Relationship of margin status and radiation dose to recurrence in post-operative vulvar carcinoma.

OBJECTIVE: To evaluate the effect of margin status and radiation dose in patients treated with radiation therapy (RT) for vulvar cancer. Clinical outcomes included vulvar recurrence (VR), relapse-free survival (RFS) and overall survival (OS). METHODS: We retrospectively reviewed the records of 300 patients with Stage I-IVA vulvar cancer treated between 1988 and 2009. Slides were reviewed and margin status was scored as negative (≥ 1 cm), close (<1cm) or positive after formalin fixation. Cox proportional hazards models were constructed to determine significant prognostic factors for vulvar relapse. RESULTS: Of 205 eligible patients, 69 (34%) had negative surgical margins, 116 (56%) had close margins and 20 (10%) had positive margins. Median follow-up time was 49 months. The 4-year RFS rate was 53% and OS was 73%. Of 78 recurrences, 62 had the vulva as the first site of recurrence. The 4-year rates of freedom from vulvar recurrence were 82%, 63% and 37% for those with negative, close and positive margins, respectively (p for trend=0.005). On multivariate analysis, close margins (HR=3.03, 95% CI 1.46-6.26) and positive margins (HR=7.02, 95% CI 2.66-18.54) were associated with a significantly increased risk of vulvar relapse. Those who received a dose ≥ 56 Gy had a lower risk of relapse than those who received ≤ 50.4 Gy (p<0.05). Though recurrences were noted with margins up to 9 mm, the highest risk of vulvar recurrence was associated with margins ≤ 5 mm (p=0.002). CONCLUSIONS: Close or positive margins were associated with a significantly increased risk of vulvar recurrence. Radiation with a dose ≥ 56 Gy may decrease the risk of vulvar recurrence.

Outcomes after radiation therapy with concurrent weekly platinum-based chemotherapy or every-3-4-week 5-fluorouracil-containing regimens for squamous cell carcinoma of the vulva.

OBJECTIVE: To compare outcomes in patients with squamous cell carcinoma (SCC) of the vulva treated with radiation (RT) and concurrent weekly platinum-based or every-3-4-week regimens containing 5-fluorouracil (5-FU). METHODS: Records of 44 patients with vulvar SCC treated with concurrent chemotherapy and radiation (chemoRT) from 1988 to 2008 were reviewed. Rates of disease-free survival (DFS), overall survival (OS), locoregional recurrence (LRR), and distant metastases (DM) were estimated using the Kaplan-Meier method. RESULTS: The median age was 63 years (range, 44-90), 84.1% of patients had ECOG performance status 0-1, and patients had FIGO Stage II (n=6), III (n=31), or IVA (n=7) disease. Patients were treated preoperatively (n=10), postoperatively (n=10), or without surgery (n=24). The median RT dose to the vulva was 50.2 Gray (range, 22-75). Concurrent chemotherapy regimens included weekly platinum (n=16) or every 3-4 week regimens with 5-FU as the backbone (n=28). With a median follow-up of 31.5 months, there was no significant difference in 2-year OS (74.5% vs. 70.0%; p=0.65), DFS (61.9% vs. 56.0%; p=0.85), LRR (31.3% vs. 32.9%; p=0.93), or DM (6.3% vs. 10.6%; p=0.81) between the weekly platinum and every-3-4-week 5-FU regimens. Twenty patients (45.4%) recurred: 16 LRR, 2 DM, and 2 with both. The clinical and pathologic complete response rates were 58.8% (20/34), and 53.8% (14/26), respectively. There was a higher proportion of grade 3 or higher acute non-skin toxicities in patients receiving every-3-4-week 5-FU (46.1% vs. 13.3%; p=0.07), but more grade 3 or higher skin toxicity in patients receiving weekly platinum (62.5% vs. 32.0%; p=0.01). CONCLUSION: OS, response rates, and recurrence rates were not significantly different after RT with concurrent weekly platinum-based versus every-3-4-week regimens containing 5-FU for vulvar SCC.

