Prospective evaluation of sexual function in patients receiving cryosurgery as a primary radical treatment for localized prostate cancer

OBJECTIVE

To evaluate prospectively the sexual function of patients undergoing cryosurgery as a primary radical treatment for localized prostate cancer, as the development of 17 G cryotherapy probes has improved the delivery of this treatment, but one of the side‐effects of cryosurgery is the development of erectile dysfunction (ED).

PATIENTS AND METHODS

Between July 2003 and May 2008, 53 patients were treated using an argon‐based third‐generation cryotherapy system (Oncura, Arlington Heights, IL, USA). Prospective data were collected at 6 weeks, 3 months, then 3‐monthly up to 1 year and subsequently 6‐monthly. Patients were followed up for up to 54 months, with a median (mean) follow‐up 36 (30.5) months.

RESULTS

All 53 patients were followed after receiving cryosurgery as primary treatment for prostate cancer; 51 (96.3%) had ED at 6 weeks while two (3.7%) were experiencing partial erections. By 9 months one (2.4%) of 42 patients was fully potent using phosphodiesterase type‐5 inhibitors, and six (14.3%) were experiencing partial erections. By 18 months eight (21%) of 39 patients followed up had regained full potency and by 24 months eight (24%) of 33 patients were fully potent and three (9%) experienced partial erections.

CONCLUSION

While ED is a significant side‐effect of cryotherapy, a considerable proportion of patients who have no ED before treatment (39%) recover full sexual function afterward. Focal nerve‐sparing cryosurgery might be the way forward in an attempt to preserve erectile function in men who had no ED before treatment. Erectile aids should be made available for those patients for whom sexual dysfunction compromises the quality of their life and relationships.     

Micro-focal prostate cancer: a comparison of biopsy and radical prostatectomy specimen features

OBJECTIVES: To study the pathologic features of radical prostatectomy (RP) specimens of patients operated on the basis of a potentially "Insignificant" prostate cancer (Ca P) characterized by one single focus (less than 3mm) of moderately differentiated adenocarcinoma - Gleason score < or =6, out of 6-10 biopsies and to determine which characteristics, if any, are predictive of the presence of a "non significant" prostate cancer in the specimen characterized by a low volume (<0.5 ml) moderately differentiated organ confined, cancer (Gleason score less than 6). PATIENTS AND METHODS: PSA, biopsy features, and surgical specimens of a series of 56 patients submitted to RP for "insignificant Ca P" on TRUS prostate biopsies between 1988 and 2004 were compared regarding the number of tumor foci, Gleason grade and score, tumor volume determined by the cylinder method, as well as extraprostatic extension (EPE) and positive surgical margins (P.SM.). RESULTS: 70% of the patients had multifocal microfocal cancer apart from the index tumor. The presence of grade 4 was ignored by the biopsy in 50% of the cases, however the primary grade was correctly evaluated in more than 70% of the biopsy sets. 42% of the patients had a cancer volume less than 0.5 ml and 29% met the definition of insignificant/unimportant cancer characterized by a moderately differentiated (Gleason score < or =6) of low volume (less than 0.5 ml) however no feature accurately predictive of insignificant cancer could be individualized. In this whole series, only 8% of the patients had EPE. When the pre-operative PSA was <10 ng/ml, 98% of the patients had an organ confined tumor. CONCLUSION: Patients diagnosed with prostate cancer on the basis of one single focus less than 3 mm of moderately differentiated (Gleason < or =6) prostate cancer have 30% of chances of harboring an insignificant tumor in their prostate and are therefore, at risk of being overtreated, however there is at this time no specific feature able to identify these patients pre operatively.     

Androgen and prostate cancer: the role of primary androgen deprivation therapy in localized prostate cancer

BackgroundThe basic mechanisms and clinical efficacy of primary androgen deprivation therapy (PADT), especially combined androgen blockade (CAB) for localized or locally advanced prostate cancer (PCa) have been outlined. An important point relates to which patients are suitable candidates for PADT.MethodsA retrospective review of the efficacy of PADT in 628 patients with localized or locally advanced PCa treated with PADT at seven institutions in Japan was carried out.ResultsIt was found that more than 30% of low- or intermediate-risk localized PCa patients could have their disease controlled over the long-term by PADT alone. Short-term or intermittent PADT could not be recommended because of the possibility of character change in the cancer cells as a result of incomplete androgen ablation.ConclusionAlgorithms are proposed for the treatment of localized PCa not only in low- and intermediate-risk groups, but also in the high-risk group. Future research directions are indicated.     

