Active Surveillance For Low-risk Prostate Cancer Research Articles

Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer

BackgroundAssociations have been documented recently between some of the 23 single nucleotide polymorphisms newly discovered with the Collaborative Oncological Gene-environment Study iCOGS array that indicate prostate cancer (PCa) risk and aspects of disease aggressiveness. The utility of these iCOGS SNPs remains to be determined in active surveillance (AS). ObjectiveTo determine associations between iCOGS SNPs and upgrading among men who underwent surgical treatment and AS for low-risk PCa. Design, setting, and participantsThe genotypes of the 23 iCOGS SNPs were determined for all white subjects with biopsy Gleason score (GS) 6 including 950 men who underwent definitive treatment with surgery and 209 men who elected AS. The clinical and pathologic characteristics were documented for all subjects. Outcome measures and statistical analysisMen who underwent surgery were grouped according to their pathologic GS (upgraded was defined as GS ≥7; nonupgraded remained GS 6). Men who were enrolled in AS were also grouped according to their GS on subsequent surveillance biopsies. Statistical analyses were performed comparing the genotypes between the upgraded and nonupgraded groups. Results and limitationsOverall, 31% and 34% of men were upgraded in the surgery and AS cohorts, respectively. Three iCOGS SNPs were significantly associated with the risk of upgrading in the surgical cohort. After correction for multiple testing, only rs11568818 on chromosome 11q22 remained significantly associated with upgrading. Assessment of this allele in the AS cohort reveals that it was present at noteworthy higher frequencies in men with high-grade disease on surveillance biopsies compared with nonupgraded men (p=0.003). This study was primarily limited by the homogeneous patient population. ConclusionsThis is the first report of a SNP on chromosome 11q22 associated with higher grade disease in a surgical cohort that is also validated for eventual upgrading in a prospective AS cohort. Patient summaryWe examined the relationship between a group of genetic markers and prostate cancer (PCa) aggressiveness in a group of patients who underwent surgery for PCa and a group of patients who were enrolled in active surveillance. We found that these genetic markers helped predict which patients had more aggressive disease in both groups.

Prospective quality‐of‐life outcomes for low‐risk prostate cancer: Active surveillance versus radical prostatectomy

For patients with low-risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa. Beginning in 2007, HRQoL data from validated questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND Medical Outcomes Study short-form survey) were collected by the Center for Prostate Disease Research in a multicenter national database. Patients aged ≤75 years who were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for 3 years. Mean scores were estimated using generalized estimating equations adjusting for baseline HRQoL, demographic characteristics, and clinical patient characteristics. Of the patients with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis revealed that patients in the RP group had significantly worse sexual function, sexual bother, and urinary function at all time points compared with patients in the AS group. Differences in mental health between groups were below the threshold for clinical significance at 1 year. In this study, no differences in mental health outcomes were observed, but urinary and sexual HRQoL were worse for patients who underwent RP compared with those who underwent AS for up to 3 years. These data offer support for the management of low-risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant declines in mental health.

Association of baseline perineural invasion with shorter time to progression in men with prostate cancer undergoing active surveillance: Results from the REDEEM study.

23 Background: Perineural invasion (PNI) on prostate cancer (PC) biopsies has been associated with disease upgrading among those undergoing radical prostatectomy. However, the clinical significance of PNI in men on active surveillance (AS) has been evaluated by a limited number of studies. Thus, we sought to evaluate the association of PNI with time to clinical and pathological progression in men with PC on AS. Methods: Retrospective analysis of 289 men 48 to 82 years old on AS for low-risk PC (T1c-T2a), Gleason ≤6, ≤3 positive cores, ≤50% of any core involved, prostate-specific antigen (PSA) ≤11ng/ml, life expectancy >5 years and follow-up data in the REduction by Dutasteride of clinical progression Events in Expectant Management study. Progression was divided in pathological (>3 positive cores, >50% core involvement or Gleason >6 in a repeat biopsy) or therapeutic (any treatment for PC) or both. Time to progression was analyzed with Kaplan-Meier plots, log-rank tests and Cox model adjusting for age, PSA density, percent cores involved, maximum core involvement and treatment. Results: A total of 11 (4%) patients had PNI on baseline biopsy. PNI was associated with higher tumor length and maximum core involvement (all P<0.05). PNI was not associated with patient’s age, race, PSA levels or density, percent or number of positive cores. After a median follow-up of 37 months, 125 (43%) patients developed progression. Of these, 95 (76%) patients had pathological and 30 (24%) had therapeutic progression. In univariable analysis, patients with baseline PNI had a shorter time to overall and pathological progression (HR=2.62, 95%CI=1.31-5.23, P=0.006 and HR=2.42, 95%CI=1.03-5.66, P=0.041, respectively). Similar results were obtained in multivariable analysis for overall and pathological progression (HR=2.26, 95%CI=1.10-4.68, P=0.028 and HR=2.13, 95%CI=0.88-5.13, P=0.092, respectively). Conclusions: Among patients with PC on AS, PNI is independently associated with shorter time to progression. Thus, PNI may be used to help select patients for AS and stratify them according to the risk of disease progression.