Defining the rectal dose constraint for permanent radioactive seed implantation of the prostate.

PURPOSE: This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. METHODS AND MATERIALS: Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. RESULTS: There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. CONCLUSIONS: Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer.

PURPOSE: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT). METHODS AND MATERIALS: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. RESULTS: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p=0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p=0.0008). CONCLUSIONS: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.

Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer.

PURPOSE: Identifying pretreatment and posttreatment predictors of time to prostate cancer-specific death (PCSD) after external-beam radiation therapy (RT) was the subject of this study. PATIENTS AND METHODS: A Cox regression analysis was used to evaluate the ability of the pretreatment risk group to predict time to PCSD for 381 patients who underwent RT for clinically localized prostate cancer. Posttreatment factors analyzed for the 94 patients who experienced prostate-specific antigen (PSA) failure included the time to PSA failure, the posttreatment PSA doubling time (DT), and the timing of salvage hormonal therapy. RESULTS: Despite the median age of 73 years at diagnosis, 45% of patients with high-risk disease were estimated to die from prostate cancer within 10 years after RT compared with 0% (P =.004) and 6% (P =.05) for patients with low- or intermediate-risk disease, respectively. Predictors of time to PCSD after PSA failure included PSA DT (P =.01) and delayed use of hormonal therapy (P

Effect of breast magnetic resonance imaging on the clinical management of women with early-stage breast carcinoma.

PURPOSE: To determine the impact of breast magnetic resonance imaging (MRI) on the clinical management of patients with early-stage breast cancer. PATIENTS AND METHODS: A review was performed of the records of 207 women with early-stage breast cancer (including five women with bilateral disease) who underwent breast MRI during work-up for breast conservation treatment. All patients presented with clinical stage 0, I, or II disease. For each patient, a determination was made whether the breast MRI affected the clinical management, and if so, whether the patient was well served by the change in management. RESULTS: The MRI findings affected the clinical management in 43 cases (20% of 212 breast cancers). Based on the pathology findings and the overall clinical course for each case, the breast MRI was judged to have had a strongly favorable effect on management in 18 cases (8%), a somewhat favorable effect in six cases (3%), an uncertain effect in five cases (2%), a somewhat unfavorable effect in 11 cases (5%), and a strongly unfavorable effect in three cases (1%). The effect of MRI was not significantly different for invasive carcinoma compared with ductal carcinoma-in-situ (all P > or =.27). However, the effect of MRI was significantly greater when the MRI was performed before an excisional biopsy (P =.0011) or for larger tumors (P =.0089). CONCLUSIONS: Breast MRI alters the clinical management for a sizable fraction of women with early-stage breast cancer and appears to offer clinically useful information for determining optimal local treatment.

PSA outcome following radical prostatectomy for patients with localized prostate cancer stratified by prostatectomy findings and the preoperative PSA level.

PURPOSE: Algorithms have been developed to predict time to biochemical failure (BF) following radical prostatectomy (RP) for patients with clinically localized prostate cancer. The purpose of this study was to validate an algorithm based on prostatectomy findings and to evaluate whether the preoperative serum prostate specific antigen (PSA) enhances the predictive ability of the algorithm. MATERIALS AND METHODS: Between 1988 and 2002, 2417 patients underwent RP for clinically localized prostate cancer at one of 2 large university hospitals. Patients were retrospectively stratified into 4 risk groups based upon prostatectomy grade, stage, and margin status, and were then dichotomized by the preoperative PSA level (cut point 10 ng/mL). Cox regression multivariable analyses were performed to evaluate the ability of the risk group and preoperative PSA level to predict time to BF (PSA more than 0.2 ng/mL) following RP. RESULTS: The preoperative PSA level (P < 0.0001) and risk group (P < 0.0001) were significant predictors of time to BF following RP. Estimates of the BF rates 7 years following RP were 13%, 30%, 51%, and 72% for groups 1-4, respectively (pairwise P values

Ten-year outcome after combined modality therapy for inflammatory breast cancer.