Salvage Cryosurgery of the Prostate for Failure After Primary Radiotherapy or Cryosurgery: Long-term Clinical,Functional, and Oncologic Outcomes in a Large Cohort at a Tertiary Referral Centre

Background

Salvage cryosurgery (SC) is a recognised option for patients who fail either primary radiation or cryosurgery.

Objective

To report outcomes of patients undergoing SC.

Design, setting, and participants

A consecutive series of 396 patients who had failed either primary radiotherapy or cryosurgery underwent SC between October 1994 and August 2011.

Outcome measurements and statistical analysis

Demographic and clinical parameters before primary and salvage treatment were evaluated; disease-free-survival (DFS), overall-survival (OS), disease-specific-survival (DSS), and complications were assessed.

Results and limitations

Sufficient follow-up data were available for 328 patients. Median age was 65.8 yr (range: 45–81 yr), median serum prostate-specific antigen (PSA) level was 8.0 ng/ml (range: 0.6–290.0 ng/ml). After primary treatment, median time to recurrence was 55 mo (range: 0.0–183.6 mo). SC was performed at a median of 67.5 mo (range: 7.0–212.7 mo) later; median pre-SC PSA level was 4.0 ng/ml (range: 0.1–112.4 ng/ml). Median PSA nadir was 0.2 ng/ml (range: 0.01–70.70 ng/ml), reached after a median of 2.6 mo (range: 2.0–67.3 mo) after SC. Median follow-up was 47.8 mo (range: 1.6–203.5 mo). Respective 5- and 10-yr DFS was 63% and 35%; OS: 74% and 45%; and DSS: 91% and 79%. In univariate analyses, time from primary treatment to SC or recurrence, PSA level before SC, and PSA nadir after SC were all significant predictors of recurrence (p ≤ 0.01). PSA before SC and time to recurrence were also predictive of DSS (p = 0.003 and p = 0.01, respectively). In multivariate analyses, only PSA nadir after SC was predictive of recurrence and DSS (p < 0.001 and p = 0.012, respectively). Complications were rare (range: 0.6–4.6%). Fifty-five patients (16.7%) underwent focal SC. Median PSA nadir after focal SC was 0.44 ng/ml (range: 0.04–20.1 ng/ml). Twenty-seven patients (49%) experienced recurrence. Respective 5- and 10-yr DFS was 47% and 42%; OS: 87% and 81%; and DSS: 100% and 83%.

Conclusions

Our analysis confirms SC as an effective treatment option for patients failing primary therapy. Patients experienced excellent survival outcome and minimal associated morbidity after SC. Focal SC is an efficacious treatment for properly selected patients.     

Radiation for prostate cancer: use of biochemical failure as an endpoint following radiotherapy

The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in endpoints after therapy and in outcome reporting. Over the last 15 years we have collected follow-up information in this new era and struggled with failure definitions using this new tool. Parameters for failure after radiation were especially controversial due to the fact that, unlike surgery, a variable amount of normal prostate function and PSA production remained. In 1996, the ASTRO Consensus Conference established a PSA failure definition based on the available information at the time. It was commonly used for outcome reporting subsequently although criticisms have been voiced and alternate definitions proposed. A recently assembled multi-institutional database was used both for long-term outcome reporting with external beam radiation and to test various other failure definitions. A summary of these results and the associated issues are presented here.     

