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Background: Men with high-risk prostate cancer are often thought to have very poor outcomes in terms of disease control and survival even after definitive treatment. However, results after external beam radiotherapy have improved significantly through dose escalation and the use of androgen deprivation therapy (ADT). This report describes long-term findings after low-dose (< 75.6 Gy) or high-dose (≥ 75.6 Gy) external beam radiation, with or without ADT., Methods: This analysis included 741 men with high-risk prostate cancer (clinical classification ≥ T3, Gleason score ≥ 8, or prostate-specific antigen level ≥ 20 ng/mL) treated with external beam radiotherapy at a single tertiary institution from 1987 through 2004. The radiation dose ranged from 60 to 79.3 Gy (median, 70 Gy); 295 men had received ADT for ≥ 2 years, and the median follow-up time was 8.3 years., Results: The 5- and 10-year actuarial overall survival rates were significantly better for men treated with the higher radiation dose (no ADT plus ≥ 75.6 Gy, 87.3% and 72.0%, respectively; and ADT plus ≥ 75.6 Gy, 92.3% and 72%, respectively) (P = .0035). The corresponding 5- and 10-year biochemical failure-free survival rates were significantly better for patients treated with both ADT and higher radiation dose (82% and 77%, P < .0001). At 5 years, men who had not received ADT and had received radiation dose < 75.6 Gy had higher clinical local failure rates than those given ADT and radiation dose ≥ 75.6 Gy (24.2% versus 0%, P < .0001). The 10-year symptomatic local failure rate was only 2% for all patients., Conclusions: Contrary to lingering historical perceptions, treatment of high-risk prostate cancer with modern, high-dose, external beam radiotherapy and ADT can produce better biochemical, clinical, and survival outcomes over those from previous eras. Specifically, symptomatic local failure is uncommon, and few men die of prostate cancer even 10 or more years after treatment., (© 2013 American Cancer Society.)

Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA < 10 ng/mL, Gleason score < or =6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores > or =7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy.

Background: Several reports have shown that obesity is associated with increased risk of biochemical failure after radical prostatectomy. However, limited information is available regarding the impact of obesity on prostate cancer progression after radiotherapy. The current study sought to determine whether obesity was an independent predictor of biochemical failure (BF) and clinical recurrence (CF) among patients treated with external-beam radiotherapy (EBRT)., Methods: A retrospective analysis was performed on 873 patients receiving EBRT as the sole treatment for localized prostate cancer between 1988 and 2001. The Kaplan-Meier method, log-rank test, and Cox proportional hazards analyses were performed., Results: Of the 873 patients, 18% were mildly obese and 5% were moderately to severely obese. Obesity was related to younger age at diagnosis (P < .001), more recent year of diagnosis (P = .03), and race (P = .03), with African-American men having the highest obesity rates. During a mean follow-up of 96 months, 295 patients experienced BF and 127 had CF. On multivariate analysis, controlling for clinical and treatment characteristics, increased body mass index (BMI) significantly predicted BF (hazards ratio [HR] = 1.04; 95% confidence interval [95% CI], 1.02-1.07) with a positive trend by BMI category (P = .001). Similar results were found when the outcome was CF; BMI remained an independent predictor of progression (HR = 1.05; 95% CI, 1.01-1.09), with a statistically significant trend by increased BMI category (P = .03)., Conclusions: The current findings validate the important role of obesity, not only on BF but also on CF, and suggest a link to the biologic basis of tumor progression that can be therapeutically exploited., (Copyright 2006 American Cancer Society.)

Background: The value of presalvage cryotherapy serum PSA level in predicting biochemical failure in patients with local recurrence of prostate cancer (PCa) after radiotherapy was documented; however, little is known about the predictive value of prostate-specific antigen (PSA) doubling time (DT) in this patient group. The purpose of the current study was to evaluate serum PSA level and PSA DT as predictors of salvage cryotherapy outcomes in patients being treated for postradiotherapy locally recurrent PCa., Methods: The charts of patients treated with salvage cryotherapy were retrospectively reviewed for locally recurrent PCa at the M. D. Anderson Cancer Center from January 1980 to July 2004. Patients who received neoadjuvant or adjuvant hormone therapy were excluded. We assessed pre- and postradiotherapy clinical data, pre- and postsalvage cryotherapy clinical data, and other variables. Kaplan-Meier and log rank tests were performed to assess unadjusted survival probabilities and 2-group survival comparisons, respectively. Cox proportional hazards regression models were used to assess the effect of patient characteristics in predicting overall, disease-specific, and biochemical failure-free survival., Results: Forty-nine patients met the eligibility criteria. The median age of patients at diagnosis was 66 years (58-81 years) with the initial clinical stage before radiotherapy most commonly T2 (n = 25) or T3 (n = 21). The median presalvage cryotherapy serum PSA level was 5.9 ng/mL (0.4-23.1 ng/mL) and the presalvage prostatic biopsies were frequently high grade (Gleason grade > or =8 in 51% of patients). The median postsalvage cryotherapy serum PSA level was 0.1 ng/mL (0.1-9.5 ng/mL), and biochemical failure (defined as a serum PSA level > or =2 ng/mL above the postsalvage cryotherapy PSA nadir) occurred in 26 patients. In these 26 patients, there was a statistically significant difference between pre- and postsalvage cryotherapy PSA DTs (12.3 months to 5.6 months, respectively; P = .02). A presalvage cryotherapy serum PSA level >10 ng/mL (P = .002) and PSA DT < or =16 months (P = .06) were found to predict the subsequent risk of biochemical failure., Conclusions: Presalvage PSA and PSA DT can predict biochemical failure of salvage cryotherapy, although the predictive value of PSA DT only trended toward significance. The statistically significant difference in pre- and postsalvage cryotherapy PSA DTs was reflective of aggressive tumor biology.

