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Pathology grading of prostate biopsy follows the rule that the highest International Society of Urological Pathology grade group (GG) is the GG assigned. This rule was developed in the systematic biopsy (SBx) era and makes sense when samples are from very different areas of the prostate. This rule has been kept for multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (MRI-TBx), for which multiple samples-targeted and systematic-are taken from small areas. In particular, if the results for SBx and MRI-TBx are discordant, the patient is assigned the higher GG. However, the most appropriate grading when MRI-TBx and SBx grades are discordant has never been investigated empirically. A cohort of patients who have undergone SBx and MRI-TBx with long oncological follow-up does not yet exist. To estimate the risk of recurrence for every combination of biopsy and pathological grades, we used the GG on radical prostatectomy (RP) as a surrogate for GG on MRI-TBx GG surrogate. We analyzed data for 12 468 men who underwent SBx and RP at a tertiary referral center and assessed 5-yr biochemical recurrence-free survival (bRFS) for each pairwise combination of biopsy and surgical GG results. We found that for cases with discordant SBx and RP grades, the risk of recurrence was intermediate, irrespective of whether the highest grade was at RP or SBx. For instance, the 5-yr bRFS rate was 57% for men with GG 3 on RP and 60% for men with GG 3 on SBx, but 63% for men with RP GG 3 and SBx GG 2, and 79% for men with RP GG 2 and SBx GG 3. Translating these findings to MRI-TBx casts doubt on current grading practice: when GGs are discordant between SBx and MRI-TBx, the risk of biochemical recurrence risk is not driven by the highest grade but by an intermediate between the two grades. Our findings should motivate studies assessing long-term outcomes for patients undergoing both MRI-TBx and SBx with a view to empirically evaluating current grading practices. PATIENT SUMMARY: Patients with prostate cancer may undergo two biopsy types: (1) systematic biopsy, for which sampling follows a systematic template; and (2) targeted biopsy, for which samples are taken from lesions detected on scans. There may be a difference in prostate cancer grade identified by the two approaches. In such cases, the risk of cancer recurrence seems to be predicted by an intermediate grade between the lower and higher grades., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Salvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown., Objective: To evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens., Design, Setting, and Participants: Men who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis., Outcome Measurements and Statistical Analysis: Primary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides., Results and Limitations: Of 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%-89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men., Conclusions: In men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In the eighth edition AJCC staging, all organ-confined disease is assigned pathologic stage T2, without subclassification. We investigated whether total tumor volume (TTV) and/or maximum tumor diameter (MTD) of the index lesion are useful in improving prediction of biochemical recurrence (BCR) in pT2 patients. We identified 1657 patients with digital tumor maps and quantification of TTV/MTD who had pT2 disease on radical prostatectomy (RP). Multivariable Cox regression models were used to assess whether TTV and/or MTD are independent predictors of BCR when adjusting for a base model incorporating age, preoperative prostate-specific antigen, RP grade group, and surgical margin status. If either tumor quantification added significantly, we calculated and reported the c-index. Ninety-five patients experienced BCR after RP; median follow-up for patients without BCR was 5.7 years. The c-index was 0.737 for the base model. Although there was some evidence of an association between TTV and BCR (P=0.088), this did not meet conventional levels of statistical significance and only provided a limited increase in discrimination (0.743; c-index improvement: 0.006). MTD was not associated with BCR (P>0.9). In analyses excluding patients with grade group 1 on biopsy who would be less likely to undergo RP in contemporary practice (622 patients; 59 with BCR), TTV/MTD was not a statistically significant predictor (P=0.4 and 0.8, respectively). Without evidence that tumor quantitation, in the form of either TTV or MTD of the index lesion, is useful for the prediction of BCR in pT2 prostate cancer, we cannot recommend its routine reporting.

