Biochemical recurrence rates are similar for pT2-positive surgical margins and pT3a.

OBJECTIVE: Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy. MATERIALS AND METHODS: Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence. RESULTS: 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7. CONCLUSION: Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.

Association between integrin expression and prognosis in localized prostate cancer.

BACKGROUND: Integrins and other adhesion molecules are essential for maintaining the epithelial phenotype. Some studies have reported correlations between abnormalities in their expression and carcinogenesis, but their role in prostate cancer is unclear. Our aim was to study the expression profile of integrins in surgical specimens of prostate cancer and associate their expression patterns with patient outcomes. METHODS: We selected 111 patients with localized prostate cancer who had undergone radical prostatectomy. Of these patients, 60 had no tumor recurrence after a median follow-up of 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two tumor samples per patient. A semiquantitative analysis was employed. We measured the association between the expression of eight integrins and tumor recurrence. RESULTS: Multivariate analysis showed that expression of alpha3 and alpha3beta1 was related to worse outcome. When alpha3 expression was strong and alpha3beta1 expression was positive, the odds of recurrence were 3.0- and 2.5-fold higher, respectively. Only 19% and 28% of patients were recurrence-free in a mean period of 123 months of follow up when their tumors showed strong alpha3 or positive alpha3beta1 immuno-expression, respectively. CONCLUSIONS: We have shown that the expression of integrin alpha3beta1 was independently associated with tumor recurrence after radical prostatectomy, suggesting that this integrin is a potential prognostic marker.

Perineural invasion detection in prostate biopsy is related to recurrence-free survival in patients submitted to radical prostatectomy.

OBJECTIVE: Perineural invasion (PNI) is detected in almost 20% of prostate biopsies and has been related to worse prognostic factors in radical prostatectomy (RP) specimens and lower disease-free survival rates. The aim of this study was to evaluate the importance of PNI during periods of extended prostate biopsies and to determine the value of this preoperative parameter as a predictor of pathologic findings in surgical specimens and in biochemical recurrence. MATERIALS AND METHODS: Between 2001 and 2009, 599 prostate biopsies and their respective RP specimens were examined in our laboratory. The RP specimens were always examined completely. The mean age of the patients was 61 years, and the mean PSA was 6.4 ng/mL. The mean and median number of biopsy cores obtained was 14.4 and 14, respectively. PNI was identified in 105 biopsies (17.5%). We studied the ability of PNI in prostate biopsies to determine the tumor stage in surgical specimens and the relationship of PNI with biochemical recurrence during a mean follow-up time of 51.4 months. RESULTS: The presence of PNI in prostate biopsies was observed in older patients (63 vs. 61 years old, P = 0.008). All of the prognostic factors determined for the RP specimens were significantly worse in patients with PNI compared with those without PNI. PNI was strongly associated with a higher pathologic stage (87% specificity, 40% sensitivity, odds ratio 4.8). Stage pT3 prostatic cancer was determined in 46 (43.8%) of 105 patients with PNI on biopsy compared to 69 (14%) of 494 patients without PNI (P = 0.01). Fifty-six (19.6%) patients had a biochemical recurrence, and PNI correlated significantly with PSA recurrence. A Kaplan-Meier analysis revealed a significant difference in recurrence-free survival between patients with and without PNI (45% vs. 53%, respectively, P = 0.021, log-rank test = 0.19). CONCLUSION: PNI is an important morphologic preoperative predictor of the pathologic stage as well as biochemical recurrence and must always be mentioned when adenocarcinoma is diagnosed on prostate biopsies.

Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy?

INTRODUCTION AND OBJECTIVE: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. MATERIAL AND METHODS: A total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a-b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. RESULTS: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a-b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ≥ 7, and 25% were staged pT3. CONCLUSION: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated.

Biochemical recurrence rates are similar for pT2-positive surgical margins and pT3a

Objective Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy.Materials and Methods Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence.Results 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7.Conclusion Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.