Background: Symptomatic local recurrence of prostate carcinoma (SLRPC) after radiation therapy (RT) is associated with morbidity and debilitating symptoms that have a substantial impact on the patient's quality of life. Most reports on the results of RT for localized prostate carcinoma (PC) do not address this endpoint. The objective of this study was to determine the incidence of SLRPC and to identify the risk factors for this endpoint., Methods: The medical charts of 1006 patients who received RT for localized PC at the University of Texas M. D. Anderson Cancer Center between 1987 and 1997 were reviewed. Local symptoms were defined as hematuria, voiding symptoms, urinary obstruction, and pelvic pain. Progressive symptoms accompanied by either confirmatory histology or cystoscopic findings were attributed to PC. Univariate and multivariate analyses using Cox proportional hazards models were applied to identify risk predictors., Results: Among 964 patients for whom follow-up data were available, 277 patients had prostate-specific antigen (PSA) progression, and 45 patients died of PC during a median follow-up of 9.4 years. In total, 33 patients (3.4%) developed SLRPC. In patients who experienced biochemical progression, the actuarial 5-year incidence of SLRPC was 8.3%. Among the patients who had developed SLRPC, 23 patients (69.7%) died of PC at a median of 25.3 months from the onset of local symptoms. Adverse histologic tumor subtypes (ductal, small cell, and sarcomatoid) were associated significantly with SLRPC (hazard ratio, 8.4; 95% confidence interval, 2.99-23.63). Clinical T classification at diagnosis, Gleason score, and initial PSA level showed a trend toward an increased hazard ratio., Conclusions: SLRPC after radiotherapy therapy was an uncommon but clinically significant event. Aggressive histologic subtypes were predictive of this endpoint. Clinical T classification, Gleason score, and initial prostate-specific antigen levels also may have predictive value.

Background: Patients with lymph node negative invasive breast carcinomas < or = 1 cm in size have a low recurrence rate and may be spared adjuvant therapy. Reliable prognostic features will help physicians design appropriate treatment for these patients., Methods: The clinicopathologic features, prognostic marker profiles, and clinical outcomes of 88 T1a,bN0M0 carcinomas in 87 patients who presented between 1975 and 1990 were studied. The size of each tumor was determined by direct measurement of histologic sections. The median follow-up was 7.8 years (range, 4-15 years). The characteristics of tumors diagnosed between 1975 and 1983 and between 1984 and 1990 were also compared., Results: Before 1984, the majority of patients presented with palpable mass lesions, whereas from 1984 on, more patients presented with mammographic abnormalities. However, no significant differences in the pathologic features of tumors were observed between the two periods. There were only 3 locoregional recurrences (3%) and 4 distant recurrences (5%). Palpable tumors had worse prognoses than mammographically detected lesions (P = 0.02). Histologic grade, lymphatic invasion, hormone receptors, Ki-67 antigen, and bcl-2 expression were significant univariate prognostic indicators. The small number of patients in the series precluded multivariate analysis. None of the 43 patients (49%) with tumors < or = 0.5 cm, or of histologic and nuclear Grade 1, or of favorable histologic types developed recurrences; and their outcomes were significantly better than those of other patients (P = 0.013). Tumors originally classified as T1b, but which exceeded 1 cm on review and were excluded from the study, had a significantly higher distant recurrence rate (23%) than bona fide T1a,b carcinomas (P = 0.03)., Conclusions: T1a,bN0M0 carcinomas have a low recurrence rate, especially those tumors < or = 0.5 cm, or of low histologic or nuclear grade, or of favorable histologic type. The high recurrence among patients with tumors initially understaged as T1a,b carcinoma underscores the importance of accurately determining tumor size.