Introduction: The use of multiparametric magnetic resonance imaging (mpMRI) to assess prostate cancer (PCa) has increased over the past decade. We aimed to assess if preoperative mpMRI lesion score, a variable routinely available for men undergoing pre-biopsy MRI, improves the performance of commonly used preoperative predictive models for PCa recurrence., Patients and Methods: We analyzed data from 372 patients with PCa treated with radical prostatectomy in 2012 to 2017 and assessed with pre-biopsy mpMRI within 6 months prior to surgery. Suspicious areas for cancer were scored on a standardized 5-point scale. Cox regression was used to assess the association between mpMRI score and the risk of postoperative biochemical recurrence. Two different models were tested accounting for factors included in the Kattan nomogram and in the D'Amico risk-classification., Results: Overall, 53% and 30% of patients were found with a lesion scored 4 or 5 at pre-biopsy mpMRI, respectively. Risk varied widely by mpMRI (29% 2-year risk of biochemical recurrence for a score of 5 vs. 5% for a score of 1-2), and mpMRI score was associated with large hazard ratios after adjusting for stage, grade, and prostate-specific antigen: 1.66, 1.96, and 2.71 for scores 3, 4, and 5, respectively. However, 95% confidence intervals were very wide (0.19-14.20, 0.26-14.65, and 0.36-20.55, respectively) and included 1., Conclusions: Our data did not show that preoperative models, commonly used to assess PCa risk, were improved after including the pre-biopsy mpMRI score. However, the value of pre-biopsy mpMRI to improve preoperative risk models should be investigated in larger data sets., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: We tested the latest update in the prostate cancer staging system by assessing the prognostic association of pT2 subclassification with the probability of survival related outcomes in patients who underwent radical prostatectomy., Materials and Methods: We retrospectively analyzed the records of a total of 15,305 patients who underwent radical prostatectomy at 2 referral centers between 1985 and 2016, and had pT2 disease at the final pathological evaluation. Descriptive statistics were used to compare baseline data stratified by pT2 substages (pT2a/b vs pT2c). Cox regression models were adjusted for institution analyzed differences in the rate of biochemical recurrence, metastasis, cancer specific death and overall mortality. Multivariable Cox regression models were used to evaluate the predictive value of pT2 subclassification for survival, including the linear predictor from the Stephenson nomogram., Results: Prostate specific antigen levels and Gleason score differed significantly between the pT2 substages (each p <0.0001). At a median followup of 6.0 years (IQR 3.3-10.1) 2,083 patients had biochemical recurrence, 161 had metastases, 43 had died of prostate cancer and 1,032 had died of another cause. On univariate analysis the pT2 subclassification was significantly associated with biochemical recurrence (p = 0.001) and distant metastasis (p = 0.033) but not with cancer specific death (p = 0.6) or overall mortality (p = 0.3). Multivariable analysis showed no evidence of a significant association between the pT2 subclassification and biochemical recurrence (p = 0.4) or distant metastasis (p = 0.6). Multivariable analysis of cancer specific death and overall mortality was omitted due to lack of significance on univariate analysis., Conclusions: Subclassification of pT2 prostate cancer is not a prognostic indicator of survival related outcomes after radical prostatectomy. Our results validate the elimination of pT2 substages in the updated staging system., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Presence of lymph node metástasis (LNM) at salvage radical prostatectomy (sRP) is associated with poor outcome. Predictors of outcome in this context remain undetermined. ThE objective was to assess the role of number of positive lymph node on outcome of patients with LNM after sRP and for radio-recurrent prostate cancer., Material and Methods: We analyzed data from a consecutive cohort of 215 men treated with sRP at a single institution. We used univariate Cox proportional hazard regression models for biochemical recurrence (BCR) and metastatic outcomes, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesicle invasion, time between radiation therapy and sRP, and number of positive nodes as predictors., Results: Of the 47 patients with LNM, 37 developed BCR, 11 developed distant metastasis and 4 died with a median follow-up of 2.3 years for survivors. The risk of metastases increased with higher pre-operative PSA levels (HR 1.19 per 1ng/ml; 95% CI: 1.06-1.34; P=.003). The remaining predictors did not reach conventional levels of significance. However, removal of 3 or more positive lymph nodes demonstrated a positive association, as expected, with metastatic disease (HR 3.44; 95% CI: 0.91-13.05; P=.069) compared to one or 2 positive nodes. Similarly, the presence of extraprostatic extension, seminal vesicle invasion and Gleason grade greater than 7 also demonstrated a positive association with higher risk of metástasis, with hazard ratios of 3.97 (95% CI: 0.50, 31.4; P=.2), 3.72 (95% CI: 0.80-17.26; P=.1), and 1.45 (95% CI: 0.44-4.76; P=.5), respectively., Conclusions: In patients with LNM after sRP for radio-recurrent prostate cancer, the risk of distant metástasis is likely to be influenced by the number of positive nodes (3 or more), high preoperative PSA, Gleason grade and advanced pathologic stage. These results are consistent with the findings of number of nodes (1 to 2 vs. 3 or more nodes positive) as a prognostic indicator after primary radical prostatectomy and strengthen the plea for a revision of the nodal staging for prostate cancer., (Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Limited data are currently available regarding the outcomes of radical prostatectomy (RP) in men with low-risk prostate cancer who were initially managed by active surveillance (AS)., Objective: To evaluate the pathologic outcomes of patients who underwent RP following initial AS., Design, Setting, and Participants: We analyzed the records of 67 patients who underwent RP following initial AS begun between 1993 and 2011. All patients underwent confirmatory biopsy to reassess eligibility for AS. RP was recommended for disease progression suggested by follow-up biopsies or imaging., Outcome Measurements and Statistical Analysis: Unfavorable disease was defined as having at least one of the following pathologic findings: Gleason score (GS) ≥4+3, extracapsular extension of tumor, seminal vesicle invasion, or lymph node involvement. A descriptive analysis was performed to assess pathologic features., Results and Limitations: Median time from confirmatory biopsy to RP was 1.7 yr (range: 0.3-7.8). Reasons for discontinuing AS to undergo RP included evidence of increased tumor volume or grade on follow-up biopsy, patient preference/anxiety, and findings on follow-up imaging in 46 patients (68.7%), 17 patients (25.3%), and 4 patients (6.0%), respectively. Pathologic analyses revealed organ-confined disease in 55 patients (82.1%), and GS was ≥4+3 in 9 (13.4%). Positive nodes were observed in three patients (4.4%) and positive surgical margin in two (3.0%). Overall, 19 patients (28.4%) had unfavorable disease. Of the biopsy criteria for triggering RP, Gleason patterns >3 were the most frequently associated with unfavorable disease (43.3%). One patient (1.5%) experienced biochemical recurrence during postoperative follow-up (median: 3.2 yr). Our study may be limited by its retrospective and single-institution nature., Conclusions: Most patients who started initially on AS after undergoing confirmatory biopsy showed pathologically organ-confined disease with a low GS at RP. Such findings provide further evidence that, overall, AS is a safe treatment approach., (Copyright © 2013. Published by Elsevier B.V.)

Objective: To compare early oncological outcomes of robot assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) performed by high volume surgeons in a contemporary cohort., Methods: We reviewed patients who underwent radical prostatectomy for prostate cancer by high volume surgeons performing RALP or ORP. Biochemical recurrence (BCR) was defined as PSA ≥ 0.1 ng/mL or PSA ≥ 0.05 ng/mL with receipt of additional therapy. A Cox regression model was used to evaluate the association between surgical approach and BCR using a predictive model (nomogram) based on preoperative stage, grade, volume of disease and PSA. To explore the impact of differences between surgeons, multivariable analyses were repeated using surgeon in place of approach., Results: Of 1454 patients included, 961 (66%) underwent ORP and 493 (34%) RALP and there were no important differences in cancer characteristics by group. Overall, 68% of patients met National Comprehensive Cancer Network (NCCN) criteria for intermediate or high risk disease and 9% had lymph node involvement. Positive margin rates were 15% for both open and robotic groups. In a multivariate model adjusting for preoperative risk there was no significant difference in BCR rates for RALP compared with ORP (hazard ratio 0.88; 95% CI 0.56-1.39; P = 0.6). The interaction term between nomogram risk and procedure type was not statistically significant. Using NCCN risk group as the covariate in a Cox model gave similar results (hazard ratio 0.74; 95% CI 0.47-1.17; P = 0.2). The interaction term between NCCN risk and procedure type was also non-significant. Differences in BCR rates between techniques (4.1% vs 3.3% adjusted risk at 2 years) were smaller than those between surgeons (2.5% to 4.8% adjusted risk at 2 years)., Conclusions: In this relatively high risk cohort of patients undergoing radical prostatectomy we found no evidence to suggest that ORP resulted in better early oncological outcomes then RALP. Oncological outcome after radical prostatectomy may be driven more by surgeon factors than surgical approach., (© 2013 The Authors BJU International © 2013 BJU International.)

Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes., Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response., Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07)., Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: With salvage radiation therapy (SRT) in the postprostatectomy setting, the need to deliver sufficient radiation doses to achieve a high probability of tumor control is balanced with the risk of increased toxicity. Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage setting is gaining interest as a treatment strategy., Objective: Compare acute and late toxicities in patients treated with IMRT and three-dimensional conformal radiation therapy (3D-CRT) in the postprostatectomy salvage setting., Design, Setting, and Participants: A total of 285 patients who were treated at our institution between 1988 and 2007 with SRT after radical prostatectomy for biochemical recurrence were identified. All medical records were reviewed and toxicity recorded. Median follow-up was 60 mo., Intervention: All patients were treated with SRT with either 3D-CRT (n=109) or IMRT (n=176). A total of 205 patients (72%) were treated with doses ≥70Gy., Measurements: Late gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the Common Terminology Criteria for Adverse Events v. 3.0 definition., Results and Limitations: The 5-yr actuarial rates of late grade ≥2 GI and GU toxicity were 5.2% and 17.0%, respectively. IMRT was independently associated with a reduction in grade ≥2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT, 10.2%; p=0.02). IMRT was not associated with a reduction in risk of grade ≥2 GU toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p=0.86), urinary incontinence (5-yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p=0.25), or grade 3 erectile dysfunction (5-yr IMRT, 26%; 5-yr 3D-CRT, 30%; p=0.82). Of patients who developed late grade ≥2 GI or GU toxicity, 38% and 44%, respectively, experienced resolution of their symptoms prior to the last follow-up., Conclusions: Our experience with high-dose IMRT in the postprostatectomy salvage setting demonstrates that the treatment can be delivered safely with an associated reduction in late GI toxicity., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Unlabelled: Study Type - Prognosis (case series)., Level of Evidence: 4. What's known on the subject? and What does the study add? The reported incidence of lymphovascular invasion (LVI) in radical prostatectomy specimens ranges from 5% to 53%. Although LVI has a strong and significant association with adverse clinicopathologic features, it has almost uniformly not been found to be a predictor of biochemical recurrence (BR) on multivariate analysis. This study confirms that LVI is associated with features of aggressive disease and is an independent predictor of BCR. Given that LVI may play a role in the metastatic process, it may be useful in clinical decision-making regarding adjuvant therapy for patients treated with RP., Objectives: To determine whether lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens has prognostic significance. The study examined whether LVI is associated with clinicopathological characteristics and biochemical recurrence (BCR)., Patients and Methods: LVI was evaluated based on routine pathology reports on 1298 patients treated with RP for clinically localized prostate cancer between 2004 and 2007. LVI was defined as the unequivocal presence of tumour cells within an endothelium-lined space. The association between LVI and clinicopathological features was assessed with univariate logistic regression. Cox regression was used to test the association between LVI and BCR., Results: LVI was identified in 10% (129/1298) of patients. The presence of LVI increased with advancing pathological stage: 2% (20/820) in pT2N0 patients, 16% (58/363) in pT3N0 patients and 17% (2/12) in pT4N0 patients; and was highest in patients with pN1 disease (52%; 49/94). Univariate analysis showed an association between LVI and higher preoperative prostate-specific antigen levels and Gleason scores, and a greater likelihood of extraprostatic extension, seminal vesicle invasion, lymph node metastasis and positive surgical margins (all P < 0.001). With a median follow-up of 27 months, LVI was significantly associated with an increased risk of BCR after RP on univariate (P < 0.001) and multivariate analysis (hazard ratio, 1.77; 95% confidence interval, 1.11-2.82; P = 0.017). As a result of the relatively short follow-up, the predictive accuracy of the standard clinicopathological features was high (concordance index, 0.880), and inclusion of LVI only marginally improved the predictive accuracy (0.884)., Conclusions: Although associated with features of aggressive disease and BCR, LVI added minimally to established predictors on short follow-up. Further study of cohorts with longer follow-up is warranted to help determine its prognostic significance., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Background: Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined., Objective: To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP., Design, Setting, and Participants: This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers., Intervention: Open SRP., Measurements: BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥ 0.1 or ≥ 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death., Results and Limitations: Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period., Conclusions: In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The prognostic significance of capsular incision (CapI) into tumor during radical prostatectomy (RP) with otherwise organ-confined disease remains uncertain., Objective: To evaluate the impact of CapI into tumor on oncologic outcome., Design, Setting, and Participants: A retrospective review of 8110 consecutive patients with prostate cancer treated at Ottawa Hospital and at Memorial Sloan-Kettering Cancer Center, both tertiary academic centers, between 1985 and 2008., Intervention: All patients underwent an open, laparoscopic or robotic RP., Measurements: Patients were divided into four pathologic categories: group 1 (CapI group), positive surgical margins (PSMs) without extraprostatic extension (EPE); group 2, negative surgical margins (NSMs) without EPE; group 3, NSM with EPE; group 4, PSMs with EPE. Estimates of recurrence-free survival were generated with the Kaplan-Meier method. Recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/ml and rising. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for recurrence controlling for pretreatment PSA, RP date, RP Gleason sum, seminal vesicle invasion, and lymph node involvement. Pathologic categories were defined in the model by including the variables EPE and surgical margins (SMs) as well as their interaction., Results and Limitations: Median follow-up was 37.3 mo. The 5-yr recurrence-free probability after RP for the CapI group was 77% (95% confidence interval [CI], 72-83). This was not only inferior to patients with NSMs and no EPE (log rank p<0.0001) but also to those with NSMs and EPE (log rank p=0.0002). In multivariate analysis the interaction between EPE and SM was not significant (p=0.26). In the adjusted model excluding the interaction term, patients with EPE had an increased risk for recurrence (HR: 1.80; 95% CI, 1.49-2.17; p<0.0001) as did those with positive margins (HR: 1.81; 95% CI, 1.51-2.15; p<0.0001). This was a retrospective study., Conclusions: CapI into tumor has a significant impact on patient outcome following RP. Patients, who otherwise would have organ-confined disease, will now have a higher probability of recurrence than those with completely resected extraprostatic disease., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine if the location and number of positive surgical margins (PSMs) after radical prostatectomy (RP) are associated with recurrence after salvage external beam radiation therapy (sEBRT)., Patients and Methods: We retrospectively reviewed the medical records of 60 patients with PSMs who underwent three-dimensional conformal sEBRT for biochemical recurrence (BCR) or clinically detected local recurrence after RP between 1996 and 2007. PSMs were categorized as present or absent at three locations, and patients were classified as having either one or more than one PSM. BCR after RP was defined as a prostate-specific antigen (PSA) level of ≥ 0.1 ng/mL. BCR after sEBRT was defined as a serum PSA level of ≥ 0.1 ng/mL above the PSA nadir after sEBRT., Results: In all, 24 (40%) patients had more than one PSM. Overall, the most common location of a PSM was the posterior prostate with 40 (66%) patients having a positive posterior margin. The location of PSMs was not significantly associated with secondary BCR (global P= 0.8). There was a borderline result between the number of PSMs and BCR: men with more than one PSM were less likely to recur compared with those with only one PSM (hazard ratio 0.42; P= 0.067)., Conclusions: This is the first study to specifically analyse location and number of PSMs as prognostic factors for men who undergo sEBRT. There was no evidence to suggest that the location of a PSM predicted secondary BCR. Further research is needed to determine whether the number of PSMs is an important predictor of BCR after sEBRT., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Purpose: Prostate cancer is a heterogeneous disease with a variable natural history that is not accurately predicted by currently used prognostic tools., Experimental Design: We genotyped 798 prostate cancer cases of Ashkenazi Jewish ancestry treated for localized prostate cancer between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to clinical data. The survival analysis was adjusted for Gleason score and prostate-specific antigen. We investigated associations between 29 single nucleotide polymorphisms (SNP) and biochemical recurrence, castration-resistant metastasis, and prostate cancer-specific survival. Subsequently, we did an independent analysis using a high-resolution panel of 13 SNPs., Results: On univariate analysis, two SNPs were associated (P<0.05) with biochemical recurrence, three SNPs were associated with clinical metastases, and one SNP was associated with prostate cancer-specific mortality. Applying a Bonferroni correction (P<0.0017), one association with biochemical recurrence (P=0.0007) was significant. Three SNPs showed associations on multivariable analysis, although not after correcting for multiple testing. The secondary analysis identified an additional association with prostate cancer-specific mortality in KLK3 (P<0.0005 by both univariate and multivariable analysis)., Conclusions: We identified associations between prostate cancer susceptibility SNPs and clinical end points. The rs61752561 in KLK3 and rs2735839 in the KLK2-KLK3 intergenic region were strongly associated with prostate cancer-specific survival, and rs10486567 in the 7JAZF1 gene were associated with biochemical recurrence. A larger study will be required to independently validate these findings and determine the role of these SNPs in prognostic models., (Copyright (c) 2010 AACR.)

