Age-adjusted validation of the most stringent criteria for active surveillance in low-risk prostate cancer patients

BACKGROUND:

The authors tested the performance of the currently used clinical criteria reported in populations studied by van den Bergh et al and Carter et al for the selection of patients with prostate cancer (PCa) for active surveillance (AS) according to age.

METHODS:

Data were analyzed from 893 patients who underwent with radical prostatectomy (RP). The authors investigated the rates of unfavorable PCa at RP (extracapsular extension, seminal vesicle or lymph node invasion, or Gleason score 7‐10) in patients who fulfilled AS criteria according to age tertiles (ages ≤63 years, 63.1 to 69 years, and >69 years). Area under the plasma concentration time curve (AUC) analyses tested the criteria for predicting unfavorable PCa. Then, the patients were stratified according to the cutoff age of 70 years. Multivariate analyses were used to test the role of age in predicting unfavorable PCa.

RESULTS:

The rate of unfavorable PCa characteristics was between 24% and 27.8%. In the van den Bergh et al population, after age 70 years, the rate of unfavorable PCa characteristics was 41% compared with 23.2% and 24.1% in patients in the previous age tertiles (ages ≤63 years and 63.1 to 69 years, respectively). In the Carter et al population, the rate of unfavorable PCa was 41.2% compared with 17.3% and 18.6% in the previous age tertiles (ages ≤63 years and 63.1 to 69 years, respectively). When the 70‐year age cutoff was used, unfavorable PCa was identified in 17.9% to 23.6% of patients aged <70 years versus 4% to 41.2% of patients aged >70 years (all P < .001). AUC analyses revealed significantly lower performance in older patients. In multivariate analyses, after adjustment for prostate‐specific antigen, prostate volume, and the number of cores, age represented an independent predictor of unfavorable PCa.

CONCLUSIONS:

The currently used AS criteria performed significantly better for patients aged <70 years. The authors concluded that the current results should be taken into account when deciding whether to offer active surveillance to patients with low‐risk PCa. Cancer 2012;. © 2011 American Cancer Society.     

Anxiety and distress during active surveillance for early prostate cancer

BACKGROUND:

Patients on active surveillance (AS) for early prostate cancer (PC) may experience feelings of anxiety and distress while living with “untreated” cancer. In this study, these feelings were quantified, and their associations with various psychologic, medical, demographic, and decision‐related factors were assessed.

METHODS:

Men with recently diagnosed PC who participated in a prospective protocol‐based AS program (the Prostate Cancer Research International: Active Surveillance study [PRAIS]) received a questionnaire (N = 150). Scores concerning decisional conflict (the Decisional Conflict Scale), depression (the Center for Epidemiologic Studies Depression Scale), generic anxiety (the abridged State‐Trait Anxiety Inventory), and PC‐specific anxiety (the Memorial Anxiety Scale for Prostate Cancer) were compared with reference values and the literature. Associations with scores on physical health (the Medical Outcomes Study 12‐item short‐form Physical Component Summary), personality (the Eysenck Personality Questionnaire), shared decision‐making, knowledge of PC, and demographic and medical parameters were determined with univariate and multivariate linear regression analyses.

RESULTS:

The questionnaire response rate was 86% (129 of 150 men). Of all respondents, 81%, 92%, 83%, and 93% scored better than reference values for clinically significant uncertainty regarding the treatment decision, depression, generic anxiety, and PC‐specific anxiety, respectively. Scores were comparable to or more favorable than those of men (reported in literature) who underwent other treatments for localized PC. In multivariate analysis, the following associations emerged: a perceived important role of the physician in shared decision‐making was associated with higher decisional conflict, better physical health was associated with lower depression, neurotic personality was associated with higher depression and with generic and PC‐specific anxiety, and higher prostate‐specific antigen level was associated with higher PC‐specific anxiety.

CONCLUSIONS:

Men on protocol‐based AS mainly reported favorable levels of anxiety and distress. A neurotic personality score was associated with unfavorable effects. These findings may help to optimize patient selection for AS or to select men for supportive measures. Cancer 2009. © 2009 American Cancer Society.     

Retropubic versus perineal radical prostatectomy in early prostate cancer: eight-year experience

BACKGROUND: Prostate cancer is the most common malignancy in men and the second leading cause of cancer death. A randomized study was performed on patients with localized prostate cancer and treated with radical prostatectomy using the perineal or the retropubic approach comparing oncological outcomes, cancer control, and functional results. STUDY DESIGN: Between 1997 and 2004, in a randomized study 200 patients underwent a radical prostatectomy performed by retropubic (100 patients) or perineal (100 patients) approach. RESULTS: Differences between hospital stay, duration of catheter drainage, intraoperative blood loss, and transfusion requirements were statistically significant in favor of perineal prostatectomy. Differences between positive surgical margins and urinary continence in the two groups were not statistically significant at 6 and 24 months. Differences between erectile function at 24 months were statistically significant in favor of retropubic prostatectomy. CONCLUSIONS: Radical perineal prostatectomy is an excellent alternative approach for radical surgery in the treatment of early prostate cancer.     

