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Background Presence of small (tertiary) Gleason 5 pattern is linked to a higher risk of biochemical recurrence in prostate cancer. It is unclear, however, how to integrate small Gleason 5 elements into clinically relevant Gleason grade groups. Objective To analyze the prognostic impact of Gleason 5 patterns in prostate cancer and to develop a method for integrating tertiary Gleason 5 patterns into a quantitative Gleason grading system. Design, setting, and participants Prostatectomy specimens from 13 261 consecutive patients and of 3295 matched preoperative biopsies were available. Percentages of Gleason 3, 4, and 5 had been recorded for each cancer. Outcome measurements and statistical analysis: Results and limitations Our data demonstrate that minimal Gleason 5 areas have strong prognostic impact in Gleason 7 carcinomas, while further expansion of the Gleason 5 pattern population has less impact. We thus defined an integrated quantitative Gleason score (IQ-Gleason) by adding a lump score of 10 to the percentage of unfavorable Gleason pattern (Gleason 4/5) if any Gleason 5 was present and by adding another 7.5 points in case of a Gleason 5 fraction >20%. There was a continuous increase of the risk of prostate-specific antigen recurrence with increasing IQ-Gleason. This was also true for subgroups with identical Cancer of the Prostate Risk Assessment Postsurgical scores ( p p Conclusions The IQ-Gleason represents a simple and efficient approach for combining both quantitative Gleason grading and tertiary Gleason grades in one highly prognostic numerical variable. Patient summary Prostatectomy specimens (13 261) were analyzed to estimate the relevance of small Gleason 5 elements in prostate cancers. Even the smallest Gleason 5 areas markedly increased the risk of prostate-specific antigen recurrence after surgery. Larger fractions of Gleason 5 patterns had less further impact on prognosis. Based on this, a numerical Gleason score (integrated quantitative Gleason score) was defined by the percentages of Gleason 4 and 5 patterns, enabling a refined estimate of patient prognosis.

Background Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤6, 3+4, 4+3, 8, and 9–10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5–45% in a Gleason 3+4=7 cancer. Objective To assess the clinical relevance of the fractions of Gleason patterns. Design, setting, and participants Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. Outcome measurements and statistical analysis To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Results and limitations Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Conclusions Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Patient summary Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤3+3, 3+4, 4+3, 8, 9–10. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.

Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete.To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice.Retrospective analysis of pathological and clinical data from 14 528 consecutive patients.Radical prostatectomy.The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint.Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p0.0001). Both N1 and L1 were linked to PSA recurrence (p0.0001 each). This was also true for 17 patients with isolated tumor cells (ie,200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients.Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence.Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.