PURPOSE: To evaluate the long-term outcome of combined modality therapy for inflammatory breast cancer. METHODS AND MATERIALS: The data from 54 women treated between 1983 and 1996 for inflammatory breast cancer were analyzed. Patients with metastatic disease or disease progression on induction chemotherapy were excluded. Induction chemotherapy was given to 52 patients. Mastectomy was performed in 52 patients. Radiotherapy was delivered to the breast or chest wall and regional lymph nodes in all patients. The median follow-up for all patients was 5.1 years. RESULTS: The 5- and 10-year overall survival rate was 56% and 35%, respectively; the corresponding relapse-free survival rates were 49% and 34%. Patients with a pathologic complete response after chemotherapy with or without preoperative radiotherapy had better 5- and 10-year overall survival rates (65% and 46%, respectively) and 5- and 10-year relapse-free survival rates (59% and 50%, respectively) compared with patients without a pathologic complete response. Those patients had a 5- and 10-year relapse-free survival rate of 45% and 27%, respectively. Locoregional failure at 5 and 10 years was 8% and 19%, respectively. CONCLUSION: The outcomes for patients completing multimodality therapy compare favorably with published data; however, the exclusion of patients with progression during induction chemotherapy may account in part for these results. The pathologic complete response rate was found to be an important prognostic factor. Selected patients with inflammatory breast cancer have the potential for long-term survival.

Fifteen-year results of breast-conserving surgery and definitive irradiation for Stage I and II breast carcinoma: the University of Pennsylvania experience.

PURPOSE: To determine the 15-year outcomes for women with early stage breast cancer after breast conservation therapy. METHODS AND MATERIALS: Between 1977 and 1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18% T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and definitive irradiation. The median patient age was 52 years. Of the 937 patients, 375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249 (92%) of the 270 women with pathologically positive nodes. The median follow-up was 10.1 years. RESULTS: For the overall group, the 15-year overall survival rate was 71%, and the rate of freedom from distant metastases was 76%. The 15-year local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%. The most common first events were distant failure (13%), local failure (10%), contralateral breast cancer (7%), and second malignant neoplasms (6%). The local failure rate at 10 years for favorable subsets of tumors characterized by mammographic detection, resection with negative margins, treatment with chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively. Local failures were most commonly observed within (true recurrence), or just outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%, respectively. CONCLUSION: These high rates of survival and local control confirm that breast conservation therapy yields favorable results in women with early breast cancer into the second decade after treatment.

Using PSA, biopsy Gleason score, clinical stage, and the percentage of positive biopsies to identify optimal candidates for prostate-only radiation therapy.

PURPOSE: An identification of prostate cancer patients most likely to benefit from prostate-only radiation was made based upon the pretreatment prostate-specific antigen (PSA), biopsy Gleason score, clinical stage, percentage of positive biopsies, and the 5-year postoperative PSA outcome. METHODS: Between 1989 and 2000, 2099 patients underwent radical prostatectomy for clinically localized prostate cancer. The primary end points were pathologic evidence of seminal vesicle invasion 2(SVI), extracapsular extension (ECE) with or without positive surgical margins, and the 5-year postoperative PSA outcome. RESULTS: Pretreatment PSA, biopsy Gleason score, and clinical stage were used to assign patients to low-, intermediate-, and high-risk groups. These risk groups were stratified by the percentage of positive biopsies and the primary pathologic and biochemical outcomes examined. The rates of SVI, ECE with positive margin, and no biochemical evidence of disease (bNED) for low-risk patients with < or =50% positive biopsies were 2%, 7%, and 93%, respectively. Patients with >50% positive biopsies had higher rates of SVI and ECE (5% and 11%, respectively) and 52% bNED (p < 0.0001). For intermediate-risk patients with < or =17% positive biopsies, the rates of SVI, ECE with positive margin, and bNED were 3%, 9%, and 90%, respectively. As the percentage of positive biopsies increased above 17% in intermediate-risk patients, there was a statistically significant increase in SVI and ECE and a significant decrease in bNED. CONCLUSIONS: Low-risk patients with < or =50% positive biopsies and intermediate-risk patients with < or =17% positive biopsies had a very low risk of SVI and ECE with positive surgical margins. Given that the presence of SVI and ECE with positive surgical margins was uncommon (<10%) with a > or =90% PSA failure-free survival after radical prostatectomy, these patients may be optimal candidates for radiation therapy directed at the prostate only (prostate gland + 1.5-cm margin).