Purpose: Positive surgical margins increase the risk of biochemical recurrence after radical prostatectomy by 2 to 4-fold. The risk of biochemical recurrence may be influenced by the anatomical location and extent of positive surgical margins. In a multicenter study we analyzed the predictive usefulness of several subclassifications of positive surgical margins., Materials and Methods: The clinical information and followup data of 7,160 patients treated with radical prostatectomy alone at 1 of 3 institutions between 1995 and 2006 were modeled using Cox proportional hazards regression analysis for biochemical recurrence. Positive surgical margins were analyzed as solitary vs multiple, focal vs extensive and apical location vs other. The usefulness of these subclassifications was assessed by the improvement in predictive accuracy of nomograms containing these parameters compared to one in which the surgical margin was modeled simply as positive vs negative., Results: The 7-year progression-free probability was 60% in patients with positive surgical margins. A positive surgical margin was significantly associated with biochemical recurrence (HR 2.3, p <0.001) after adjusting for age, prostate specific antigen, pathological Gleason score, pathological stage and year of surgery. An increased risk of biochemical recurrence was associated with multiple vs solitary positive surgical margins (adjusted HR 1.4, p = 0.002) and extensive vs focal positive surgical margins (adjusted HR 1.3, p = 0.004) on multivariable analysis. However, neither parameter improved the predictive accuracy of a nomogram compared to one in which surgical margin status was modeled as positive vs negative (concordance index 0.851 vs 0.850 vs 0.850)., Conclusions: The number and extent of positive surgical margin significantly influence the risk of biochemical recurrence after radical prostatectomy. However, the empirical prognostic usefulness of subclassifications of positive surgical margins is limited.

Objective: To determine the biochemical recurrence (BCR) rate in patients with positive surgical margins (PSMs) on the prostate specimen who have additional negative tissue resected from that site (M+ -), compared to patients with negative margins (M-) and those with persistent PSM (M+), as those with PSM at radical prostatectomy (RP) are at greater risk of BCR, and in some instances where suspicious tissue is noted in the prostate bed or when frozen-section analysis shows PSM, additional tissue is resected from the suspect site of the PSM., Patients and Methods: Between January 1999 and June 2007, 4217 consecutive patients underwent open or laparoscopic RP with no previous radiotherapy or hormonal therapy. The median (interquartile range) follow-up was 37.4 (21.1-60.7) months., Results: Pathological organ-confined (OC) cancer was present in 2901 men, of whom 2659 had M-, 216 had M+, and 26 had M+-. Extracapsular extension (ECE) alone with no seminal vesicle or lymph node involvement was present in 843 men, of whom 657 had M-, 174 had M+ and 12 had M+-. For patients with OC cancer, the 36-month actuarial BCR-free probability was 97.9% (95% confidence interval 97.3-98.5) for M-, vs 89.0 (84.1-93.9)% for M+ vs 100% for M+-. For patients with ECE, the 36-month actuarial BCR-free probability was 83.7 (80.0-87.4)% for M- vs 73.7 (66.1-81.3)% for M+ vs 90.0 (71.4-100)% for M+-. The main limitation of the study was its retrospective nature, with the reason for resection of additional tissue not always well documented., Conclusions: While the few patients with PSMs and further negative resected tissue limited the statistical analysis, it would appear that in these patients the disease behaves as in those with negative margins.

Objective: To investigate whether magnetic resonance imaging (MRI) findings, when converted into a scoring system, can predict the biochemical recurrence of prostate cancer after radical prostatectomy (RP)., Patients and Methods: Between January 2000 and October 2004, 610 patients with biopsy-confirmed prostate cancer had MRI before RP, with whole-mount step-sectioning of the pathology sample. MRI findings were retrospectively scored on a seven-point scale based on Tumour-Node-Mestastasis staging (1, no tumour seen, to 7, lymph node metastasis). MRI scores were added to published 5- and 10-year clinical preoperative nomograms for predicting recurrence. The predictive accuracy of MRI was quantified as the differences in bootstrap-corrected concordance indices of the models with and without MRI., Results: As of August 2007, 64 (10.5%) patients had a biochemical recurrence. MRI scores were associated with recurrence (P < 0.001) with hazard ratios of 1.76 and 1.81 in the 5- and 10-year models, respectively. Actual recurrence rates by MRI score were: 1, 0%; 2, 4.5%; 3, 9%; 4, 24.1%; 5, 33.3%; 6, 69.2%; 7, 100%. When MRI was added, the concordance indices of the 5- and 10-year models increased, from 0.762 to 0.776 (P = 0.081) and 0.773 to 0.788 (P = 0.107), respectively; the improvement was not significant., Conclusion: The MRI scoring system devised was a strong predictor of biochemical recurrence after RP. Although MRI did not provide added prognostic value to standard clinical nomograms, in centres where MRI is used routinely, it might increase the confidence of the clinician in assessing the risk of recurrence by contributing supporting data.

Purpose: Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model., Patients and Methods: The cohort included 2,938 patients with two or more PSA values before radical prostatectomy. Biochemical recurrence (BCR) occurred in 384 patients, and metastases occurred in 63 patients. Median follow-up for patients without BCR was 2.1 years. We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis. Predictive accuracy was assessed using the concordance index., Results: On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P < .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.

