Original article
Pathologic outcomes for low-risk prostate cancer after delayed radical prostatectomy in the United States

https://doi.org/10.1016/j.urolonc.2014.12.012Get rights and content

Abstract

Objectives

To measure adverse pathologic outcomes following radical prostatectomy (RP) for men with low-risk prostate cancer in the United States based on time from diagnosis to surgery.

Methods

We extracted data from the National Cancer Database in 2010 and 2011 on 17,943 low-risk patients (Gleason score = 3+3, prostate-specific antigen <10 ng/ml, and cT1–T2) who underwent RP. We identified men who delayed RP by>6 months after diagnosis and measured the effect of delayed RP on pathologic upgrading, upstaging, nodal metastases, and positive surgical margins.

Results

Overall, 16,818 underwent RP≤6 months, 894 at 6 to 9 months, 169 at 9 to 12 months, and 62 at>12 months from diagnostic biopsy. Furthermore, upgrading occurred in 43%, upstaging in 9%, positive surgical margins in 16%, and nodal metastases in 0.3% of men. Upgrading, upstaging, or nodal metastases occurred in 45% of men. On multivariable analysis, higher prostate-specific antigen (4.1–9.9 ng/ml vs. 0.1–2.4 ng/ml; odds ratio [OR] = 1.87, 95% CI: 1.66–2.10),>2 positive biopsy cores (OR = 1.68, 95% CI: 1.57–1.81),≥34% positive biopsy cores (OR = 1.28, 95% CI: 1.18–1.39), black race (OR = 1.16, 95% CI: 1.05–1.28), and time from biopsy to RP>12 months (vs.≤6 mo: OR = 1.70, 95% CI: 1.01–2.84) each independently increased the composite risk of adverse pathology (all P< 0.05).

Conclusion

In the United States, nearly half of men with low-risk prostate cancer experience at least one adverse pathologic outcome at RP. Delaying RP up to 12 months did not change the risk of adverse pathology. Men may safely use the time following their initial biopsy to consider management options and obtain a restaging biopsy, if recommended.

Introduction

Recent population-based data from Sweden suggest 50% of Swedish men with low-risk prostate cancer (PCa) experience either upgrading or upstaging at radical prostatectomy (RP) [1]. However, similar studies from the United States have been limited to small low-risk cohorts (largest n = 771) mostly at large academic institutions, making the findings difficult to generalize to the overall national population [2].

An option for men with low-risk PCa, active surveillance, is a strategy intended to optimize quality of life without compromising long-term oncologic efficacy [3]. Through 2004, fewer than 10% of qualifying patients elected this approach [4]. Commonly attributed to patient choice, uncertainty over long-term results of active surveillance, or anxiety, the decision to undergo initial surgery or radiation therapy can also be due to perceptions surrounding delaying definitive treatment [5].

Patients delaying definitive treatment is expected to increase in the United States with recent guidelines recommending active surveillance as an option for low-risk men [6], [7] and a recent rise in the use of conservative management strategies in the United States [8]. However, studies in the United States investigating the safety and short-term outcomes of delayed RP for men with low-risk PCa have had conflicting results. A single surgeon series [9] and data from Toronto [10] demonstrated increased risk of adverse pathologic findings in men who delayed RP. However, results from University of California, San Francisco [11], 5 Veterans Affairs Medical Centers [12], Memorial Sloan Kettering Cancer Center [13], and Johns Hopkins [14] suggest delaying RP does not appear to affect outcomes. Each of these studies was limited by a relatively small number of patients who delayed RP between 6 and 12 months.

To more broadly analyze this topic, we used the National Cancer Database (NCDB) to measure the proportions of patients with low-risk PCa with Gleason upgrading, upstaging, nodal metastases, and positive surgical margins at RP. We compared these adverse pathologic outcomes based on multiple variables, including time from diagnosis to RP.

