ng/mL or less was associated with an improved rate of biochemical control at 3 years (80% versus 27%, P = 0.001). However, at 5 years, this difference was not statistically significant. A separate analysis was performed to determine the prognostic factors associated with outcome for the entire group of patients. Only the indication for RT (adjuvant versus therapeutic) was associated with 5-year outcome. Patients treated with adjuvant RT had a statistically significant improvement in 5-year actuarial rates of biochemical control (67% versus 16%, P <0.001) and disease-free survival (66% versus 46%, P = 0.037) but not in overall survival. There were no statistically significant differences between patient groups with respect to age, preoperative PSA, Gleason score, pathologic T stage, median follow-up, and total RT dose. CONCLUSIONS: At our institution, patients treated with adjuvant RT after prostatectomy for adverse pathologic findings achieved excellent rates of biochemical control that were significantly better than that of similar patients treated therapeutically for persistent or rising PSA or clinical local recurrence.

Conformal high dose rate iridium-192 boost brachytherapy in locally advanced prostate cancer: superior prostate-specific antigen response compared with external beam treatment.

PURPOSE: Prostate-specific antigen levels are used to judge disease control of prostate cancer. No published data attest to the greater ability of conformal brachytherapy to control disease compared with conventional radiation at a single institution. This report compares the biochemical response rates in patients with stages T2b to T3c prostate cancer treated with conformal brachytherapy boost and external beam radiation with the rates in patients treated with conventional external radiation alone. MATERIALS AND METHODS: From November 1991 through November 1995, 58 patients received 45.6 Gy pelvic external irradiation and three high dose rate iridium-192 conformal boost implants of 5.5 to 6.5 Gy each. They were compared with 278 similarly staged patients treated from January 1987 through December 1991 with external beam radiation to prostate-only fields (median dose 66.6 Gy). No patient received androgen deprivation. Patient outcome was analyzed for biochemical control. Biochemical failure was defined as a prostate-specific antigen level > 1.5 ng/mL and rising on two consecutive values. If serial posttreatment prostate-specific antigen levels were showing a continuous downward trend, failure was not scored. RESULTS: Median follow-up was 43 months for the conventionally treated group and 26 months for the brachytherapy boost group. The median pretreatment prostate-specific antigen level was 14.3 ng/mL for the external-beam-radiation-alone group and 14.0 ng/mL for the brachytherapy boost group. The median Gleason scores were 6 and 7, respectively, for the two groups. The biochemical control rate was significantly higher in the brachytherapy boost treatment group. Three-year actuarial biochemical control rates were 85% versus 52% for the conformally and conventionally treated patients, respectively. In a multivariate analysis, the use of conformal brachytherapy boost and pretreatment prostate-specific antigen level were significant prognostic determinants of biochemical control. The 3-year actuarial rates of biochemical control for conformally versus conventionally treated patients, respectively, were 83% versus 72% for a pretreatment prostate-specific antigen level of 4.1 to 10.0 ng/mL, 85% versus 47% for a prostate-specific antigen level of 10.1 to 20.0 ng/mL, and 89% versus 29% for prostate-specific antigen > 20 ng/mL. When the analysis was limited to patients in both groups with a minimum 12-month follow-up, the brachytherapy boost group continued to show a higher biochemical control rate compared with the conventional radiation group (3-year actuarial rates of 86% vs 53%). DISCUSSION: These preliminary results show a significant improvement in the biochemical response rate with conformal boost brachytherapy and pelvic external radiation compared with conventional radiation alone. These results, coupled with our previously reported acceptable toxicity rates, support the use of this technique.

Assessing the variability of outcome for patients treated with localized prostate irradiation using different definitions of biochemical control.

PURPOSE: Biochemical control using serial posttreatment serum prostate specific antigen (PSA) levels is being increasingly used to assess treatment efficacy for localized prostate cancer. However, no standardized definition of biochemical control has been established. We reviewed our experience treating patients with localized prostate cancer and applied three different commonly used definitions of biochemical control to determine if differences in therapeutic outcome would be observed. METHODS AND MATERIALS: Between January 1987 and December 1991, 480 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. The median dose to the prostate was 66.6 Gy (range 58-70.4) using a four-field or arc technique. Pretreatment and posttreatment serum PSA levels were recorded. Over 86% (414 of 480) of patients had a pretreatment PSA level available. Three different definitions of biochemical control were used: (a) PSA nadir < 1 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (b) PSA nadir < 1.5 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (c) Posttreatment PSA nadir < 4 ng/ml without a time limit. Once the nadir was achieved, if it did not rise above normal the patient was considered to be biochemically controlled. Clinical local control was defined as no palpable prostate nodularity beyond 18 months, no new prostate nodularity, or a negative prostate biopsy. RESULTS: Median follow-up was 48 months (range 3-112). Pretreatment PSA values were correlated with treatment outcome using the three definitions of biochemical control as well as clinical local control. Pretreatment PSA values were stratified into five groups (Group 1: PSA < 4; Group 2: PSA 4-10; Group 3: PSA 10-15; Group 4: PSA 15-20; and Group 5: PSA > 20), and 5-year actuarial rates of biochemical control were calculated using the three biochemical control and one clinical local control definitions. For Group 1, 5-year actuarial rates of biochemical control were 84%, 90%, 91%, and 96% for Definitions 1-3 and clinical local control, respectively. For Group 2, 5-year actuarial control rates were 45%, 54%, 74%, and 92% for the four definitions, respectively. For Group 3, 5-year actuarial control rates were 26%, 31%, 63%, and 100% for the four definitions, respectively. For Group 4, 5-year actuarial control rates were 24%, 24%, 50%, and 100% for the four definitions, respectively. Finally, for Group 5, 5-year actuarial control rates were 5%, 14%, 15%, and 89% for the four definitions, respectively. Depending on the definition used, statistically significant differences overall in outcome rates were observed. Differences between all four definitions for all pairwise comparisons ranged from 5 to 53% (p < 0.001). CONCLUSION: When different definitions of biochemical control are used in assessing treatment outcome, significantly different rates of success are noted. Until a standardized definition of biochemical control is adopted, differences in treatment outcome cannot be meaningfully compared.