Quantifying the impact of seminal vesicle invasion identified using endorectal magnetic resonance imaging on PSA outcome after radiation therapy for patients with clinically localized prostate cancer.

PURPOSE: This study examined the impact that seminal vesicle invasion (SVI), observed on endorectal magnetic resonance imaging (erMRI), had on prostate-specific antigen (PSA) outcome after external beam radiation therapy (EBRT) for patients with clinically localized prostate cancer. METHODS AND MATERIALS: The study cohort was comprised of 250 patients who received 3D conformal radiation therapy without hormones for clinically localized prostate cancer between 1992 and 2001. The primary end point was PSA failure, defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Cox regression multivariable analysis was used to determine the ability of the pretreatment risk group and erMRI SVI to predict for time to PSA failure after EBRT. RESULTS: Both risk group (p(Cox) = 0.001) and erMRI SVI (p(Cox) = 0.003) were independent and significant predictors of time to PSA failure. For patients beyond low risk, 4-year estimates of PSA failure-free survival for erMRI SVI-negative vs. erMRI SVI-positive patients were 68% vs. 33% (p(log-rank) = 0.0014), respectively. CONCLUSION: Patients with clinically localized disease and PSA >10 or biopsy Gleason score >or=7 or clinical T category T2b or T2c who also have erMRI evidence of SVI have PSA outcomes similar to patients with locally advanced prostate cancer after EBRT monotherapy. Consideration should be given to combining EBRT with hormonal therapy in these patients.

The impact of pathology review on treatment recommendations for patients with adenocarcinoma of the prostate.

This study was designed to estimate the frequency with which changes in Gleason score because of a genitourinary pathologist's review changed prostate cancer treatment recommendations. The study cohort consisted of 602 patients who presented to a genitourinary oncologist for a second opinion after being diagnosed with prostate cancer based on a needle biopsy at a nonacademic institution from 1989 through 2001. Each of the prostate biopsy specimens was sent for review by a genitourinary pathologist. Applying the rule that low-risk patients would receive monotherapy, and intermediate or high-risk patients would receive combined modality therapy, the frequency with which treatment recommendations were changed by pathology review was calculated. Pathology review by a genitourinary pathologist changed the Gleason score by at least 1 point in 44% of cases. Upgrades were more common than downgrades and accounted for 81% [95% confidence interval: 76-86%] of the changes. Patients' risk category was increased in 10.8% of cases and was decreased in 3.4%. Risk category was changed from low risk to intermediate or high risk in 8.2%, but was changed from intermediate or high risk to low risk in only 0.9%. Genitourinary pathology review would have changed management in approximately 10% of men, mainly in the direction of combined therapy over monotherapy.

Impact on rectal dose from the use of a prostate immobilization and rectal localization device for patients receiving dose escalated 3D conformal radiation therapy.