Section snippets

Materials and methods

We extracted our study population from the NCDB PCa participant user file. The NCDB is a registry of more than 1,400 hospitals with accredited cancer programs approved by the America College of Surgeons׳ Commission on Cancer and the America Cancer Society [15]. Beginning in 2010, the NCDB started recording clinical and pathologic Gleason patterns. From 2010 to 2011, we identified all patients with PCa who had nonmetastatic PCa as their first and only cancer (cM0 and cN0/x: n = 186,816). From

Results

Among men with biopsy details, 16,818 underwent RP within 6 months of diagnosis. Of the men who delayed RP, 894 (5%), 169 (0.9%), and 62 (0.3%) delayed it by 6 to 9 months, 9 to 12 months, and greater than 12 months, respectively (Table 1). These groups were similar based on age, comorbidities, pretreatment PSA, and total number of biopsy cores. Men who delayed RP were more likely to be black (P = 0.013), undergo treatment at an academic facility (P<0.001), have cT1 disease (P = 0.03), have<3

Discussion

We used retrospective, population-based data from the NCDB to derive the largest contemporary cohort of men who delayed RP for low-risk PCa. Our study is the first to our knowledge reporting population-based rates of adverse pathologic outcomes in the United States among guideline-determined low-risk men based on time from diagnosis to surgery [6], [7]. Similar to data from Sweden and other single institutions, we found nearly half of low-risk men in the United States experience at least one

Conclusions

In the United States, nearly half of men with low-risk PCa experience at least one adverse pathologic outcome at RP. Delaying RP up to 12 months did not increase the risk of adverse pathology. Men may safely use the time following their initial biopsy to consider management options and obtain a restaging biopsy, if recommended.

References (29)

  • A.C. Reese et al.

    Minimal impact of clinical stage on prostate cancer prognosis among contemporary patients with clinically localized disease

    J Urol

    (2010)
  • S.J. Freedland et al.

    Comparison of percentage of total prostate needle biopsy tissue with cancer to percentage of cores with cancer for predicting PSA recurrence after radical prostatectomy: results from the SEARCH database

    Urology

    (2003)
  • L. Klotz et al.

    Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer

    J Clin Oncol

    (2010)
  • D.A. Barocas et al.

    What percentage of patients with newly diagnosed carcinoma of the prostate are candidates for surveillance? An analysis of the CaPSURE database

    J Urol

    (2008)
  • Cited by (24)

    • Low-risk Prostate Cancer: Identification, Management, and Outcomes

      2017, European Urology
      Citation Excerpt :

      Although upstaging and upgrading rates were lower in very low-risk PCa when compared with low-risk PCa, the risk of harboring adverse pathologic features is still considerable. Weiner et al [29] evaluated the impact of delayed RP (untreated for a minimum of 6 mo) in 17 943 low-risk PCa patients and found half of patients experienced at least one adverse pathologic outcome at RP specimen, although delaying RP up to 12 mo did not change the risk of adverse pathology. Auffenberg et al [34] recently evaluated 2858 low-risk PCa patients from practices in Michigan Urological Surgery Improvement Collaborative.

    • Risk of Pathological Upgrading and Up Staging among Men with Low Risk Prostate Cancer Varies by Race: Results from the National Cancer Database

      2017, Journal of Urology
      Citation Excerpt :

      In 2 prior NCDB studies it was incidentally observed that AA race was associated with UGUS, consistent with our findings. Weiner et al analyzed the effect of delayed RP in low risk cases and found that AA race was associated with 1.2-fold higher odds of UGUS (p <0.001, sample size 26,884).11 In a report on the effect of comorbidity in low risk cases Maurice et al similarly found that nonwhite race was associated with 1.1-fold higher odds of UGUS (p=0.001, sample size 29,447).12

    • What is the best way not to treat prostate cancer?

      2017, Urologic Oncology: Seminars and Original Investigations
      Citation Excerpt :

      In a series of patients treated at UCSF after initial management with AS, those undergoing delayed prostatectomy had similar rates of adverse pathology compared with similarly matched controls [89]. Rates have also appeared equivalent in larger, population-level studies with delays of 12 months from diagnosis [90]. Nonetheless, patients and providers must be aware that some degree of risk is associated with deferment of treatment, as are evidences by rare, yet observed occurrences of metastatic progression during surveillance highlighting the need for shared decision-making.

    View all citing articles on Scopus

    Mr. Weiner was supported by the Urology Care Foundation and the Herbert Brendler, M.D., Summer Medical Student Fellowship. The funding support had no role in the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit the manuscript for publication.

    View full text