Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech.

Laparoscopic Radical Prostatectomy with a Remote Controlled Robot.

PURPOSE: Robotics in surgery is a recent innovation. This technology offers a number of attractive features in laparoscopy. It overcomes the difficulties with fixed port sites by restoring all 6 degrees of freedom at the instrument tips, provides new possibilities for miniaturization of surgical tasks and allows remote controlled surgery. We investigated the applicability of remote controlled robotic surgery to laparoscopic radical prostatectomy. MATERIALS AND METHODS: Our previous experience with laparoscopic prostatectomy served as a basis for adapting robotic surgery to this procedure. A surgeon at a different location who activated the tele-manipulators of the da Vinci∗ robotic system performed all steps of the intervention. A scrub nurse and second surgeon who stood at patient side had limited roles to port and instrument placement, exposure of the operative field, assistance in hemostasis and removal of the operative specimen. Our patient was a 63-year-old man presenting with a T1c tumor discovered on 1 positive sextant biopsy with a 3+3 Gleason score and 7 ng./ml. preoperative serum prostate specific antigen. RESULTS: The robot provided an ergonomic surgical environment and remarkable dexterity enhancement. Operating time was 420 minutes, and the hospital stay lasted 4 days. The bladder catheter was removed 3 days postoperatively, and 1 week later the patient was fully continent. Pathological examination showed a pT3a tumor with negative margins. CONCLUSIONS: Robotically assisted laparoscopic radical prostatectomy is feasible. This new technology enhances surgical dexterity. Further developments in this field may have new applications in laparoscopic tele-surgery.

Introducing a prognostic score for pretherapeutic assessment of seminal vesicle invasion in patients with clinically localized prostate cancer.

PURPOSE: To identify prostate cancer patients who will have the most likely benefit from sparing the seminal vesicles during 3D conformal radiation therapy. METHODS AND MATERIALS: From 1988 to 2001, 532 patients underwent radical prostatectomy for clinically localized prostate cancer. Primary endpoint was the pathological evidence of seminal vesicle invasion. Variables for univariate and multivariate analyses were age, prostate weight, clinical stage, PSA level, Gleason score, number and site of positive prostate sextant biopsies. Multivariate logistic regression with backward stepwise variable selection was used to identify a set of independent predictors of seminal vesicle invasion, and the variable selection procedure was validated by non-parametric bootstrap. RESULTS: Seminal vesicle invasion was reported in 14% of the cases. In univariate analysis, all variables except age and prostate weight were predictors of seminal vesicle invasion. In multivariate analysis, only the number of positive biopsies (P<0.0001), Gleason score (P<0.007) and PSA (P<0.0001) were predictors for seminal vesicles invasion. Based on the multivariate model, we were able to develop a prognostic score for seminal vesicle invasion, which allowed us to discriminate two patient groups: A group with low risk of seminal vesicles invasion (5.7%), and the second with a higher risk of seminal vesicles invasion (32.7%). CONCLUSIONS: Using the number of positive biopsies, Gleason score and PSA, it is possible to identify patients with low risk of seminal vesicles invasion. In this population, seminal vesicles might be excluded as a target volume in radiation therapy of prostate cancer.

Laparoscopic retroperitoneal nephrectomy for Aspergillus-infected polycystic kidney.

BACKGROUND AND PURPOSE: The management of polycystic kidney disease is mostly restricted to conservative measures. However, nephrectomy may be indicated in particular cases, especially when there are infective complications. To decrease the morbidity of the procedure, the laparoscopic approach has become appealing. We present a laparoscopic retroperitoneal approach to complicated polycystic kidney disease in a high-risk patient. CASERESPORT: We performed right retroperitoneal laparoscopic nephrectomy in a 39-year-old man who had autosomal polycystic kidney disease and had undergone heart transplantation. The immunosuppressed patient presented with severe flank pain, generalized signs of infection, and acute renal insufficiency. With the patient in the right lateral decubitus position, the retroperitoneal space was entered by the open technique, and the posterior pararenal space was developed with finger dissection. Five trocars were used. After the renal vessels had been secured and divided, the cysts were successively punctured, gradually shrinking the operative specimen. The kidney was placed in an Endo-catch and removed after morcellation, with no need to enlarge the 2-cm lumbotomy. The operating time was 80 minutes, and the hospital stay was 4 days. Histologic examination revealed a polycystic kidney with Aspergillus infection. CONCLUSION: The laparoscopic approach is a less-invasive option for removing a polycystic kidney when nephrectomy is indicated. The retroperitoneal route has the advantage of minimizing infection risks because of the absence of peritoneal opening.

Do prognostic parameters of remission versus relapse after Bacillus Calmette-Guérin (BCG) immunotherapy exist?. analysis of a quarter century of literature.