Quality of life 2 years after salvage cryosurgery for the treatment of local recurrence of prostate cancer after radiotherapy

PURPOSE: Previous research has raised concerns that although salvage cryosurgery may be an effective treatment to prevent the progression of prostate cancer after radiotherapy failure, the quality of life cost many be so severe as to prevent its acceptance as a viable treatment. The present study's purpose was to further the understanding of the quality of life outcomes of salvage cryosurgery. MATERIALS AND METHODS: A total of 46 men with locally recurrent prostate cancer after radiotherapy were recruited to participate in a prospective Phase II clinical trial using salvage cryosurgery. There were 2 questionnaires (i.e., the European Organization of Research and Treatment of Cancer QLQ C30 and the Prostate Cancer Index) administered before cryosurgery, and at 1.5, 3, 6, 12, 18, and 24 months after treatment. RESULTS: Quality of life returned to preoperative levels by 24 months after cryosurgery in all domains, with the exception of urinary and sexual functioning. At 24 months, 29% of men reported urinary bother as a moderate-to-big problem, and 56% reported sexual bother as a moderate-to-big problem. CONCLUSIONS: To our knowledge, this is the first study to evaluate prospectively men's quality of life for 2 years after salvage cryosurgery for locally recurrent prostate cancer after radiotherapy. Long-term impairments in quality of life appear to be limited to the sexual and urinary function domains. Overall quality of life appears to be high. These results support salvage cryosurgery as a viable treatment option.     

Development and internal validation of prediction models for biochemical failure and composite failure after focal salvage high intensity focused ultrasound for local radiorecurrent prostate cancer: Presentation of risk scores for individual patient prognoses

Purpose

Patient selection for focal salvage remains difficult. Therefore, we developed and internally validated prediction models for biochemical failure (BF) and a composite endpoint (CE) following focal salvage high intensity focused ultrasound (HIFU) for radiorecurrent prostate cancer.

Validation of tertiary Gleason pattern 5 in Gleason score 7 prostate cancer as an independent predictor of biochemical recurrence and development of a prognostic model

ObjectiveTo validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5.Material and methodsWe retrospectively reviewed the data from 4,146 patients with localized (pT2–3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model.ResultsOf the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10 ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001).ConclusionsKnowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling.     

前列腺癌组织中TRIB1基因和蛋白异常表达与患者不良预后的相关性

目的研究Tribbles同源蛋白1(TRIB1)在良性前列腺增生和前列腺癌中的表达,并分析其表达水平与患者临床特征及预后的关系。方法在公共基因芯片数据库(GEO)中下载前列腺样本中的相关基因芯片数据,分析TRIB1在前列腺样本中mRNA的表达水平。收集临床手术切除或者穿刺活检的前列腺癌和前列腺增生组织,通过免疫组化检测前列腺癌、前列腺增生组织中TRIB1蛋白的表达。分析TRIB1蛋白和基因的表达水平与患者临床特征及预后的关系。结果前列腺癌患者组织中TRIB1蛋白表达显著上调(P0.01),TRIB1蛋白表达上调与前列腺癌Gleason评分(P0.01)、病理分期(P=0.02)相关,基因芯片数据提示TRIB1基因表达上调与前列腺癌Gleason评分(P=0.02)、病理分期(P=0.01)、无生化复发生存率(BCR-free survival)(P=0.047)相关。结论 TRIB1在前列腺癌组织中表达上调,前列腺组织中检测TRIB1可能有助于判断前列腺癌分化程度并评估预后。     

Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer

We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time “off ” therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score ≥8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.     

Prognostic role of Ki-67 score in localized prostate cancer: A systematic review and meta-analysis

Background

Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically.

Focal cryotherapy for localized prostate cancer: a report from the national Cryo On-Line Database (COLD) Registry

Study Type – Therapy (data synthesis) Level of Evidence 2b What's known on the subject? and What does the study add? The efficacy of prostate cancer screening using PSA testing is still being debated, with conflicting results in randomized trials. The study shows that, even using the hypothesis most favourable to prostate cancer screening with PSA, the net number of years of life does not favour screening.

OBJECTIVE

• ? To evaluate the impact of the implementation a prostate‐specific antigen (PSA) screening programme using the European Randomized Study of Screening for Prostate Cancer (ERSPC) results and taking into account the impact of prostate biopsy and over‐treatment on mortality.

MATERIALS AND METHODS

• ? We used a model based on the number of years of life gained and lost owing to screening, using data reported in the ERSPC.
• ? We conducted a critical evaluation of the ERSPC results and of the Swedish arm of the study.