PURPOSE: When >25% of the rectum is irradiated to > or = 70 Gy, the risk of developing Grade 2 or higher rectal complications is significantly increased. This study evaluates the impact on dose to the rectum from the use of an intrarectal (IR) balloon device, previously shown to immobilize the prostate gland and localize the rectum, in patients receiving dose escalated 3-dimentional (3D) conformal radiation therapy. MATERIALS AND METHODS: From July 2001 through February 2003, 28 consecutive patients with prostate cancer underwent computerized tomography-based simulation with and without the IR balloon in place. Treatment planning was performed for three clinical paradigms in which the IR balloon was not used at all (0 Gy), used during the cone-down for 15 treatments (28.35 Gy), or used for the entire course of 40 treatments (75.6 Gy). The three plans were compared for differences in the percent of rectum receiving >70 Gy. RESULTS: Dose volume histogram (DVH) analysis revealed that the median(range) of percent rectal volume exceeding 70 Gy was 25% (12.7-41.5%), 7.5% (0.9-19.5%), and 3.6% (0-8.7%) for patients in whom the IR balloon was used for 0, 15, and 40 treatments, respectively. The percent of rectum exceeding 70 Gy was significantly different for all treatment plan comparisons (P < 0.0001). CONCLUSIONS: Grade 2 or higher rectal toxicity may be minimized during dose escalated 3D conformal radiation therapy through the use of an IR balloon during the 3-week cone down portion of an 8-week treatment course.

Downstaging of Breast Carcinomas in Older Women Associated with Mammographic Screening.

The efficacy of mammographic screening for older women has not been well studied. The present study was designed to evaluate for downstaging of breast carcinomas associated with mammographic screening in older women. The study population consisted of 130 women age >/=65 years with newly diagnosed breast carcinoma in 1993-1994 and was obtained from women enrolled in a large health maintenance organization. Mammographic screening, if done, was performed by a network of predominantly community-based radiologists. Significant downstaging was found for the breast cancers detected in women who had undergone mammographic screening compared to the breast cancers detected in women who had not undergone mammographic screening. The American Joint Committee on Cancer (AJCC) clinical stage was stage 0 and stage I in 7% (8/107) and 73% (78/107), respectively, of the breast cancers detected in women who had undergone mammographic screening compared to 0% (0/23) and 22% (5/23), respectively, of the breast cancers detected in women who had not undergone mammographic screening (p < 0.0001). Clinical Tis and T1 tumors were found in 7% (8/107) and 74% (79/107), respectively, of the breast cancers detected in women who had undergone mammographic screening compared to 0% (0/23) and 22% (5/23), respectively, of the breast cancers detected in women who had not undergone mammographic screening (p < 0.0001). Of the 102 AJCC clinical stage I-II breast cancers with known pathologic axillary lymph node staging, lymph node stage was N0 for 76% (66/87) of the women who had undergone mammographic screening compared to 53% (8/15) of the women who had not undergone mammographic screening (p = 0.019). The results of downstaging reported in this study are important because earlier staged lesions are associated with an improved prognosis and an increased potential for breast-conservation treatment. These findings have shown that mammographic screening is effective in downstaging breast carcinomas found in older women.

Radical prostatectomy for high-grade prostate cancer.

OBJECTIVES: Patients with high-grade clinically localized disease often have disease beyond the prostate and, if so, are unlikely to benefit from radical prostatectomy in the long-term. The objective of this study was to assess whether use of other known prognostic factors could be helpful in defining which men with Gleason 8 to 10 prostate cancer are most likely to benefit from surgical management. METHODS: A retrospective analysis was performed on men with biopsy Gleason 8 to 10 prostate cancer who underwent radical prostatectomy at two major university centers. No patients received hormonal therapy as part of initial treatment or adjuvant radiation therapy. Surgery was performed using a retropubic approach, and lymph node dissection was performed in all patients. Risk groups were defined based on prostate-specific antigen (PSA) value and percent positive biopsy cores (%PBC). A Cox proportional hazards analysis was performed to assess for differences in pretreatment prognostic factors. Kaplan-Meier curves were generated for each group, and then comparisons between groups were performed using log-rank analysis to assess for differences in 5-year actuarial freedom from biochemical failure. RESULTS: Radical prostatectomy was performed on 196 patients between 1987 and 2002, of whom 168 had sufficient data for analysis. Median follow-up was 18 months (range, 1 to 130 months), with 31 patients at risk for more than 5 years. Patients with a PSA value of less than 10 ng/mL and %PBC of less than 50% had a 5-year actuarial biochemical control rate of 67% versus 23% for all other patients (P = 0.0001). CONCLUSIONS: PSA value and %PBC are useful in selecting patients with high-grade prostate cancer most likely to benefit by radical prostatectomy.