OBJECTIVE: To review prognostic factors identified in clinical trials for remission versus relapse after intravesical adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy for superficial bladder cancer (Ta, T1, and carcinoma in situ). MATERIALS AND METHODS: Information was retrieved by a MEDLINE search of the English literature. Indexing terms comprised bladder cancer, bladder neoplasm, BCG vaccine, superficial bladder cancer, immunotherapy, intravesical therapy, prognostic marker, and Bacillus Calmette-Guérin. Fifty clinical studies were assessed for the strength of their results on the therapeutic response to BCG instillation. Emphasis was placed on clinical trials that assessed tumor and/or host characteristics, immunological reactions, recurrence rates, progression rates and disease-specific survival after BCG. RESULTS: The predictive value of host factors is extremely controversial, but marked adverse reactions to BCG instillation appear to be associated with a better tumor response. Traditional pathological tumor characteristics, molecular markers (p53) and immunological status (PPD skin test) do not appear to have prognostic value in this setting. There is increasing evidence that immunologic markers are predictive of the BCG response, but most of them have not yet been assessed in large prospective studies. Histologic/cytologic response criteria are the critical determinant of post-BCG outcome. CONCLUSIONS: After a quarter century of clinical research, no independent prognostic factor for the bladder tumor response to BCG has yet been identified. Sophisticated individual therapeutic approaches (SITA) appear to be the most promising. Nomograms based on host, tumor and immunological characteristics may help with clinical decision-making and with rationalized BCG schedule design.

Patient reported sexual function following laparoscopic radical prostatectomy.

PURPOSE: We evaluated the sexual function of patients who underwent laparoscopic radical prostatectomy. We assessed the effect of unilateral or bilateral preservation of the neurovascular bundle on the ability to achieve erections and have sexual intercourse postoperatively. MATERIAL AND METHODS: Between May 1998 and September 2001, 232 men underwent laparoscopic radical prostatectomy for localized prostate cancer at our institution. Sexual function questionnaires were given to the patients preoperatively. The study included 143 patients who were potent preoperatively. After the procedure the surgeon noted whether he performed unilateral, bilateral or no nerve sparing. Sexual function questionnaires were collected at 1, 3, 6 and 12 months after surgery. RESULTS: Of the 143 patients, 100, 80, 48 and 26 responded to the questionnaire at 1, 3, 6 and 12 months respectively. Of the nonnerve sparing group 11.7%, 11.1%, 16.6% and 30%, of the unilateral nerve sparing group 20%, 35%, 41.6% and 50% and of the bilateral nerve sparing group 32.5%, 41.1%, 29.1% and 87.5% respectively reported spontaneous erections 1, 3, 6 and 12 months after surgery, respectively. The overall incidence of positive lateral surgical margins in pT2 cases treated with a nerve sparing procedure was 8.4%. CONCLUSIONS: The overall rate of patients who had erections preoperatively and maintained erections after surgery (53.8%) is comparable to the results for open surgery. Patients with bilateral preservation did better than those with unilateral preservation. Our preliminary results show a promising rate of potency at 1 year after laparoscopic radical prostatectomy.

Location of positive surgical margins after retropubic, perineal, and laparoscopic radical prostatectomy for organ-confined prostate cancer.

OBJECTIVES: To evaluate and compare the location of positive surgical margins after retropubic, perineal, and laparoscopic radical prostatectomy for organ-confined prostate cancer (pT2). METHODS: From 1988 to 2001, 538 patients underwent radical prostatectomy for clinically localized prostate cancer. Patient age at surgery, clinical stage, preoperative prostate-specific antigen, and Gleason score of positive biopsies were noted. Postoperatively, specimen weight, final Gleason score, and capsular, seminal vesicle, and lymph node status, as well as tumor volume, were studied. The incidence and location of positive margins and the pathologic stage were noted according to the surgical approach. RESULTS: A total of 371 patients (69.5%) had organ-confined tumors. Of the 371 patients, 116 underwent the retropubic, 86 the perineal, and 169 the laparoscopic approach, and positive surgical margins were noted in 22 (18.9%), 12 (13.9%), and 32 (18.9%) patients, respectively. Positive surgical margins were reported in 72 specimen locations, 32 (44.4%) at the apex, 17 (23.6%) at the bladder neck, and 29 (31.9%) posterolaterally. The distribution for the retropubic, perineal, and laparoscopic approaches was apex in 50%, 33.3%, and 44.4%, bladder neck in 29.1%, 41.7%, and 13.9%, and posterolaterally in 20.8%, 25%, and 41.6%, respectively. CONCLUSIONS: In our series, each approach had a specific high-risk location of positive margins: the apex for the retropubic, the bladder neck for the perineal, and posterolaterally for the laparoscopic approach. Improvements in the surgical techniques should take these specific locations under consideration to decrease the incidence of positive surgical margins.

Prognostic consequences of the location of positive surgical margins in organ-confined prostate cancer.