Background: Accurate preoperative and postoperative risk assessment has been critical for counseling patients regarding radical prostatectomy for clinically localized prostate cancer. In addition to other treatment modalities, neoadjuvant or adjuvant therapies have been considered. The growing literature suggested that the experience of the surgeon may affect the risk of prostate cancer recurrence. The purpose of this study was to develop and internally validate nomograms to predict the probability of recurrence, both preoperatively and postoperatively, with adjustment for standard parameters plus surgeon experience., Methods: The study cohort included 7,724 eligible prostate cancer patients treated with radical prostatectomy by 1 of 72 surgeons. For each patient, surgeon experience was coded as the total number of cases conducted by the surgeon before the patient's operation. Multivariable Cox proportional hazards regression models were developed to predict recurrence. Discrimination and calibration of the models was assessed following bootstrapping methods, and the models were presented as nomograms., Results: In this combined series, the 10-year probability of recurrence was 23.9%. The nomograms were quite discriminating (preoperative concordance index, 0.767; postoperative concordance index, 0.812). Calibration appeared to be very good for each. Surgeon experience seemed to have a quite modest effect, especially postoperatively., Conclusions: Nomograms have been developed that consider the surgeon's experience as a predictor. The tools appeared to predict reasonably well but were somewhat little improved with the addition of surgeon experience as a predictor variable., ((c) 2009 American Cancer Society.)

Background: Limited data on patterns of recurrence (local or metastatic) after salvage radical prostatectomy (SP) is available., Objective: To examine biochemical, local and metastatic patterns of recurrence in patients undergoing SP for radiation-recurrent prostate cancer., Design, Setting, and Participants: 146 patients with biopsy-proven local recurrence of prostate cancer after radiation therapy treated with SP were evaluated in a retrospective study at a single institution., Intervention: All patients underwent SP by mainly two surgeons., Measurements: Biochemical recurrence (BCR) after SP was defined as a serum prostate-specific antigen (PSA) level of >or=0.2 ng/ml or was defined by the initiation of androgen deprivation therapy. All predictors analyzed were determined after radiotherapy, before SP, and included PSA level, clinical stage, biopsy Gleason score, age at SP, and time interval from radiotherapy to SP., Results and Limitations: Of the 146 patients treated with SP, 65 developed BCR. The median follow-up period for recurrence-free patients was 3.8 yr; 43 patients (29%) were followed for >5 yr. Overall, the 5-yr recurrence-free probability was 54% (95% CI, 44-63%). Clinical local recurrence occurred in only one patient who also had bone metastases. Overall, there were 16 prostate cancer-specific deaths and 19 deaths from other causes. The 5-yr cumulative incidence of death from prostate cancer was 4% (95% CI, 2-11%). Pre-SP serum PSA level and biopsy Gleason score were significantly associated with death due to prostate cancer (p<0.0005 and p=0.002, respectively). This study is retrospective and included carefully selected patients treated over a long period by, mainly, two experienced surgeons., Conclusions: SP provides excellent local cancer control; only one patient in our series experienced a clinical local recurrence. Earlier identification of patients with persistent, viable local cancer despite radiation therapy will appropriately select patients for SP.

Purpose: Standardized criteria are lacking to define high risk, clinically localized prostate cancer before definitive treatment. Reliance on simple risk stratification schemes to define high risk cancers has led many physicians and patients toward therapeutic nihilism, inappropriately selecting androgen deprivation instead of definitive local therapy. Of patients undergoing radical prostatectomy we identified those at high risk based on 8 previously described definitions. We examined pathological characteristics and prostate specific antigen outcomes., Materials and Methods: The study population included 4,708 men treated with radical prostatectomy alone between 1985 and 2004. Estimates of prostate specific antigen relapse for patients at high risk were generated with the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the HR for recurrence in high risk vs nonhigh risk cohorts., Results: Depending on the definition used patients at high risk composed 3% to 38% of the study population. The proportion of patients with extracapsular extension, seminal vesicle invasion and lymph node metastasis among men with high risk cancer was 35% to 71%, 10% to 33% and 7% to 23%, respectively. Of the high risk tumors 22% to 63% proved to be confined to the prostate pathologically. While patients at high risk had a 1.8 to 4.8-fold increased hazard of prostate specific antigen relapse, their 5-year relapse-free probability after radical prostatectomy alone was 49% (95% CI 39 to 58) to 80% (95% CI 77 to 83). Of patients at high risk who had relapse 25% across all definitions experienced relapse more than 2 years after surgery and in 26% to 39% prostate specific antigen doubling time at recurrence was 10 months or greater., Conclusions: Patients diagnosed with high risk cancer by currently available definitions do not have a uniformly poor prognosis after radical prostatectomy. Many cancers classified clinically as high risk are actually confined to the prostate pathologically. The risk of extraprostatic disease and prostate specific antigen relapse varies greatly depending on the definition used.

Background: The learning curve for surgery--i.e., improvement in surgical outcomes with increasing surgeon experience--remains primarily a theoretical concept; actual curves based on surgical outcome data are rarely presented. We analyzed the surgical learning curve for prostate cancer recurrence after radical prostatectomy., Methods: The study cohort included 7765 prostate cancer patients who were treated with radical prostatectomy by one of 72 surgeons at four major US academic medical centers between 1987 and 2003. For each patient, surgeon experience was coded as the total number of radical prostatectomies performed by the surgeon before the patient's operation. Multivariable survival-time regression models were used to evaluate the association between surgeon experience and prostate cancer recurrence, defined as a serum prostate-specific antigen (PSA) of more than 0.4 ng/mL followed by a subsequent higher PSA level (i.e., biochemical recurrence), with adjustment for established clinical and tumor characteristics. All P values are two-sided., Results: The learning curve for prostate cancer recurrence after radical prostatectomy was steep and did not start to plateau until a surgeon had completed approximately 250 prior operations. The predicted probabilities of recurrence at 5 years were 17.9% (95% confidence interval [CI] = 12.1% to 25.6%) for patients treated by surgeons with 10 prior operations and 10.7% (95% CI = 7.1% to 15.9%) for patients treated by surgeons with 250 prior operations (difference = 7.2%, 95% CI = 4.6% to 10.1%; P<.001). This finding was robust to sensitivity analysis; in particular, the results were unaffected if we restricted the sample to patients treated after 1995, when stage migration related to the advent of PSA screening appeared largely complete., Conclusions: As a surgeon's experience increases, cancer control after radical prostatectomy improves, presumably because of improved surgical technique. Further research is needed to examine the specific techniques used by experienced surgeons that are associated with improved outcomes.

A significant number of men with prostate cancer will experience biochemical failure following treatment with primary radiation therapy. For patients with biopsy-proven recurrent cancer confined to the prostate, local salvage therapy may be a potentially curative treatment option. Most men, however, do not undergo local salvage therapy owing to difficulties in diagnosis as well as concerns over treatment-related complications in the salvage setting. Recently, improvements in technique and technology have substantially reduced the morbidity associated with locally ablative therapies, resulting in an increased interest in the use of minimally invasive therapies such as brachytherapy, cryotherapy, and high-intensity focused ultrasound in the salvage setting. Although these treatments are well tolerated, concerns remain over incomplete and inadequate treatment with locally ablative therapies. Future studies are required to appropriately select candidates for salvage ablative therapies and to determine the long-term oncologic efficacy of these treatments.