Obesity Is Associated with Risk of Progression for Low-risk Prostate Cancers Managed Expectantly

BackgroundActive surveillance (AS) is an expectant management strategy for prostate cancer (PCa). The impact of obesity on progression is not well characterized in this population. ObjectiveTo determine if obesity is associated with progression in men on AS for low-risk PCa. Design, setting, and participantsMen undergoing AS for low-risk PCa (no Gleason pattern ≥4, three or fewer cores involved or one-third or less of the total number of cores involved, and no core with >50% cancer involvement) were identified at our institution. Outcome measurements and statistical analysisThe outcomes were pathologic progression (defined as no longer meeting low-risk criteria on follow-up biopsy) and therapeutic progression (defined as intent to initiate active treatment). Kaplan-Meier curves and multivariable logistic regression and Cox proportional hazards models were used, with separate models for reclassification at confirmatory biopsy (first biopsy after diagnostic biopsy) and progression beyond confirmatory biopsy. Results and limitationsIn this cohort of 565 men (median follow-up: 48 mo), 124 (22%) were obese (body mass index [BMI] ≥30kg/m2). Pathologic and therapeutic progression occurred in 168 men (30%) and 172 men (30%), respectively. No association was noted between obesity and risk of progression at the confirmatory biopsy. However, beyond confirmatory biopsy, obesity was associated with a greater probability of pathologic progression (p=0.007) and therapeutic progression (p=0.007) in Kaplan-Meier analyses. In adjusted Cox models, each 5-unit increase in BMI was associated with an increased risk of pathologic progression (hazard ratio [HR]: 1.5; 95% confidence interval [CI], 1.1–2.1; p=0.02) and therapeutic progression (HR: 1.4; 95% CI, 1.0–1.9; p=0.05). The main limitation is the retrospective design, limiting the ability to assess BMI changes over time. ConclusionsObesity was associated with a significantly increased risk of progression beyond the confirmatory biopsy. This suggests an increased risk of long-term biologic progression rather than solely misclassification. Patient summaryAs opposed to immediate active treatment (surgery or radiation), active surveillance (AS) involves closely monitoring low-risk prostate cancers and only using active treatment if there are signs of progression. Our study is the first to suggest that obesity is associated with a higher risk of cancer progression while on AS. Further research is needed to determine if diet and exercise can decrease the risk of cancer progression while on AS.

Predicting progression in patients followed with active surveillance for low-risk prostate cancer.

38 Background: Due to the inability to predict progression and need for treatment, patients with low-risk prostate cancer (LRPC) managed by active surveillance (AS) are subjected to repeated biopsies and their possible complications. We developed a nomogram predicting the risk of progression in patients on AS for LRPC. Methods: A retrospective review of all patients enrolled in an AS program at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1993 and 2012 was conducted. Demographic, clinical, and pathologic data for patients who met the inclusion criteria for AS (cT1 or cT2a, prostate-specific antigen [PSA] less than 10, Gleason 6 or less, no more than three positive biopsy cores and no greater than 50% involvement of any single core) on the diagnostic and the confirmatory biopsies were collected and used to develop a nomogram for predicting progression-free probability. Multivariable logistic regression analysis was used to model the association between each risk variable (age, PSA levels, clinical stage, biopsy features) and disease progression. Progression was defined as failure to meet the inclusion criteria during follow up. Results: A total of 1,095 patients were enrolled in an AS program at MSKCC during the study period, of which 680 met the inclusion criteria for AS on both the diagnostic and the confirmatory biopsies and had available follow-up. At a median follow-up of 3 years 101 patients progressed. A nomogram predicting the progression-free probability was designed based on characteristics at diagnosis, result of a confirmatory biopsy and the number of negative and positive surveillance biopsies to date. A concordance index of 0.596 was calculated. Conclusions: Conditioned upon external validation, this nomogram can be used to counsel patients on their risk of progression and their surveillance protocol can be adjusted appropriately, possibly avoiding unnecessary biopsies and preventing biopsy-related complications.