INTRODUCTION: The purpose of the present study was to evaluate and compare the risk of progression in organ-confined prostate cancers (stage pT2), according to the location of positive surgical margins. MATERIALS AND METHODS: Between 1988 and 2001, 538 consecutive men underwent radical prostatectomy for localized prostate cancer. All patients had preoperative physical examinations, serum PSA assays (Hybritech assay, N.l. <4 ng/ml) and ultrasound-guided sextant biopsies to confirm diagnosis. Radical prostatectomy specimens were analyzed according to the Stanford protocol. Positive margins were classified as single or multiple and main locations (apex, bladder neck and posterolateral) were noted. Postoperative follow-up data were obtained through routine serum PSA assays. Biochemical recurrence was defined as a single postoperative PSA level >0.2 ng/ml. Biochemical progression was studied in patients with organ-confined tumors (stage pT2) according to the location of the single positive margin. Kaplan-Meier analysis was performed to determine the actuarial biochemical recurrence-free likelihood and the log-rank test was used for statistical analysis. Differences were considered significant when the p value was <0.05. RESULTS: 371 patients had organ-confined tumors, and 60 patients (16.1%) had solitary positive margins (apex 26, bladder neck 14, posterolaterally 20). Eleven patients (18.3%) had biochemical progression. 5-year biochemical free progression was 54.5, 76.9 and 87.9% for apex, bladder and the posterolateral location, respectively (p < 0.05). CONCLUSIONS: In the present study, a positive surgical margin at the apex was associated with worse clinical prognosis compared to the bladder neck and posterolateral locations.

Radical prostatectomy by the retropubic, perineal and laparoscopic approach: 12 years of experience in one center.

OBJECTIVES: We retrospectively evaluated the oncological outcome of radical prostatectomy performed by the retropubic, perineal and laparoscopic approaches. METHODS: From 1988 to 2000, 401 patients underwent radical prostatectomy for localized prostate cancer by the retropubic, perineal or laparoscopic approach. Age, clinical stage, preoperative PSA and Gleason score of positive biopsies were noted. Operating time, complication rate, transfusion rate, length of hospital stay, catheterization time and pathological results were reviewed. Kaplan-Meier analysis was used to evaluate the likelihood of biochemical recurrence (PSA > or =0.2 ng/ml). RESULTS: There were no significant differences between the three groups regarding preoperative characteristics, except for PSA (21.4 ng/ml, 13.2 ng/ml, and 11.6 ng/ml for the retropubic, perineal, and laparoscopic approach, p<0.05) and the frequency of stage T1c tumors (31.7%, 47.1% and 63.5%, respectively, p<0.05). The operating time was significantly longer in the laparoscopic approach (285 min) compared to the retropubic and perineal techniques (197 min and 178 min, respectively). The retropubic approach was associated with a higher transfusion rate (26.2% versus 15.9% and 2.9% with the perineal and laparoscopic approaches), longer bladder catheterization time (15.9 days versus 11.7 days and 6.8 days, respectively), and longer hospital stay (15.2 days versus 8.5 days and 7.4 days, respectively) (p<0.05 for each). With the retropubic, perineal and laparoscopic approaches, medical complication rates were 8.3%, 4.2% and 5.1%, and surgical complication rates were 16.5%, 12.7% and 13.1%, respectively. The rates of pathological stage pT2 tumors were 62.1%, 72.2% and 75.9%, in the retropubic, perineal and laparoscopic groups, respectively. Positive surgical margins in pT2 tumors were noted in 19%, 14% and 22%, respectively. The actuarial 3-year recurrence-free survival rates were not significantly different between the three techniques (75%, 85.2% and 84.1%, respectively; 91.7%, 95.8% and 90.4% among patients with organ-confined tumors). CONCLUSION: Despite changes in patient selection criteria over time, and the relatively short follow-up, this study showed no significant difference in oncologic outcome between the retropubic, perineal and laparoscopic approaches to radical prostatectomy.

Prognostic significance of tumor volume after radical prostatectomy: a multivariate analysis of pathological prognostic factors.

OBJECTIVES: To analyze the association between Gleason score, stage and status of surgical margins with tumor volume in prostate cancer progression after radical prostatectomy. METHODS: 200 consecutive radical prostatectomy specimens were analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well as pathological results were noted. A biochemical recurrence was defined as a single, postoperative detectable PSA level (>0.2 ng/ml). Tumor volume was compared to postoperative staging, Gleason score, and surgical margin status to predict tumor progression. Univariate and multivariate analysis using stepwise logistic regression were used to identify parameters with additional prognostic value. RESULTS: Pathological results of the prostatectomy specimens showed 149 (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57 cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively (p<0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc, respectively (p<0.0001). Five-year progression-free actuarial survival was 69.7%. Using univariate analysis, tumor progression correlated with final Gleason score (p<0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage (p<0.0001). In a multivariate analysis, tumor progression correlated only with the final Gleason score (p=0.04) and stage (p=0.0002). CONCLUSION: Gleason score and pathological stage are independent factors to predict prostate cancer progression after radical prostatectomy. When these parameters are known, tumor volume does not provide additional information.