Background: Although breast cancer in men is far less common than breast cancer in women, it is associated with a less favorable prognosis. Conventional histopathologic features and new prognostic markers were evaluated to explain the less favorable survival outcome., Methods: Forty-six consecutive male breast carcinomas were studied for size, histologic and nuclear grade, histologic subtype, presence of carcinoma in situ, nipple involvement, lymphovascular invasion, hormone receptor status, c-erbB-2 protein overexpression, and p53 protein accumulation. These findings were correlated with survival., Results: Of the 46 carcinomas, 4 were noninvasive and 42 were invasive. In the invasive carcinomas, the median patient age was 64 years, and the median tumor size was 2 cm. The predominant histologic patterns were invasive ductal (45%) and mixed invasive ductal and cribriform (28%). Most tumors were of low histologic and nuclear grades (histologic grades: I, 17%; II, 50%; III, 33%; nuclear grade: I, 12%; II, 44%; III, 44%). Of those surgically staged, 22 patients (60%) were lymph node positive and 15 patients (40%) were node negative. Stage at presentation was higher than in women (0, 10%; 1, 17%; 2, 50%; 3, 13%; 4, 10%). The estrogen and progesterone receptor status was positive in 76% and 83% of tumors, respectively. Lymphatic vessel invasion (63%) and nipple involvement (48%) were also more common than in women. True Paget's disease of the nipple was not seen; all cases with nipple ulceration were the result of direct tumor extension to the epidermis. Of the 17 tumors tested, 41% were c-erbB-2 positive and 29% were p53 positive. Survival analysis was limited by the relatively small cohort size. Five- and 10-year adjusted overall survival rates for invasive tumors were 76 +/- 7% and 42 +/- 9%, respectively. Skin and nipple involvement (P = 0.03) and c-erbB-2-positivity (P = 0.03) were significant predictors of adverse survival., Conclusions: Male breast carcinoma presents in an advanced stage with less favorable survival, despite low histologic grade, high estrogen receptor content, and small size. Anatomic factors may have been responsible for the poor survival outcome (i.e., paucity of breast tissue and close tumor proximity to skin and nipple, facilitating dermal lymphatic spread and early regional and distant metastasis).

Background: Ductal carcinoma in situ (DCIS) of the male breast is an uncommon disease, accounting for approximately 7% of all male breast carcinomas. Compared with invasive carcinomas of the breast, the prognosis associated with DCIS in men is excellent; however, clinical features, pathology, and treatment of this disease are not well defined in the literature., Methods: Records of 23 men with carcinoma of the breast treated at the Lahey Clinic from 1968 to 1991 were reviewed, revealing 4 patients with pure DCIS (17%). The reported management of DCIS in women is discussed in comparison with that of DCIS in men., Results: Of the four patients with DCIS, the presenting complaint was a retroareolar mass in three patients and a bloody nipple discharge in one patient. The pathologic subtype was papillary in one patient and intracystic papillary in three patients. Two patients were treated with partial mastectomy alone. Disease recurred locally as DCIS in both patients, requiring mastectomy at 30 and 108 months. No lymph node metastases were found in the three patients who underwent axillary dissection. All four patients were alive without disease at 133, 120, 36, and 32 months of follow-up, respectively., Conclusions: Although the sample size was small, our patients and a review of the literature suggest that most DCIS in men is of the papillary type and that mastectomy without axillary dissection is the preferred treatment.

Methods: The prognostic significance of flow cytometric analysis in patients with node-negative invasive breast carcinoma was evaluated in a retrospective series of 158 patients with a minimum follow-up study of 9 years., Results: The ploidy status could be assessed in 147 specimens (93%), and the proliferative phase or S-phase fraction (SPF) could be assessed in 136 tumors (86%); 70 tumors (48%) were diploid, 49 tumors (33%) were aneuploid, and 28 tumors (19%) were tetraploid. Ploidy status and SPF were correlated significantly with tumor size, histologic grade, nuclear grade, and mitotic rate. By itself, ploidy was not a statistically significant prognostic factor, although all of the patients with multiploid and hypertetraploid tumors had recurrence of disease. The SPF was related significantly to recurrence of disease (P = 0.04). However, when multivariate analysis of various histopathologic variables was performed, SPF ceased to be a significant prognostic determinant, whereas peritumoral lymphovascular invasion was the most important variable. The combination of tumor size and flow cytometric parameters permitted stratification into three groups with different prognoses at the 9-year follow-up review (P less than 0.001). In the low-risk group (diploid tumors less than or equal to 2 cm in diameter with a low SPF or small tetraploid tumors), the recurrence rate was 12%. In the intermediate-risk group (diploid tumors greater than 2 cm in diameter with a low SPF or aneuploid tumors with a low SPF), the recurrence rate was 21%. In the high-risk group (diploid or aneuploid tumors with a high SPF or large tetraploid tumors), the recurrence rate was 49%. The high-risk group status remained a significant variable in the Cox proportional hazards multivariate analysis model., Conclusions: These results indicate that flow cytometry in breast carcinoma contributes useful but limited prognostic information and stress the importance of using multiple prognostic factors to improve prognostication and optimize patient management.