Purpose: Recurrent or radioresistant prostate cancer occurs in approximately 30% of men receiving primary radiotherapy. For men who are candidates for local salvage therapy, the oncological efficacy of ablative therapies may be affected by the anatomical and pathological features of cancers within irradiated prostate glands. We characterized and mapped the prostate cancers in our series of whole mount salvage radical prostatectomy specimens., Materials and Methods: A total of 47 salvage radical prostatectomies were performed at our institution between 2000 and 2004. Detailed pathological data, including the anatomical distribution of cancers, were obtained from 46 whole mount salvage radical prostatectomy specimens., Results: A total of 70 cancer foci were identified in 46 specimens. Of the specimens 93% had cancer foci at the apex. The median minimum cancer-to-urethra distance was smallest at the apex (4.1 mm) and greatest at the base (13.8 mm). More than 65% of patients had cancer 5 mm or less from the urethra and 7% of patients had cancer directly involving the urethra. Nearly half of all patients had evidence of extraprostatic disease., Conclusions: The anatomical and pathological features in our study demonstrate that a significant portion of irradiated cancers are pathologically advanced and distributed in regions of the prostate (apical and periurethral) which are at risk for undertreatment using current ablative therapies. Our findings raise serious concerns regarding the oncological efficacy of such treatment modalities. Long-term studies without the use of hormonal therapy are needed to determine the oncological efficacy of salvage ablative therapies in patients with radiorecurrent or resistant prostate cancer.

Purpose: Prostate-specific antigen (PSA) defined biochemical recurrence (BCR) of prostate cancer is widely used for reporting the outcome of radical prostatectomy (RP). A standardized BCR definition is lacking, and overall progression-free probability and risk of subsequent metastatic disease progression may vary greatly depending on the PSA criterion used. Ten definitions of BCR were evaluated to identify the one that best explains metastatic progression., Methods: Of 3,125 patients who underwent RP at our institution since 1985, 75 developed distant metastasis during a median follow-up of 49 months. To predict metastasis progression, we modeled the clinical information using multivariable Cox regression analysis. BCR was included in the model as a time-dependent covariate, and separate models were developed for each definition. A goodness-of-fit (R2) statistic was used to determine the Cox model (and thereby the BCR definition) that best explained metastatic progression., Results: The 10-year progression-free probability ranged from 63% to 79%, depending on the BCR definition. The model containing BCR defined as a PSA of at least 0.4 ng/mL followed by another increase best explained metastatic progression (R2 = 0.21). This definition was also associated with a high probability of subsequent secondary therapy, continued PSA progression, and rapid PSA doubling time., Conclusion: BCR defined as a PSA value of at least 0.4 ng/mL followed by another increase best explains the development of distant metastasis among 10 candidate definitions, after controlling for clinical variables and the use of secondary therapy. On the basis of this evidence, we propose that this definition be adopted as the standard for reporting the outcome of RP.

Background: The objectives of the current study were to determine the long-term biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate-specific antigen era and who had SVI identified at the time of radical prostatectomy (RP)., Methods: Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS., Results: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10-year and 15-year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10-year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate-specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS., Conclusions: SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good., (Copyright (c) 2006 American Cancer Society.)

Purpose: We investigated whether repeat prostate biopsies are associated with more favorable prognoses, less extensive disease or higher rates of IC in patients who are ultimately diagnosed with prostate cancer and treated with RRP., Materials and Methods: We examined standard clinical and pathological data on 1,357 patients treated with RRP from 1983 to 2001. In addition, we noted the rate of IC in a subgroup of 847 patients in whom tumor volume was measured., Results: Cancer was found in 1,042 patients (77%) at the first biopsy, in 227 (17%) at the second biopsy, in 59 (4%) at the third biopsy and in 29 (2%) at the fourth or later biopsy. Patients with 2 or greater biopsies had a higher rate of clinical T1c stage cancer and larger prostates than patients with only 1 biopsy (each p < 0.0001). After RRP patients with 1 biopsy had a lower rate of organ confined tumors (61% vs 75%, p < 0.0001), and a higher rate of extracapsular extension, seminal vesicle invasion, lymph node metastases and Gleason sum 7 or greater than other patients. IC was found in 10% of patients with 1 biopsy and 18% of those with 2 or greater biopsies (p = 0.018). Despite these more favorable pathological outcomes there was no difference in biochemical recurrence rate., Conclusions: Although we found that a greater number of biopsies was related to a better pathological outcome after RRP, the number of biopsies did not predict disease recurrence. The increasing number of biopsies currently being performed, especially in patients with larger prostates, likely results in higher rates of IC.

Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate-specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate-specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this "base" model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA < or = 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA < or = 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap-corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA-elevation (tPSA < or = 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756-0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for "moderately elevated" PSA. For patients with a moderate tPSA-elevation (tPSA < or = 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR-prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR., ((c) 2005 Wiley-Liss, Inc.)

Background: Men diagnosed with clinically localized prostate carcinoma have several treatment options. The investigation of these options may delay the initiation of definitive therapy. In the current study, the authors evaluated whether time from biopsy to radical prostatectomy (RP) was predictive of postoperative biochemical disease recurrence (BCR)., Methods: A total of 3149 consecutive patients who underwent RP as their initial treatment for prostate carcinoma within a year of diagnosis were identified. The time between diagnosis and RP was entered as a predictor in a multivariate logistic regression model predicting BCR at 3 years, 5 years, 8 years, and 10 years. The year surgery was performed and the nomogram-predicted probability of recurrence, which incorporates stage of disease, Gleason grade, and prostate-specific antigen (PSA) level, were used as covariates., Results: The authors found no clear evidence of a significant effect of delay to diagnosis on BCR. For those patients treated within 6 months (96% of the total sample) the odds ratio for each additional month of delay was 1.04, 1.07, 1.08, and 1.02, respectively, for 3-year, 5-year, 8-year, and 10-year BCR-free survival (P>0.2 for all analyses). However, the 95% confidence intervals were wide and included the possibility that even a minor delay in surgery might have a large impact on the probability of BCR., Conclusions: The time between biopsy and surgery does not appear to have a large effect on the risk of disease recurrence. Counseling patients on the importance of avoiding undue delay to surgery must be based on clinical judgment, particularly with respect to modifying advice based on the patient's risk., (Copyright (c) 2005 American Cancer Society.)