Predictors of short postoperative prostate-specific antigen doubling time for patients diagnosed during PSA era.

OBJECTIVES: To determine the preoperative and postoperative predictors of a short prostate-specific antigen (PSA) doubling time (PSADT) after radical prostatectomy for patients diagnosed during the PSA era. METHODS: Between 1989 and 2003, 1785 men underwent radical prostatectomy for 2002 American Joint Committee on Cancer (AJCC) Stage T1c or T2 prostate cancer. Of these men, 205 had documented PSA failure. The PSADT was calculated by assuming first-order kinetics and using a minimum of two detectable postoperative PSA measurements after a previous undetectable level. Multivariable logistic regression analyses were performed to determine the significant preoperative and postoperative predictors of a PSADT of less than 6 months. RESULTS: Patients with a greater biopsy Gleason score (P = 0.006), greater preoperative risk group (P = 0.002), greater prostatectomy Gleason score (P = 0.0006), greater 2002 AJCC pathologic stage (P = 0.01), or shorter time to postoperative PSA failure (P = 0.04) were more likely to have a shorter PSADT. Using multivariable analysis, high-risk disease (P = 0.0001) was the only preoperative factor that remained an independent significant predictor of a PSADT of less than 6 months. Of the postoperative factors, a prostatectomy Gleason score of 8 to 10 (P = 0.002), 2002 AJCC pathologic Stage T3b (P = 0.03), and time to PSA failure of less than 2 years (P = 0.05) remained significant independent predictors of a PSADT of less than 6 months. CONCLUSIONS: High-risk disease preoperatively and a prostatectomy Gleason score of 8 to 10, seminal vesicle invasion, or a time to PSA failure of less than 2 years postoperatively were significant independent indicators of developing a postoperative PSADT of less than 6 months. For these men, trials studying systemic therapy in addition to radical prostatectomy are needed.

Acute urinary retention after magnetic resonance image-guided prostate brachytherapy with and without neoadjuvant external beam radiotherapy.

OBJECTIVES: To evaluate the risk of acute urinary retention (AUR) and sequelae after urethra-sparing magnetic resonance imaging (MRI)-guided prostate brachytherapy. METHODS: Between 1997 and 2003, MRI-guided prostate brachytherapy was performed after external beam radiotherapy (n = 60) or as monotherapy (n = 188) following a diagnosis of low-risk prostate adenocarcinoma. The median prostate gland volume was 40 cm3 (range 16 to 184). Of the 248 patients, 88 (35%) had prostate gland volumes greater than 45 cm3. The median follow-up was 40 months. RESULTS: Of the 248 patients, 18 (7%) developed AUR. Of the 248 patients, 2% (3 of 160), 6% (3 of 49), 28% (8 of 29), and 40% (4 of 10) of patients experienced AUR if the prostate gland volume was less than 45, 45 to 60, 60 to 90, or greater than 90 cm(3), respectively (P <0.0001). Retention requiring intermittent self-catheterization resolved in one half of the patients by 2 weeks and had resolved in all patients by 6 weeks. At 1, 3, and 6 months after implantation, 100%, 57%, and 29% of patients who experienced AUR, respectively, used Flomax (P <0.0001). The mean Flomax dose used decreased from 0.9 mg at 1 month to 0.53 mg at 1 year. CONCLUSIONS: AUR after urethral-sparing MRI-guided prostate brachytherapy is volume dependent and is self-limited despite very large prostate gland volumes.

The impact of a delay in initiating radiation therapy on prostate-specific antigen outcome for patients with clinically localized prostate carcinoma.

