[Radical prostatectomy in the treatment of organ confined prostate cancer]

Open radical prostatectomy represents one possible therapeutic option for treating patients with clinically localized prostate cancer Patient selection and the surgical management have undergone important changes during the last years, resulting in lower morbidity and probably in a better tumor control due to a better standardisation of the surgical technique. Long-term functional outcome regarding continence and potency are of increasing importance and influence mainly the quality of life in these patients. Open radical retropubic prostatectomy remains the gold standard in patients with localized prostate cancer, due to its low morbidity and excellent oncological and functional results. The value of laparoscopic and robotic radical prostatectomy is still discussed controversially. Due to the relative high morbidity during the so-called learning curve and the lack of long-term oncological and functional results, these techniques seem to show less favourable results.

Good outcome for patients with few lymph node metastases after radical retropubic prostatectomy

BACKGROUND: Conflicting results exist regarding the value of an extended pelvic lymph node dissection (PLND) in node-positive patients undergoing radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. OBJECTIVE: To assess the long-term outcome in node-positive patients who underwent extended PLND followed by RRP. DESIGN, SETTING, AND PARTICIPANTS: A consecutive series of 122 node positive patients with negative preoperative staging examinations, no neoadjuvant hormonal or radiotherapy, and who underwent extended PLND (>/=10 lymph nodes in the surgical specimen) followed by RRP were analyzed. None of the patients received immediate androgen deprivation therapy (ADT). INTERVENTION: All patients underwent extended PLND followed by RRP. MEASUREMENTS: Biochemical recurrence-free survival, cancer-specific, and overall survival were assessed using the Kaplan-Meier technique. RESULTS AND LIMITATIONS: Median prostate-specific antigen (PSA) was 16ng/ml. At pathological examination 76% of the 122 patients had pT3-pT4 tumours, 50% seminal vesicle infiltration. A median of 22 nodes were removed per patient. Median cancer-specific survival at 5 and 10 yr was 84.5% and 60.1%, respectively. In patients with /=3 positive nodes removed, median cancer-specific survival at 10 yr was 78.6% and 33.4%, respectively (p<0.001). After a median period of 33 mo, 61 of the 122 patients (50%) received ADT, particularly those (69%) with >/=3 positive nodes removed. This retrospective study includes a significant percentage of patients with high tumour burden, and therefore may not reflect current patient series. CONCLUSIONS: Patients with /=3 positive nodes, despite extended PLND and despite ADT in 69% of patients.

Removal of Limited Nodal Disease in Patients Undergoing Radical Prostatectomy: Long-Term Results Confirm a Chance for Cure

Abstract PURPOSE: In 2003 we reported on the outcomes of 88 patients with node positive disease who underwent radical prostatectomy and pelvic lymph node dissection (median 21 nodes) between 1989 and 1999. Patients with limited nodal disease appeared to have a good chance of long-term survival, even without immediate adjuvant therapy (androgen deprivation therapy and/or radiotherapy). In this study we update the followup in these patients and verify the reported projected probability of survival. MATERIALS AND METHODS: The projected 10-year cancer specific survival probability after the initially reported followup of 3.2 years was 60% for these patients with node positive disease. The outcome has been updated after a median followup of 15.6 years. RESULTS: Of the 39 patients with 1 positive node 7 (18%) remained biochemically relapse-free, 11 (28%) showed biochemical relapse only and 21 (54%) experienced clinical progression. Of these 39 patients 22 (57%) never required deferred androgen deprivation therapy and 12 (31%) died of prostate cancer. All patients with 2 (20) or more than 2 (29) positive nodes experienced biochemical relapse and only 5 (10%) of these 49 experienced no clinical progression. Of these 49 patients 39 (80%) received deferred androgen deprivation therapy. CONCLUSIONS: Biochemical relapse is likely in patients with limited nodal disease after radical prostatectomy and pelvic lymph node dissection, but for 47% of patients this does not imply death from prostate cancer. Patients with 1 positive node have a good (75%) 10-year cancer specific survival probability and a 20% chance of remaining biochemical relapse-free even without immediate adjuvant therapy.

Local recurrence after retropubic radical prostatectomy for prostate cancer does not exclusively occur at the anastomotic site

What's known on the subject? and What does the study add? Local recurrence after radical prostatectomy (RP) for clinically organ-confined prostate cancer is largely assumed to occur at the anastomotic site, as reflected in European and North American guidelines for adjuvant and salvage radiotherapy after RP. However, the exact site of local recurrence often remains undetermined. The present study shows that roughly one out of five patients with local recurrence after RP has histologically confirmed tumour deposits at the resection site of the vas deferens, clearly above the anastomotic site. This should be considered when offering ‘blind’ radiotherapy to the anastomotic site in patients with biochemical recurrence alone. Objective To determine the anatomical pattern of local recurrence and the corresponding clinical and pathological variables of patients treated with retropubic radical prostatectomy (RRP). Patients and Methods In all, 41 patients with biopsy confirmed local recurrence after extended pelvic lymph node dissection and RRP performed between January 1992 and December 2009 at a single tertiary referral academic centre were retrospectively studied. The site of local recurrence as assessed on computed tomography or magnetic resonance imaging was reviewed. Two sites were identified: the vesicourethral anastomotic site and the cranial resection margin of the surgical bed, where the vas deferens was transected and clipped. Age and serum prostate-specific antigen (PSA) level at RRP, pathological tumour and nodal stage, Gleason score, tumour location, surgical margin status, age and serum PSA level at the time of local recurrence, and time to diagnosis of local recurrence were assessed for the two sites and compared with the chi-square or Wilcoxon rank sum tests as appropriate. Results Local recurrence occurred at the anastomotic site in 31/41 (76%) patients and at the resection site of the vas deferens in nine of 41 (22%) patients. One patient had distinct lesions at both sites. There was no significant difference in any of the clinical and pathological variables between patients with local recurrence in the former and latter site. Conclusion Most local recurrences after RRP occur exclusively at the anastomotic site. However, 22% of locally recurrent cases had tumour at the resection site of the vas deferens. This should be taken into account when considering adjuvant or salvage radiation therapy.

Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer

Background A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. Methods In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. Results The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001). Conclusions General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

Salvage Radiotherapy After Radical Prostatectomy

Salvage radiation therapy is the sole curative treatment for patients experiencing biochemical relapse after radical surgical treatment of prostate cancer. The main dilemma in salvage radiation therapy is, whether or not biochemical relapse represents purely localized recurrent disease in the prostatic fossa or systemic micrometastasis. Initiating salvage radiation therapy at an early time point raises its chances of success, but may lead to overtreatment of patients. Target volume definition and treatment techniques are a matter of current research, with still many questions unanswered. Strategies of treatment escalation either by increasing the treatment dose or combining radiation therapy with androgen deprivation therapy are being addressed in clinical trials.

Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial.

BACKGROUND The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. METHODS This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. RESULTS Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. CONCLUSIONS In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

Ceramic foam plates: a new tool for processing fresh radical prostatectomy specimens

Procurement of fresh tissue of prostate cancer is critical for biobanking and generation of xenograft models as an important preclinical step towards new therapeutic strategies in advanced prostate cancer. However, handling of fresh radical prostatectomy specimens has been notoriously challenging given the distinctive physical properties of prostate tissue and the difficulty to identify cancer foci on gross examination. Here, we have developed a novel approach using ceramic foam plates for processing freshly cut whole mount sections from radical prostatectomy specimens without compromising further diagnostic assessment. Forty-nine radical prostatectomy specimens were processed and sectioned from the apex to the base in whole mount slices. Putative carcinoma foci were morphologically verified by frozen section analysis. The fresh whole mount slices were then laid between two ceramic foam plates and fixed overnight. To test tissue preservation after this procedure, formalin-fixed and paraffin-embedded whole mount sections were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry, fluorescence, and silver in situ hybridization (FISH and SISH, respectively). There were no morphological artifacts on H&E stained whole mount sections from slices that had been fixed between two plates of ceramic foam, and the histological architecture was fully retained. The quality of immunohistochemistry, FISH, and SISH was excellent. Fixing whole mount tissue slices between ceramic foam plates after frozen section examination is an excellent method for processing fresh radical prostatectomy specimens, allowing for a precise identification and collection of fresh tumor tissue without compromising further diagnostic analysis.

Radical cystectomy and ileal orthotopic bladder substitution after radical retropubic prostatectomy: functional and oncological results

Men with good functional results following radical retropubic prostatectomy (RRP) and requiring radical cystectomy (RC) for subsequent bladder carcinoma seldom receive orthotopic bladder substitution. Four patients aged 62-72 years (median 67 years), who had undergone RRP for prostate cancer of stage pT2bN0M0 Gleason score 6 (n = 1), pT2cN0M0 Gleason score 5 and 6 (n = 2) and pT3bN0M0 Gleason score 7 (n = 1) 27 to 104 months before, developed urothelial bladder carcinoma treated with RC and ileal orthotopic bladder substitution. After radical prostatectomy three were continent and one had grade I stress incontinence, and three achieved intercourse with intracavernous alprostadil injections. Follow-up after RC ranged between 27 and 42 months (median 29 months). At the 24-month follow-up visit after RC daily urinary continence was total (0 pad) in one patient, two used one pad for mild leakage, and one was incontinent following endoscopic incision of anastomotic stricture. One patient died of progression of bladder carcinoma, while the other three are alive without evidence of disease. The three surviving patients continued to have sexual intercourse with intracavernous alprostadil injections. Men with previous RRP have a reasonable chance of maintaining a satisfactory functional outcome following RC and ileal orthotopic bladder substitution.

Predicting prostate cancer-specific outcome after radical prostatectomy among men with very high-risk cT3b/4 PCa: a multi-institutional outcome study of 266 patients

BACKGROUND The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option. METHODS In a multi-institutional cohort, 266 patients with very high-risk cT3b/4 PCa treated with RP were identified. All patients underwent RP and pelvic lymph-node dissection. Competing-risk analyses assessed 10-year CSM and OCM before and after stratification for age and Charlson comorbidity index (CCI). RESULTS Overall, 34 (13%) patients died from PCa and 73 (28%) from OCM. Ten-year CSM and OCM rates ranged from 5.6% to 12.9% and from 10% to 38%, respectively. OCM was the leading cause of death in all subgroups. Age and comorbidities were the main determinants of OCM. In healthy men, CSM rate did not differ among age groups (10-year CSM rate for ⩽64, 65-69 and ⩾70 years: 16.2%, 11.5% and 17.1%, respectively). Men with a CCI ⩾1 showed a very low risk of CSM irrespective of age (10-year CSM: 5.6-6.1%), whereas the 10-year OCM rates increased with age up to 38% in men ⩾70 years. CONCLUSION Very high-risk cT3b/4 PCa represents a heterogeneous group. We revealed overall low CSM rates despite the highly unfavorable clinical disease. For healthy men, CSM was independent of age, supporting RP even for older men. Conversely, less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment. Outcome after RP as the primary treatment option in cT3b/4 PCa patients is related to age and comorbidity status.

Very long-term survival patterns of young patients treated with radical prostatectomy for high-risk prostate cancer

OBJECTIVE In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. MATERIALS AND METHODS Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. RESULTS The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). CONCLUSIONS Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.