Patients with isolated local recurrence of prostate cancer after radiation therapy may potentially be cured of their disease by salvage radical prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP resemble those of standard RP. However, the ability to effectively administer salvage treatment to patients with radiorecurrent disease is compromised by the lack of diagnostic tests with sufficient sensitivity and specificity to detect local recurrence at an early stage while it is amenable to local salvage therapy. By the time biochemical recurrence is declared using the current American Society for Therapeutic Radiology and Oncology definition, the majority of patients have advanced local disease, precluding successful local salvage therapy. When salvage RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an estimated 70% of patients are free of disease at 5 years. With better patient selection and technical modifications, the morbidity associated with salvage RP has improved substantially. Rates of urinary incontinence and anastomotic stricture are acceptable, although one third of patients will experience these complications. Salvage cryotherapy is a minimally invasive alternative to salvage RP, but cancer-control rates appear to be inferior and it does not provide a clear advantage over salvage RP in terms of reduced morbidity. Patients with local recurrence after radiation therapy are at increased risk of metastatic progression and cancer-specific mortality. Currently, salvage RP represents the only curative treatment option for these patients. Salvage RP may favorably alter the natural history of biochemical recurrence after radiation therapy, but it must be instituted early in the course of recurrent disease to be effective.

Objective: To evaluate whether the time from biopsy to radical prostatectomy (RP) predicts the biochemical recurrence (BCR) after RP, as men diagnosed with clinically localized prostate cancer have several available treatment options and investigating these alternatives may delay the initiation of definitive therapy., Patients and Methods: We identified 3969 consecutive patients who had RP for clinically localized prostate cancer from 1987 to 2002; those eligible for the study had RP within a year of diagnosis. The interval between biopsy and RP was analysed both as a continuous and as a dichotomous variable (divided at 3 months). Multivariate analysis was used to evaluate the impact of time to RP on BCR. Subsets were also analysed for the effect of time to RP in patients considered to be at high risk of recurrence, with group 1 having a prostate specific antigen (PSA) level of > or = 20 ng/mL, a biopsy Gleason score of > or = 8, or clinical stage > or = T2c; and group 2 assessed as having a >40% probability of BCR using a preoperative nomogram., Results: In all, 3149 patients met the inclusion criteria and had a mean (interquartile range) follow-up after RP of 5.4 (2.2-7.9) years. Multivariate analysis showed that the year of biopsy, PSA level before biopsy, clinical stage and biopsy Gleason score (all P < 0.001) were significantly associated with BCR after RP. The time to RP, treated either as a continuous variable (P = 0.252) or when categorized at 3 months (P = 0.939), failed to predict BCR. Further, the time to RP was not an independent predictor of BCR for patients at high risk of recurrence in group 1 (P = 0.147) or group 2 (P = 0.548)., Conclusions: The time from biopsy to RP did not influence the probability of BCR for men who had RP within a year of diagnosis, even for those considered to be at high risk of BCR. Instead, the clinical and pathological features of the cancer provided the best estimate of the risk of BCR.

Purpose: A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP., Methods: Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy., Results: The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model included PSA (P = .002), primary (P < .0001) and secondary Gleason grade (P = .0006), extracapsular extension (P < .0001), positive surgical margins (P = .028), seminal vesicle invasion (P < .0001), lymph node involvement (P = .030), treatment year (P = .008), and adjuvant radiotherapy (P = .046). The concordance index of the nomogram when applied to the independent validation sets was 0.81 and 0.79., Conclusion: We have developed and validated as a robust predictive model an enhanced postoperative nomogram for prostate cancer recurrence after RP. Unique to predictive models, the nomogram predictions can be adjusted for the disease-free interval that a patient has achieved after RP.

Objectives: To analyze the feasibility of neurovascular bundle (NVB) preservation and peripheral nerve grafting during salvage radical prostatectomy (RP) for radiorecurrent prostate cancer and analyze their effect on the recovery of potency., Methods: Of 100 patients who underwent salvage RP with curative intent from 1984 to 2003, 7 patients had bilateral NVBs preserved, 22 had a unilateral NVB preserved with (n = 11) and without (n = 11) a unilateral nerve graft, and 9 had bilateral NVBs resected with bilateral nerve grafts. Preoperative erections were graded as normal (grade 1) in 12 patients and full but recently diminished (grade 2) in 16. Recovery of potency after salvage RP was defined as erections satisfactory for intercourse, with or without the use of sildenafil., Results: Overall, 6 patients recovered potency after salvage RP, and the 5-year actuarial recovery rate was 16% (95% confidence interval 4% to 28%). The 6 patients who recovered erections all had preoperative grade 1 to 2 erections, and 5 had bilateral NVBs preserved. Only 1 of 11 patients who had a unilateral nerve graft recovered potency. No patient with bilateral nerve grafts recovered potency. The 5-year actuarial recovery rate among patients with preoperative grade 1 to 2 erections was 45% (95% confidence interval 16% to 75%)., Conclusions: Compared with standard RP, the overall potency results after salvage RP are poor. However, select patients with good preoperative erectile function who have bilateral NVB preservation may recover erections sufficient for intercourse aided by sildenafil. Peripheral nerve grafts did not appear to influence the recovery of erections in this patient population.

Purpose: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival., Methods and Materials: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years)., Results: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression., Conclusions: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.

Purpose: Few patients with locally recurrent prostate cancer after external beam (EB) or interstitial (I) radiotherapy (RT) are considered candidates for salvage radical prostatectomy (RP) due to high reported rates of major complications and urinary incontinence. We report the morbidity associated with salvage RP in 100 consecutive patients., Materials and Methods: From 1984 to 2003 salvage RP was performed for recurrent prostate cancer following EBRT in 58 cases, and IRT in 42 (28 retropubic) and (14 transperineal). Clinical information was obtained from a prospective database., Results: Since 1993, the major complication rate has decreased significantly (13% vs 33%, p = 0.02), including the rectal injury rate (2% vs 15%, p = 0.01). Compared with retropubic IRT and/or pre-radiotherapy pelvic lymph node dissection the risk of major complications following EBRT or transperineal IRT was significantly less (OR 0.2, p = 0.006). At 5 years an estimated 39% of patients were dry and 68% required 1 pad daily or less. A total of 23 patients with moderate-severe incontinence underwent artificial sphincter placement. The anastomotic stricture rate was 30%. The 5-year potency rate was 28% following unilateral or bilateral nerve sparing RP and 45% in previously potent patients., Conclusions: Due to patient selection the major complication rate after salvage RP has improved significantly with time and it is similar to that of standard RP. Rates of anastomotic stricture and moderate to severe incontinence are higher than those observed after standard RP. However, most patients recover reasonable urinary continence and a substantial number of select patients recover potency. The acceptable morbidity profile of salvage RP following EBRT and transperineal IRT should persuade more physicians to consider patients for this potentially curative procedure.