Primary radiotherapy versus radical prostatectomy for high-risk prostate cancer: a decision analysis

BACKGROUND:

Two evidence‐based therapies exist for the treatment of high‐risk prostate cancer (PCA): external‐beam radiotherapy (RT) with hormone therapy (H) (RT + H) and radical prostatectomy (S) with adjuvant radiotherapy (S + RT). Each of these strategies is associated with different rates of local control, distant metastasis (DM), and toxicity. By using decision analysis, the authors of this report compared the quality‐adjusted life expectancy (QALE) between men with high‐risk PCA who received RT + H versus S + RT versus a hypothetical trimodality therapy (S + RT + H).

METHODS:

The authors developed a Markov model to describe lifetime health states after treatment for high‐risk PCA. Probabilities and utilities were extrapolated from the literature. Toxicities after radiotherapy were based on intensity‐modulated radiotherapy series, and patients were exposed to risks of diabetes, cardiovascular disease, and fracture for 5 years after completing H. Deterministic and probabilistic sensitivity analyses were performed to model uncertainty in outcome rates, toxicities, and utilities.

RESULTS:

RT + H resulted in a higher QALE compared with S + RT over a wide range of assumptions, nearly always resulting in an increase of >1 quality‐adjusted life year with outcomes highly sensitive to the risk of increased all‐cause mortality from H. S + RT + H typically was superior to RT + H, albeit by small margins (<0.5 quality‐adjusted life year), with results sensitive to assumptions about toxicity and radiotherapy efficacy.

CONCLUSIONS:

For men with high‐risk PCA, RT + H was superior to S + RT, and the result was sensitive to the risk of all‐cause mortality from H. Moreover, trimodality therapy may offer local and distant control benefits that lead to optimal outcomes in a meaningful population of men. Cancer 2012;. © 2011 American Cancer Society.     

PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: results from the European randomized study of screening for prostate cancer, Sweden section

This study reports the outcome of active surveillance in men with PSA screening-detected prostate cancer (PC), and PSA doubling time (PSADT) was evaluated as a predictor of selecting patients to active treatment or surveillance. On December 31, 1994, 10,000 men were randomized to biennial PSA testing. Through to December 2004, a total of 660 men were diagnosed with PC, of whom 270 managed with initial surveillance. Of these 270 patients, 104 (39%) received active treatment during follow-up, 70 radical prostatectomy, 24 radiation and 10 endocrine treatment. Those who received active treatment during follow-up (mean 63 months) were significantly younger (62.6 vs. 65.5 years, p < 0.0001) and had a shorter PSADT (3.7 vs. 12 years, p < 0.0001). PSA relapse was observed in 9 of 70 patients who received RRP during a mean follow-up of 37 months. Seven of these nine PSA relapses were in the patients with preoperative PSADT < 2 years. None of the 37 operated patients with a PSADT > 4 years had a PSA relapse. In a Cox regression analysis adjusted for PSA, ratio-free PSA and amount of cancer in biopsy, only the preoperative PSADT was statistically significant predictor of PSA relapse in p = 0.031. The optimal candidate for surveillance is a man with early, low-grade, low-stage PC and a PSADT > 4 years. In younger men with a PSADT of less than 4 years, surveillance does not seem to be a justified alternative, and patient should be informed about the risk with such an approach.     

Patterns of care and treatment trends for Canadian men with localized low-risk prostate cancer: an analysis of provincial cancer registry data

BackgroundMany prostate cancers (pcas) are indolent and, if left untreated, are unlikely to cause death or morbidity in a man’s lifetime. As a result of testing for prostate-specific antigen, more such cases are being identified, leading to concerns about “overdiagnosis” and consequent overtreatment of pca. To mitigate the risks associated with overtreatment (that is, invasive therapies that might cause harm to the patient without tangible benefit), approaches such as active surveillance are now preferred for many men with low-risk localized pca (specifically, T1/2a, prostate-specific antigen ≤ 10 ng/mL, and Gleason score ≤ 6). Here, we report on patterns of care and treatment trends for men with localized low-risk pca.ResultsThe provinces varied substantially with respect to the types of primary treatment received by men with localized low-risk pca. From 2010 to 2013, many men had no record of surgical or radiation treatment within 1 year of diagnosis—a proxy for active surveillance; the proportion ranged from 53.3% in Nova Scotia to 80.8% in New Brunswick. Among men who did receive primary treatment, the use of radical prostatectomy ranged from 12.0% in New Brunswick to 35.9% in Nova Scotia. The use of radiation therapy (external-beam radiation therapy or brachytherapy) ranged from 4.1% in Newfoundland and Labrador to 17.6% in Alberta. Treatment trends over time suggest an increase in the use of active surveillance. The proportion of men with low-risk pca and no record of surgical or radiation treatment rose to 69.9% in 2013 from 46.1% in 2010 for all provinces combined.ConclusionsThe provinces varied substantially with respect to patterns of care for localized low-risk pca. Treatment trends over time suggest an increasing use of active surveillance. Those findings can further the discussion about the complex care associated with pca and identify opportunities for improvement in clinical practice.     

Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival

Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10-40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61. 2 years underwent radical retropubic prostatectomy. Levels < or = 0.01 ng ml-1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml-1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6-70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir < or = 0.01 ng ml-1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy.     

Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer

Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression.     

机器人辅助前列腺癌根治术治疗大体积前列腺癌的临床应用研究

目的:评估大体积前列腺癌行机器人辅助前列腺癌根治术（RALP）的疗效和安全性,探讨前列腺体积对手术难度的影响。方法:回顾性分析2013年1月至 2017年3月应用机器人辅助前列腺癌根治术治疗大体积前列腺癌35例患者临床资料（前列腺体积≥100 ml）,tPSA水平为6.5~58.5 ng/ml,平均（19.5±8.7） ng/ml,Gleason评分≤6分4例,7分19例（3+4分8例,4+3分11例）,8分7例,9~10分5例。3例有经尿道前列腺电切手术史,5例术前行新辅助内分泌治疗。手术方式均采用经腹膜内入路机器人辅助腹腔镜前列腺癌根治术,高危患者同时行扩大盆腔淋巴结清扫并术后辅助内分泌治疗12~18个月。结果:35例患者均顺利完成手术,无中转开放、直肠损伤及输血病例。手术时间为86~191 min,平均（154±19.8） min;术中出血量45~330 ml,平均（132±60.5） ml;住院时间5~9 d,平均（6.5±0.8） d。术后病理切缘阳性3例（8.6%）;盆腔淋巴结阳性2例（5.7%）。术后漏尿1例,术后2周停止。1例吻合口狭窄,经尿道扩张后排尿通畅。术后1~12个月复查,无生化复发病例,术后3个月有不同程度尿失禁9例（25.7%）,1年内控尿满意33例（94.3%）。结论:大体积前列腺癌手术难度明显增大,需在具备丰富手术经验的前提下完成,采取合理的技术优化可以明显降低手术难度。     

Applying precision medicine to the active surveillance of prostate cancer

The recent introduction of a variety of molecular tests will potentially reshape the care of patients with prostate cancer. These tests may make more accurate management decisions possible for those patients who have been “overdiagnosed” with biologically indolent disease, which represents an exceptionally small mortality risk. There is a wide range of possible applications of these tests to different clinical scenarios in patient populations managed with active surveillance. Cancer 2015;121:3435–43. © 2015 American Cancer Society.     

Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

Role of repeated biopsy of the prostate in predicting disease progression in patients with prostate cancer on active surveillance

BACKGROUND: Active surveillance (AS) with deferred treatment is an established management option for patients with prostate cancer and favorable clinical parameters. The impact of repeat biopsy after diagnosis was examined in a cohort of men with prostate cancer on AS. METHODS: In all, 186 men with prostate cancer with favorable parameters or who refused treatment were conservatively managed by AS. Of these, 92 patients had at least 1 biopsy after diagnosis. Patients were followed every 3 to 6 months with prostate-specific antigen (PSA) and physical examination and were offered rebiopsy annually or if there were any changes on physical examination or in the PSA value. Disease progression while on AS was defined as having > or =1 of the following: > or =cT2b disease, > or =3 positive cores, >50% of cancer in at least 1 core, or a predominant Gleason pattern of 4 in rebiopsies. RESULTS: The median age of the patients at the time of diagnosis was 67 years (range, 49-78 years). The median follow-up was 76 months (range, 20-169 months). Of the 92 patients who underwent repeat biopsies, 42 patients, 25 patients, 13 patients, 10 patients, and 2 patients had 1, 2, 3, 4, and 5 rebiopsies, respectively. A total of 34 patients (36%) demonstrated disease progression on rebiopsy. The first rebiopsy was positive for cancer in 48 patients (52.2%) and negative in 44 patients (47.8%). The 5-year actuarial progression-free probability was 82% for patients with a negative first repeat biopsy compared with 50% for patients with a positive first rebiopsy (P = .02). A PSA doubling time <67 months was associated an increased risk of disease progression on biopsy. CONCLUSIONS: Negative rebiopsy in patients with prostate cancer on AS is associated with low-volume disease. The result of first repeated biopsy appears to have a strong impact on disease progression. Patients with a positive first repeated biopsy should be considered for treatment. An intensive biopsy protocol within the first 2 years is required to identify and treat those patients.