Focal Therapy and Prostate Cancer

The International Task Force on Prostate Cancer defines focal therapy (FT) for prostate cancer (PCa) as the therapy that "selectively ablates known disease and preserves existing functions, with the overall objective of minimizing lifetime morbidity without compromising life expectancy". FT for the treatment of PCa has been called the "male lumpectomy", an analogue to women's breast lumpectomy for the treatment of breast cancer. Radical prostatectomy continues to be the most frequently performed treatment for localized PCa, as anatomic knowledge and several technical advances, i.e. the introduction of robotic assisted surgery, have led to successful oncological outcome and lower rates of post-treatment morbidity. However, a proportion of patients still experiences a no negligible sexual, urinary, and bowel morbidity. Although the rationale of active surveillance for low-risk PCa (PSA <10 ng/mL, Gleason grade 6 or less, and clinical stage T1c-T2a) is sound, only few of newly diagnosed patients elect this approach. Thus, in the recent years the concept of a "subtotal therapy" gained the interest of some urological schools. The aim of this paper is to review the existing literature in order to provide the status of art on FT for PCa. The manuscript will focus on the characteristics of the target population, on the pre-operative evaluation to localise disease, as well as on perioperative, functional, and disease-control following focal therapy.

Prostate Cancer and the Increasing Role of Active Surveillance

Prostate cancer (PC) is the most often diagnosed non-skin cancer and the second leading cause of cancer-related death among men in the United States. As a result, for many years the American Urological Association (AUA) and the American Cancer Society have issued statements recommending screening for PC, resulting in its widespread implementation in the United States. Recently, the United States Preventative Services Task Force gave PC screening a recommendation of D, that is, against PC screening for all men. The AUA countered this recommendation, stating that since the development of PC screening using prostate-specific antigen, a reduction in PC-specific mortality has been seen, and that the risk reduction occurred in a setting in which many of the patients were not aggressively treated for prostate cancer. Active surveillance may be described as a method to potentially delay or obviate the need for treatment in men with clinically insignificant PC or PC thought to be at low risk for progression. Studies have shown no significant difference in outcome or pathology between men with low risk PC who receive treatment at the point of progression and those undergoing immediate treatment. Ongoing studies are evaluating the efficacy and utility of active surveillance for low-risk PC. Interim results of these studies have shown that approximately 30% of patients progress on active surveillance. However, “progression” does not necessarily mean treatment failure; rarely do patients develop locally advanced or metastatic disease. Active surveillance has also been shown to be cost-effective when compared with immediate treatment for PC. Longer follow-up may continue to show an increased benefit of active surveillance as a reasonable initial approach to the management of men with low-risk, clinically localized PC.

Editorial Comment

The use of 5-ARIs in men undergoing active surveillance for low-risk PCa has been controversial. This study adds data that 5-ARI therapy could be beneficial. The results are consistent with those from the REDEEM trial in that a significant majority (75%) of men receiving 5-ARI had no evidence of pathologic cancer progression at the restaging biopsy after a median follow-up of 35 months. Active Surveillance of Very-low-risk Prostate Cancer in the Setting of Active Treatment of Benign Prostatic Hyperplasia With 5α-reductase InhibitorsUrologyVol. 81Issue 5PreviewTo review the efficacy of treating benign prostatic hyperplasia and very-low-risk prostate cancer (PCa) in patients receiving active surveillance and 5α-reductase inhibitor (5-ARI; finasteride or dutasteride) treatment. Full-Text PDF ReplyUrologyVol. 81Issue 5PreviewConsistent with the findings from the REDEEM trial, our outcomes suggest that 5-ARIs do not increase the risk of intermediate- or high-risk PCa (Gleason score 7-10) in men receiving active surveillance. Our study demonstrates only a small risk of progression to Gleason score 7 cancer on repeat biopsy. We believe this can be attributed to detection bias, as the gland volume reduction from 5-ARI therapy—along with the simple increase in total cumulative number of biopsy cores taken over time—enhances the clinician's ability to find higher grade PCa. Full-Text PDF

Ongoing Debate on the Management of Small Renal Masses: Should They Be Treated Like Low-Risk Prostate Cancers?

Ongoing Debate on the Management of Small Renal Masses: Should They Be Treated Like Low-Risk Prostate Cancers?