The greatest obstacle in the cure of patients with locally recurrent prostate cancer after radiation therapy is the lack of early detection markers. The majority of patients who are candidates for local salvage therapy have locally advanced disease, precluding successful salvage therapy. A low pretreatment prostate specific antigen (PSA) has shown to be a favorable prognostic variable for disease progression, regardless of the specific local salvage therapy used. Of all the local salvage treatment options for these patients, we believe that salvage radical prostatectomy (RP) offers patients the greatest likelihood of a cure. The salvage RP results approach those achieved with standard RP for patients of similar pathologic stage. When patients are treated early in the course of recurrent disease (preoperative PSA < 10 ng/mL), an estimated two-thirds of patients will be disease-free 5 years after salvage RP alone. With better patient selection and continued technical modifications, the morbidity associated with salvage RP has substantially improved. Perioperative complications approach those observed with standard RP and approximately two-thirds of patients will recover urinary continence. Select patients may also recover functional erections when nerve-sparing techniques are used. Salvage cryotherapy and brachytherapy are minimally invasive alternatives to salvage RP. The cancer control results of these procedures appear to be inferior to results achieved with salvage RP. Each of these procedures is associated with significant morbidity and do not appear to provide a clear advantage over salvage RP in terms of posttreatment complications, urinary continence, and erectile function. A long-term cure is possible for patients with locally recurrent prostate cancer after radiation therapy. Local salvage therapy must be instituted early to be successful in the course of progressive disease.

The goal of primary radiation therapy in the treatment of prostate cancer is to eradicate all of the local tumor. Although patients with relapsing disease after radiation therapy differ in their risk of death from prostate cancer, many will develop local progression, metastasis, and death. The recognition that local recurrence after radiation therapy portends a poor prognosis has led to the development of improved methods for early detection of recurrence and the development of alternative treatment strategies for radioresistant cancers. This article reviews knowledge regarding radiation failure and the role of salvage radical prostatectomy for men with local recurrence after radiation therapy for prostate cancer.

Background: Squamous cell carcinoma of the penis is a rare malignancy in the United States, accounting for only 0.4% of all cancers in men., Methods: From June 1975 to June 2000, 45 patients were diagnosed and treated for squamous cell carcinoma of the penis at our institution. Their medical records were reviewed retrospectively., Results: The mean age at diagnosis was 63 years; 62% were white and 38% African American. Eighty-nine percent of our population was uncircumcised. Twenty patients had primary ilioinguinal lymph node dissections, with 11 positive for squamous cell carcinoma. Follow-up was documented for 42 patients, with a mean of 47 months. Four patients had local penile recurrence at a mean of 22 months after initial treatment. Nine patients had died of penile carcinoma at a mean of 18 months., Conclusion: Squamous cell carcinoma of the penis accounts for 0.3% of malignancies in men seen at our institution. Nodal metastasis was a poor prognostic indicator. Although local penile recurrence was rare (8.8%), patients should be counseled on the importance of self-examination.

Background: Although rare, renal cell carcinoma has been found during renal recovery for cadaveric organ transplantation. Previously, we reported this incidence to be 0.9%. In one cadaveric donor, the liver and left kidney had been transplanted before the discovery of renal cell carcinoma (T1) in the right kidney., Methods: We retrospectively reviewed the medical records of two patients who had received cadaveric allografts from a donor with a known renal cell carcinoma., Results: Both patients have been followed for 4 years with blood chemistries and chest x-ray every 3 months for year 1, every 4 months for years 2 and 3, and every 6 months thereafter. They also underwent allograft ultrasound every 6 months and an annual CT scan of the abdomen. Both patients have shown no evidence of metastatic disease throughout their follow-up., Discussion: In the rare instance that a patient receives an organ from a cadaveric donor with a known renal cell carcinoma, it is mandatory to follow these patients closely observing for both allograft recurrence and metastatic disease.

Purpose: The reported incidence and mortality of prostate cancer are higher among black than white men. Reasons for the disproportionate racial incidence of this disease are not known but most surveys suggest that increased mortality among black men is due to more advanced tumor stage at diagnosis. To determine if racial differences exist in men with similar stage disease we compared disease recurrence in black and white men who underwent radical prostatectomy for clinical stage T1-T2 prostate cancer., Materials and Methods: We reviewed the records of all 257 white and 218 black men undergoing radical prostatectomy for clinical stage T1-T2 prostate cancer at the Louisiana State University Medical Center-Shreveport and the Overton-Brooks Veterans Affairs Medical Center between January 1990 and November 1998. Age, race, serum prostate specific antigen (PSA), ultrasound measured prostate volume, PSA density (PSA divided by prostate volume), histological features of the prostate biopsy, clinical stage, pathological stage, histological features of the radical prostatectomy specimen and disease recurrence were reviewed., Results: Black men had significantly higher mean serum PSA and PSA density than white men (2-sided p = 0.005 and 0.03, respectively). There were no statistically significant differences by race in terms of patient age, prostate volume, clinical stage, biopsy Gleason score, pathological stage, positive pelvic lymph nodes, positive surgical margins or PSA recurrence rates., Conclusions: Black men with clinical stage T1-T2 prostate cancer who underwent radical prostatectomy had significantly higher serum PSA and PSA density than similarly treated white men. However, race appears to have no independent impact on pathological findings or disease recurrence in men with clinically localized prostate cancer treated with radical prostatectomy when the effects of differences in serum PSA are controlled.

Objectives: To determine whether race is an independent predictor of positive surgical margins in patients who undergo radical prostatectomy., Methods: Radical prostatectomies were performed on 750 patients at five Veterans Affairs hospitals: Shreveport, Louisiana (n = 451), Houston, Texas (n = 92), Jackson, Mississippi (n = 83), New Orleans, Louisiana (n = 69), and Little Rock, Arkansas (n = 55). All men who did not receive neoadjuvant hormonal therapy and for whom complete follow-up data were available were included in the analysis (of 607, 260 were African-American and 347 were white). Multiple logistic regression analysis was used to determine the significance of race as an independent predictor of surgical margin status after radical prostatectomy for clinically localized prostate cancer., Results: After controlling for clinical stage, Gleason grade, and preoperative prostate-specific antigen (PSA), multivariable logistic regression analysis revealed that race was not an independent predictor of positive surgical margins (P = 0.9). Of the variables evaluated, both preoperative PSA (P = 0.0005) and biopsy Gleason grade (P = 0.047) were significant predictors of an increased risk of a positive surgical margin., Conclusions: Positive surgical margins are a widely accepted surrogate marker of increased biologic potential in patients with prostate cancer. In our study population, race was not an independent predictor of surgical margin status. Coupled with observations that survival is not related to race, this finding suggests that the biology of prostate cancer in African-American and white men is similar and that observed racial differences more likely are due to ethnic factors that influence tumorigenicity.