BACKGROUND: To determine whether a delay in initiating external beam radiation therapy (RT) following diagnosis could impact prostate-specific antigen (PSA) outcome for patients with localized prostate cancer, 460 patients, who received 3D conformal RT to a median dose of 70.4 Gy for clinically localized prostate cancer between 1992 and 2001, were studied. METHODS: The primary endpoint was PSA failure (American Society for Therapeutic Radiology and Oncology definition). Estimates of PSA control were made using the Kaplan-Meier method. Delay was defined as the time between diagnosis and the start of RT. Risk groups were defined based on known predictors of PSA outcome, namely, baseline PSA level, clinical T-category, Gleason score, and percentage of biopsy cores positive for tumor. Cox multivariate regression analysis was used to determine the ability of treatment delay to predict time to PSA failure after adjusting for the other known predictors. RESULTS: Treatment delay independently predicted time to PSA failure following diagnosis for high-risk (Adjusted Hazard Ratio = 1.08 per month; P = 0.029) but not low-risk patients (P = 0.31). Patients with high-risk disease (n = 240) had 5-year estimates of PSA failure-free survival of 55% versus 39% (Plog-rank = 0.014) for those with delay < 2.5 months versus > or = 2.5 months respectively. The median delay was 2.5 months. CONCLUSIONS: Treatment delay adversely affected PSA outcome for high-risk patients but not for low-risk patients following RT.

Factors associated with residual disease on re-excision in patients with ductal carcinoma in situ of the breast.

PURPOSE: This study examines the factors associated with the presence of residual disease at re-excision in patients with ductal carcinoma in situ of the breast. METHODS: Of 143 consecutive patients undergoing breast conservation treatment from 1990 to 1999, 90 patients (63%) underwent re-excision of the tumor bed. Grade was recorded in 70% (N = 63), size in 78% (N = 70), margin status in 96% (N = 86), volume of excision in 90% (N = 81), and extent of residual disease in 99% (N = 89). RESULTS: There was no significant correlation between extent of residual disease on re-excision and method of detection, tumor size, histology, grade, or first margin status. Of patients undergoing re-excision, 56% (N = 50) had no residual disease, 38% (N = 34) had minimal microscopic residual disease, and only 6% (N = 5) had either extensive microscopic or gross residual disease. For these five patients, the median volume of first excision was similar to that of the other patients (26 vs 36 cc), but the median volume of second excision was smaller (33 vs 63 cc). The median age for these five patients was 41 years, compared with 55 years for the remaining patients. All five patients had comedo (N = 4) or solid tumor (N = 1) histology, with grade 3 (N = 3) or unknown grade (N = 2). DISCUSSION: Patients with extensive microscopic disease or gross residual at the time of re-excision would be at increased risk for local recurrence after conventional radiation treatment if re-excision had not been performed. Only 6% of patients in this study had such pathology findings. No factor predicted for these adverse pathology findings, although these patients tended to be younger, with high-grade or comedo histology.

Determinants of prostate cancer specific survival following radiation therapy during the prostate specific antigen era.

PURPOSE: Identifying pretreatment and posttreatment predictors of time to prostate cancer specific death (PCSD) following external beam radiation therapy (RT) is the subject of this study. MATERIALS AND METHODS: A Cox regression analysis was used to evaluate the ability of the pretreatment risk group to predict time to PCSD for 381 patients who underwent RT for clinically localized prostate cancer. Posttreatment factors analyzed for the 94 patients who experienced prostate specific antigen (PSA) failure included the time to failure, posttreatment PSA doubling time (DT) and timing of salvage hormonal therapy. RESULTS: Despite a median age of 73 at diagnosis, 45% of patients with high risk disease were estimated to die of prostate cancer within 10 years following RT compared to 0% (p = 0.004) and 6% (p = 0.05) of those with low or intermediate risk disease, respectively. Predictors of time to PCSD following PSA failure included PSA DT (p = 0.01) and delayed use of hormonal therapy (p