2138 PROSTATE-SPECIFIC ANTIGEN RISES FASTER IN PATIENTS WITH MULTIPLE NEGATIVE BIOPSIES COMPARED TO PATIENTS FOLLOWED BY ACTIVE SURVEILLANCE FOR LOW-RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20102138 PROSTATE-SPECIFIC ANTIGEN RISES FASTER IN PATIENTS WITH MULTIPLE NEGATIVE BIOPSIES COMPARED TO PATIENTS FOLLOWED BY ACTIVE SURVEILLANCE FOR LOW-RISK PROSTATE CANCER Akshat C. Pujara, Andrew J. Stephenson, Ranko Miocinovic, Ryan K. Berglund, and J. Stephen Jones Akshat C. PujaraAkshat C. Pujara More articles by this author , Andrew J. StephensonAndrew J. Stephenson More articles by this author , Ranko MiocinovicRanko Miocinovic More articles by this author , Ryan K. BerglundRyan K. Berglund More articles by this author , and J. Stephen JonesJ. Stephen Jones More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2226AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate-specific antigen (PSA) is historically used as a marker of disease progression in most prostate cancer (PCa) active surveillance (AS) protocols without evidence of its utility. We compared PSA dynamics in AS patients to patients with similar clinical findings who had at least two prior negative biopsies and are unlikely to have prostate cancer. METHODS Data were collected from a prospective database and chart review. AS patients were defined as those having favorable clinical features and biopsy parameters at diagnosis and repeat biopsy confirming low-risk disease. The control group consisted of patients considered to have no known disease by virtue of at least two prior negative biopsies. Patients were matched by age (5 year increments), PSA (1 ng/ml increments), BMI (increments of 5), gland volume (20 cm3 increments) at diagnostic or first negative biopsy, respectively, and race. PSA values were adjusted for 5-alpha reductase inhibitor use. RESULTS From February 2000 to August 2009, 99 men were followed by AS for low-risk PCa. Of these, 46 could be matched to 53 of 434 men in the control group. At diagnostic biopsy (AS) and first negative biopsy (control), mean age was 68 ± 7 and 64 ± 6 years, mean PSA 5.84 ± 3.71 and 5.19 ± 1.67 ng/ml, mean BMI 28 ± 4 and 28 ± 4, and mean gland volume 47 ± 24 and 45 ± 13 cm3, respectively. Median interval from diagnosis to last PSA was 1.3 years (IQR 0.9 - 1.7) in AS patients and from first negative biopsy to last PSA 1.6 years (IQR 1.1 - 2.3) in the control group. Median PSA doubling time was 4.6 years (IQR 2.4 - 10.3) in AS patients and 4.31 years (IQR 2.8 - 7.0) in the control group. Median PSA velocity was 0.62 ng/ml/year (IQR 0.60 - 0.68) in AS patients and 1.63 ng/ml/year (IQR 0.79 - 2.59) in the control group (Figure 1). CONCLUSIONS PSA dynamics in patients with multiple negative PSA-triggered biopsies reflect a more rapidly rising PSA than in AS patients over short term-intervals. This finding calls into question the value of using PSA changes to follow patients on AS. Routine surveillance biopsy or magnetic resonance imaging may be warranted in AS patients regardless of PSA. Longer follow-up is required to further evaluate PSA dynamics in AS patients and implications for disease management. Cleveland, OH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e831 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akshat C. Pujara More articles by this author Andrew J. Stephenson More articles by this author Ranko Miocinovic More articles by this author Ryan K. Berglund More articles by this author J. Stephen Jones More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Focal Targeted Therapy Will Be a Future Treatment Modality for Early Stage Prostate Cancer

Focal targeted therapy of early stage prostate cancer (PCa) can ideally facilitate the concept of personalized medicine in contemporary surgical oncology. To present indications and outcomes of subtotal glandular ablation. This treatment approach aims at the elimination of the cancer with preservation of uninvolved tissue in an attempt to maintain a patient's quality of life (QoL), including undisturbed erectile function as well as urinary and bowel control. In 2002, the idea of a “lumpectomy” using an organ-sparing approach for very localized PCa was proposed in parallel with organ-sparing breast cancer treatment in women. Since then, a few pilot clinical studies have demonstrated an acceptable short-term cancer control while minimizing the complication rate. At the same time, progress in PCa screening has led to a significant stage and tumor volume migration toward early stage disease. In the past few years, a collection of accumulated data has created a scientific background for further development of this concept toward a wider implementation into clinical practice. In this paper, we review all available literature from PubMed of the past 15 yr—from 1994 to 2008—including the terms localized prostate cancer, focal therapy, organ preservation, and morbidity. Several factors were identified that need to be taken into account to further develop an organ-sparing treatment approach for early stage localized PCa and turn this concept into clinical practice. First, novel thermoablative techniques such as third-generation cryosurgery, high-intensity focused ultrasound (HIFU), vascular photodynamic therapy and, electroporation can precisely target a tumor lesion within the prostate while maintaining the integrity of the surrounding tissues. Second, new ultrasound, magnetic resonance imaging (MRI) and molecular imaging techniques may provide new means to detect small PCa lesions. Third, extended image-guided biopsy protocols using a transperineal rather than a transrectal approach can provide a more exact spatial distribution of PCa lesions within the prostate. Fourth, careful patient selection using an individualized approach is a prerequisite for optimal preoperative planning and a successful treatment outcome. For patients with early stage localized PCa limited to one focus or lobe and who express a great desire not to jeopardize their QoL, targeted focal therapy will likely play a more significant role in the future as a tangible treatment option. Moreover, focal therapy may fill the gap between active surveillance for low-risk PCa and radical treatment for higher-risk forms. Focal targeted therapy is becoming an attractive and tangible treatment option for patients with early stage localized prostate cancer limited to one focus or lobe and who are interested in maintaining a higher quality of life.