RESULTS

• ? Accounting for biopsy‐specific mortality and for over‐treatment, the balance of number of years of life was negative in the ERSPC study, with an estimated loss of 3.6 years of life per avoided death.
• ? The number of years of life becomes positive (real gain) only when fewer than 666 screened individuals are required to avoid one death.
• ? We found that in the Swedish arm of the ERSPC there was a biopsy rate of 40% compared with 27% in the ERSPC overall. The over‐treatment rate was also greater with 4.1% compared with 3.4% overall.
• ? For the last 20 years, there has been a marked difference in prostate cancer‐specific mortality between Sweden and the rest of Europe: in 2005, for the age group 65–74 the rate was 140 per 100 000 person years in Sweden and ～80 per 100 000 for the rest of Europe.

CONCLUSION

• ? Overall, PSA testing in Europe is associated with a loss in years of life and should thus not be recommended.

     

Role of dynamic contrast-enhanced magnetic resonance (MR) imaging and proton MR spectroscopic imaging in the detection of local recurrence after radical prostatectomy for prostate cancer

OBJECTIVES: To assess the accuracy of magnetic resonance (MR) spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced MR (DCEMR) in the depiction of local prostate cancer recurrence in patients with biochemical progression after radical prostatectomy (RP). MATERIALS AND METHODS: 1H-MRSI and DCEMR were performed in 70 patients at high risk of local recurrence after RP. The population was divided on the basis of the clinical validation of MR results with the use of a transrectal ultrasound biopsy examination in a group of 50 patients (group A) and the prostate-specific antigen (PSA) serum level restitution after external beam radiotherapy, in a group of 20 patients (group B). RESULTS: In group A, 1H-MRSI analysis alone showed a sensitivity of 84% and a specificity of 88%; the DCEMR analysis alone, a sensitivity of 71% and a specificity of 94%; combined 1HMRSI-DCEMR, a sensitivity of 87% and specificity of 94%. Areas under the receiver operating characteristic (ROC) curve for 1HMRSI, DCEMR, and combined 1HMRSI /DCEMR were 0.942, 0.93,1 and 0.964, respectively. In group B, 1HMRSI alone showed a sensitivity of 71% and a specificity of 83%; DCEMR, a sensitivity of 79% and a specificity of 100%; combined 1HMRSI and DCEMR, a sensitivity of 86% and a specificity of 100%. Areas under the ROC curve for each of these groups were 0.81, 0.923, and 0.94, respectively. CONCLUSION: Our results show that combined 1H-MRSI and DCMRE is an accurate method to identify local prostate cancer recurrence in patients with biochemical progression after RP.     

Expression profile of CD44s,CD44v6, and CD44v10 in localized prostate cancer: Effect on prognostic outcomes following radical prostatectomy

ObjectivesTo investigate the expression of CD44 standard form (CD44s) and 2 major variant exons (CD44v6 and CD44v10) in localized prostate cancer (PC) to determine the prognostic significance of these markers following radical prostatectomy (RP).Materials and methodsExpression levels of CD44s, CD44v6, and CD44v10 in RP specimens from 160 consecutive patients with clinically localized PC were evaluated by immunohistochemical staining.ResultsOf these 3 markers, expression level of CD44v6 was closely associated with several conventional prognostic factors. Univariate analysis identified CD44v6 expression in addition to serum prostate-specific antigen level, Gleason score, seminal vesicle invasion, and surgical margin status as significant predictors for biochemical recurrence (BR). Of these significant factors, CD44v6 expression, serum prostate-specific antigen level, and surgical margin status appeared to be independently associated with BR on multivariate analysis. We observed significant differences in BR-free survival according to the positive numbers of these 3 independent factors; i.e., BR occurred in 0 (0%) of 42 patients who had negative results for risk factors, 9 (16.7%) of 54 who had positive results for 1 risk factor, and 31 (48.4%) of 64 who had positive results for 2 or 3 risk factors.ConclusionsAssessment of the expression levels of CD44v6 in RP specimens in addition to conventional prognostic parameters would contribute to the accurate prediction of the biochemical outcome in patients with localized PC who underwent RP.     

Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10)

PURPOSE: A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer. PATIENTS AND METHODS: Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded. RESULTS: Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive. CONCLUSION: The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.