Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

PURPOSE: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). METHODS: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. RESULTS: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). CONCLUSIONS: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

Predictive factors of oncologic outcomes in patients who do not achieve undetectable prostate specific antigen after radical prostatectomy.

PURPOSE: We identified factors predicting oncologic outcomes in cases of persistently detectable prostate specific antigen. MATERIALS AND METHODS: We reviewed the charts of patients treated with radical prostatectomy between 1998 and 2011 at a total of 14 centers. Study inclusion criteria were radical prostatectomy for presumed localized prostate cancer, absent positive nodes and detectable prostate specific antigen, defined as prostate specific antigen 0.1 ng/ml or greater 6 weeks postoperatively. Of the 9,735 radical prostatectomy cases reviewed 496 (5.1%) were eligible for analysis. Predictive factors for oncologic outcomes were assessed in time dependent analyses using the Kaplan-Meier method and Cox regression models. RESULTS: At 6 weeks prostate specific antigen was 0.1 to 6.8 ng/ml. Biochemical progression was noted in 74.4% of patients and clinical metastasis was noted in 5%. The 2 most powerful predictors of general salvage treatment (vs radiotherapy) were postoperative prostate specific antigen greater than 1 ng/ml (OR 3.46, p=0.032) and prostate specific antigen velocity greater than 0.2 ng/ml per year (HR 6.01, p=0.001). Positive prostate specific antigen velocity was the single factor that independently correlated with the risk of failed salvage therapy (HR 2.6, p=0.001). The 5-year disease-free survival rate was 81.0% in patients with stable or negative prostate specific antigen velocity compared with 58.4% in those with positive prostate specific antigen velocity (p<0.001). CONCLUSIONS: Patients with detectable prostate specific antigen after radical prostatectomy have a poor biochemical outcome. We identified postoperative prostate specific antigen and prostate specific antigen velocity as independent predictors of progression and failed salvage treatment. In addition to pathological prognostic factors, these factors should be considered early to better stratify patients for adjuvant therapy.

Capsular involvement in patients undergoing partial nephrectomy for localized renal cell carcinoma: an adverse pathological finding?

OBJECTIVE: To evaluate the prognostic impact of capsular involvement (CaI) in patients treated exclusively with partial nephrectomy (PN) for localized renal cell carcinoma (RCC), as in these patients CaI was recently reported as an adverse prognostic factor. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients treated with PN for a sporadic and localized RCC (pT1-pT2N0M0) in our institution between 1985 and 2005. Univariate and multivariate analysis using a Cox proportional-hazards regression analysis were conducted to identify significant predictors of oncological outcome for several clinical and pathological factors, i.e. imperative indication, histological type, Fuhrman grade, tumour size, T stage, CaI, and surgical margins. Disease-free and -specific survival rates of patients with CaI and no evidence of CaI were compared using the log-rank test. RESULTS: In all, 305 patients had a PN for localized RCC, of whom 22 (7.2%) had CaI in the PN specimen. The median (range) follow-up was 6 (1.5-23) years. Multivariate statistical analysis showed that imperative indication for PN and high-grade RCC were independently associated with worse disease-free and -specific survival, whereas CaI had no prognostic value. Disease-free and -specific survival in patients with and without CaI were not significantly different at 5 and 10 years. CONCLUSIONS: In a contemporary series of patients exclusively treated with PN for localized RCC, CaI was not predictive of disease recurrence and disease-specific mortality. These results do not support the use of any change in postoperative management in patients with CaI after PN.

Pathologic findings in radical prostatectomy specimens from patients eligible for active surveillance with highly selective criteria: a multicenter study.

OBJECTIVE: To evaluate the pathologic features of surgical specimens after radical prostatectomy in patients with low-risk prostate cancer fulfilling the strictest pathologic selection criteria for active surveillance. METHODS: Retrospective analysis of 10 785 consecutive radical prostatectomy performed in 10 university hospitals (January 2003 through December 2008). A total of 919 patients fulfilled the following unique and very stringent criteria: T1c, prostate-specific antigen (PSA) <10 ng/mL, a single positive biopsy, tumor length <3 mm, and Gleason score <7. Clinico-biologic and pathologic data at diagnosis and after radical prostatectomy, prostatic and tumor volume, pathologic Gleason score and stage, positive surgical margins, insignificant prostate cancer, and PSA outcomes were recorded. RESULTS: Median age was 63 years. Mean prebiopsy PSA level was 6.2 ng/mL. At radical prostatectomy, Gleason score was upgraded in 34% of patients, including 1.2% Gleason score 8-9. Pathologic stages were pT2 in 87.3%, pT3 in 11.1%, and pT4 in 1.4% of cases. Extraprostatic extension was found in 12.5%. Only 26% of patients had "insignificant" tumors. Biochemical recurrence-free survival at 5 years was 92.3%. There was no significant difference in survival between patients with "significant" and "insignificant" tumors (90.1% vs 93.4%; P = .06). CONCLUSION: Despite of a stringent selection of patients with low-risk prostate cancer, active surveillance definition included a significant proportion of patients with upstaged (about 12%) and upgraded (about one-third) disease at diagnosis. Only a quarter of active surveillance patients have a pathologically confirmed "insignificant" cancer.

Negative prostatic biopsies in patients with a high risk of prostate cancer. Is the combination of endorectal MRI and magnetic resonance spectroscopy imaging (MRSI) a useful tool? A preliminary study.

OBJECTIVE: Repeated biopsies in patients with a high risk of prostate cancer only allow a small proportion of new cancer diagnosis. The aim of this study was to evaluate the use of combined MRI and magnetic resonance spectroscopy imaging (MRSI) for these patients. METHODS: Between April 2003 and April 2004, 42 patients with negative multiple cores prostatic biopsies and serum PSA>4 ng/ml underwent a combined MRI/MRSI analysis. Suspicious zones on standard MRI included low intensity signals on T2 weighted images. A high choline+creatine-to-citrate ratio defined a MRSI suspicious zone. A 10 cores following peripheral biopsy scheme was done to which were added supplementary biopsies on the MRI/MRSI suspicious zones. RESULTS: The mean age was 62.3 years (51-74), the mean pre-biopsy serum PSA was 12 (3.87-35), the mean free/total PSA ratio was 11% (5-20). The mean number of previous prostate biopsy rounds was 2.04. 15 prostate cancers were diagnosed (35.7%). In 9 cases, abnormal MRI/MRSI findings and positive biopsy sites were located on the same prostatic zones. In 5 cases, MRSI alone located the positive biopsy zones. Sensitivity of combined MRI/MRSI in this study was 73.3%; specificity, positive predictive value, negative predictive value and accuracy were 96.3%, 91.6%, 86.6% and 88% respectively. CONCLUSIONS: This preliminary study shows that the combination of MRI and MRSI might be able to guide and therefore limit the number of iterative biopsies and cores for patients who are at high risk of having a prostate cancer. In some cases, MRSI alone allows identification of neoplasic prostatic zones. Other studies are needed to confirm these data.