Sarcomatoid differentiation in renal cell carcinoma: prognostic implications.

INTRODUCTION: Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS: We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumor's pathological features, use of adjuvant immunotherapy and survival. The study's primary end-point was to assess survival of these individuals. RESULTS: The sample included 8 women and 7 men with mean age of 63 years (44-80); follow-up ranged from 1 to 100 months (mean 34). Upon presentation, 87% were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4-24) with the following pathological stages: 7% pT1, 7% pT2, 33% pT3, and 53% pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87% of the lesions and 80% of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46% respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS: Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

Prognostic value of the percentage of positive fragments in biopsies from patients with localized prostate cancer.

OBJECTIVE: To assess the prognostic value of the percentage of positive fragments (PPF) in biopsies from patients with localized prostate cancer (PCa) undergoing radical prostatectomy. MATERIALS AND METHODS: During the period from March 1991 to November 2000, 440 patients were selected. Cases receiving neoadjuvant or adjuvant hormone therapy, or adjuvant radiotherapy, were excluded, as were cases presenting Gleason scores higher than 6 at biopsy. PPF was defined as the total number of fragments divided by the total number of biopsy fragments times 100. This variable was initially divided into categories from 0 to 25%, 25.1% to 50%, 50.1 to 75% and 75% to 100%. During the postoperative period, patients were assessed every 2 months for 1 year, then every 6 months for 5 years, and then yearly. Biochemical recurrence was defined as serum PSA higher than or equal to 0.4 ng/mL. Median follow-up was 60 months. RESULTS: One hundred and nine (24.8%) of the 440 patients under study had biochemical recurrence. In the univariate analysis, PPF significantly influenced disease-free survival (log-rank, p < 0.001), and patients with PPF between 75 and 100% presented a risk of a biochemical recurrence of the disease 3 times higher than patients with PPF between 0 and 25% (p < 0.001). After the Cox regression analysis, both serum PSA (p = 0.001) and PPF (p < 0.001) showed to be independent predictive factors for disease-free survival following surgery. CONCLUSION: PPF measurement in biopsy is a simple and practical method, which should be routinely used as a predictive factor for biochemical recurrence in patients with PCa presenting Gleason scores between 2 and 6.

Analysis of risk factors of involvement of seminal vesicles in patients with prostate cancer undergoing radical prostatectomy.

OBJECTIVE: To determine through preoperative serum PSA level, Gleason score on biopsy and percentage of fragments affected by tumor on biopsy, the probability of involvement of the seminal vesicles. MATERIALS AND METHODS: During the period between March 1991 to December 2002, we selected 899 patients undergoing radical prostatectomy for treatment of localized prostate adenocarcinoma. The analyzed preoperative variables were PSA, percentage of positive fragments and Gleason score on the biopsy. Pre-operative PSA was divided in scales from 0 to 4.0 ng/mL, 4.1 to 10 ng/mL, 10.1 to 20 ng/mL and > 20 ng/mL, Gleason score was categorized in scales from 2 to 6. 7 and 8 to 10, and the percentage of affected fragments was divided in 0 to 25%, 25.1% to 50%, 50.1% to 75%, and 75.1% to 100%. All these variables were correlated with the involvement of seminal vesicles in the surgical specimen. RESULTS: Of the 899 patients under study, approximately 11% (95% CI, [9% - 13%]) had involvement of seminal vesicles. On the multivariate analysis, when PSA was < or = 4, the Gleason score was 2 to 6, and less than 25% of fragments were involved on the biopsy, only 3.6%, 7.6% and 6.2% of patients respectively, had involvement of seminal vesicles. On the multivariate analysis, we observed that PSA, Gleason score and the percentage of involved fragments were independent prognostic factors for invasion of seminal vesicles. CONCLUSION: The preoperative variables used in the present study allow the identification of men with minimal risk (lower than 5%) if involvement of seminal vesicles.

Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

INTRODUCTION: Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS: We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumor's pathological features, use of adjuvant immunotherapy and survival. The study's primary end-point was to assess survival of these individuals. RESULTS: The sample included 8 women and 7 men with mean age of 63 years (44 - 80); follow-up ranged from 1 to 100 months (mean 34). Upon presentation, 87 percent were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4 - 24) with the following pathological stages: 7 percent pT1, 7 percent pT2, 33 percent pT3, and 53 percent pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87 percent of the lesions and 80 percent of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46 percent respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS: Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

Prognostic value of the percentage of positive fragments in biopsies from patients with localized prostate cancer

OBJECTIVE: To assess the prognostic value of the percentage of positive fragments (PPF) in biopsies from patients with localized prostate cancer (PCa) undergoing radical prostatectomy. MATERIALS AND METHODS: During the period from March 1991 to November 2000, 440 patients were selected. Cases receiving neoadjuvant or adjuvant hormone therapy, or adjuvant radiotherapy, were excluded, as were cases presenting Gleason scores higher than 6 at biopsy. PPF was defined as the total number of fragments divided by the total number of biopsy fragments times 100. This variable was initially divided into categories from 0 to 25 percent, 25.1 percent to 50 percent, 50.1 to 75 percent and 75 percent to 100 percent. During the postoperative period, patients were assessed every 2 months for 1 year, then every 6 months for 5 years, and then yearly. Biochemical recurrence was defined as serum PSA higher than or equal to 0.4 ng/mL. Median follow-up was 60 months. RESULTS: One hundred and nine (24.8 percent) of the 440 patients under study had biochemical recurrence. In the univariate analysis, PPF significantly influenced disease-free survival (log-rank, p < 0.001), and patients with PPF between 75 and 100 percent presented a risk of a biochemical recurrence of the disease 3 times higher than patients with PPF between 0 and 25 percent (p < 0.001). After the Cox regression analysis, both serum PSA (p = 0.001) and PPF (p < 0.001) showed to be independent predictive factors for disease-free survival following surgery. CONCLUSION: PPF measurement in biopsy is a simple and practical method, which should be routinely used as a predictive factor for biochemical recurrence in patients with PCa presenting Gleason scores between 2 and 6.

Analysis of risk factors of involvement of seminal vesicles in patients with prostate cancer undergoing radical prostatectomy

OBJECTIVE: To determine through preoperative serum PSA level, Gleason score on biopsy and percentage of fragments affected by tumor on biopsy, the probability of involvement of the seminal vesicles. MATERIALS AND METHODS: During the period between March 1991 to December 2002, we selected 899 patients undergoing radical prostatectomy for treatment of localized prostate adenocarcinoma. The analyzed preoperative variables were PSA, percentage of positive fragments and Gleason score on the biopsy. Pre-operative PSA was divided in scales from 0 to 4.0 ng/mL, 4.1 to 10 ng/mL, 10.1 to 20 ng/mL and > 20 ng/mL, Gleason score was categorized in scales from 2 to 6. 7 and 8 to 10, and the percentage of affected fragments was divided in 0 to 25 percent, 25.1 percent to 50 percent, 50.1 percent to 75 percent, and 75.1 percent to 100 percent. All these variables were correlated with the involvement of seminal vesicles in the surgical specimen. RESULTS: Of the 899 patients under study, approximately 11 percent (95 percent CI, [9 percent - 13 percent]) had involvement of seminal vesicles. On the multivariate analysis, when PSA was < 4, the Gleason score was 2 to 6, and less than 25 percent of fragments were involved on the biopsy, only 3.6 percent, 7.6 percent and 6.2 percent of patients respectively, had involvement of seminal vesicles. On the multivariate analysis, we observed that PSA, Gleason score and the percentage of involved fragments were independent prognostic factors for invasion of seminal vesicles. CONCLUSION: The preoperative variables used in the present study allow the identification of men with minimal risk (lower than 5 percent) if involvement of seminal vesicles.