Serial Prostate Biopsy and Histological Inflammation
Serial Prostate Biopsy and Histological Inflammation
Of the 604 men enrolled under our AS protocol during the study period, 133 had diagnostic biopsies performed at UCSF. Of these, 79 men had complete sets of slides available for rereview. Fifty-six men who underwent two or more biopsies and met inclusion criteria formed the study cohort. A total of 191 biopsies and 1327 cores were reviewed and inflammation was scored. Patients who met inclusion criteria did not differ from those excluded based on demographics or disease features (race, PSA, PSAV, clinical T-stage, GS, clinical risk group, number of biopsies and months of follow-up) with the exception of age. Men included were younger (mean age 62 years) compared with men excluded (mean age 66 years), P<0.01 (data not shown).
Demographic and baseline clinical data are summarized in Table 1. Forty (71%) were clinical stage T1c, 44 (79%) had PSA ≤10 ng ml and 55 (98%) had diagnostic GS≤6. No patients were identified as having symptomatic prostatitis within 6 months preceding entry into the AS program. Thirty-one (55%) had known BPH and 17 (30%) were on long-term nonsteroid anti-inflammatory therapy (that is, aspirin, ibuprofen) at study entry. Mean follow-up was 64.1 (±26.5) months. Twenty men (36%) had a total of two biopsies, 10 (18%) had three biopsies, 14 (25%) had four biopsies and 12 (21%) had five or more biopsies. Biopsies were performed at mean time intervals of 19 (±13) months (median 16.5, range 2–71, months), guided by surveillance protocol.
Average AI was 0 or very mild with overall score of 0.14 (±0.20). Maximum AI scores were distributed as 52% with no (score=0), 43% with mild (1), 4% with moderate (2) and 1% with severe (3) inflammation. Maximum AI by total number of biopsies and biopsy sequence are shown in Figure 1. Maximum AI score remained between 0 and 1 regardless of total biopsy exposure.
(Enlarge Image)
Figure 1.
Acute inflammation (AI) across biopsies.
Similarly, the overall average CI score was low at 0.46 (±0.46). Maximum CI score was the most pronounced as 19% had no, 46% had mild, 28% had moderate and 7% had severe inflammation. Maximum scores by total number of biopsies and biopsy sequence are shown in Figure 2. Maximum CI score at diagnosis was between 1 and 2 for those with one to four biopsies and below 1 for those with five biopsies (N=12).
(Enlarge Image)
Figure 2.
Chronic inflammation (CI) across biopsies.
Adjusted average and maximum AI and CI scores are presented in Figure 3. After adjusting for age, prostate volume, clinical risk and BPH, there was no statistically significant change in AI across successive biopsies. Conversely, average CI scores slightly increased with increasing number of biopsies (nonsignificant, P=0.08) and maximum CI scores demonstrated a small, though significant, increase with each successive biopsy (P=0.04). Median PSAV during study period was 0.06 (interquartile range −0.31, 0.49). No correlation was seen between PSAV and total biopsy number (Pearson's R=−0.02, P=0.87).
(Enlarge Image)
Figure 3.
Adjusted average and maximum acute (AI) and chronic inflammation (CI) by biopsy sequence. NSAID, nonsteroidal anti-inflammatory.
Nineteen (34%) men experienced a GS upgrade from ≤6 at diagnosis, with 11 (56%) of these occurring at second biopsy. Of those with grade progression, 14 (74%) increased to 3+4, two (4%) to 4+3, two (4%) to 4+4 and one to 5+4. The majority of men (82%) had CI on diagnostic biopsy and these men had a slightly higher rate of grade progression compared with those without baseline CI (35% vs 30%). Mean CI scores (average, maximum) with each successive biopsy were not statistically different in men with grade progression vs without grade progression (data not shown). Location of CI in last (or upgraded) biopsy relative to cancer core(s) is presented in Table 2. CI was located within the same core in 5 (26%) of those with grade progression and 10 (27%) of those without progression (P=0.26).
Treatment-free survival was 56% at 5 years with 25 men eventually undergoing definitive treatment. Of these, treatment was triggered by grade progression in 13 (52%) patients, volume progression in 3 (12%), PSA progression in 2 (8%) and patient choice in 7 (28%). Radical prostatectomy was performed in 22 (88%) and 3 (12%) had radiation therapy. Of the patients with biopsy upgrade, 10 (53%) underwent radical prostatectomy, 2 (10%) underwent radiation therapy and 7 (37%) elected no treatment to date.
Results
Of the 604 men enrolled under our AS protocol during the study period, 133 had diagnostic biopsies performed at UCSF. Of these, 79 men had complete sets of slides available for rereview. Fifty-six men who underwent two or more biopsies and met inclusion criteria formed the study cohort. A total of 191 biopsies and 1327 cores were reviewed and inflammation was scored. Patients who met inclusion criteria did not differ from those excluded based on demographics or disease features (race, PSA, PSAV, clinical T-stage, GS, clinical risk group, number of biopsies and months of follow-up) with the exception of age. Men included were younger (mean age 62 years) compared with men excluded (mean age 66 years), P<0.01 (data not shown).
Demographic and baseline clinical data are summarized in Table 1. Forty (71%) were clinical stage T1c, 44 (79%) had PSA ≤10 ng ml and 55 (98%) had diagnostic GS≤6. No patients were identified as having symptomatic prostatitis within 6 months preceding entry into the AS program. Thirty-one (55%) had known BPH and 17 (30%) were on long-term nonsteroid anti-inflammatory therapy (that is, aspirin, ibuprofen) at study entry. Mean follow-up was 64.1 (±26.5) months. Twenty men (36%) had a total of two biopsies, 10 (18%) had three biopsies, 14 (25%) had four biopsies and 12 (21%) had five or more biopsies. Biopsies were performed at mean time intervals of 19 (±13) months (median 16.5, range 2–71, months), guided by surveillance protocol.
Average AI was 0 or very mild with overall score of 0.14 (±0.20). Maximum AI scores were distributed as 52% with no (score=0), 43% with mild (1), 4% with moderate (2) and 1% with severe (3) inflammation. Maximum AI by total number of biopsies and biopsy sequence are shown in Figure 1. Maximum AI score remained between 0 and 1 regardless of total biopsy exposure.
(Enlarge Image)
Figure 1.
Acute inflammation (AI) across biopsies.
Similarly, the overall average CI score was low at 0.46 (±0.46). Maximum CI score was the most pronounced as 19% had no, 46% had mild, 28% had moderate and 7% had severe inflammation. Maximum scores by total number of biopsies and biopsy sequence are shown in Figure 2. Maximum CI score at diagnosis was between 1 and 2 for those with one to four biopsies and below 1 for those with five biopsies (N=12).
(Enlarge Image)
Figure 2.
Chronic inflammation (CI) across biopsies.
Adjusted average and maximum AI and CI scores are presented in Figure 3. After adjusting for age, prostate volume, clinical risk and BPH, there was no statistically significant change in AI across successive biopsies. Conversely, average CI scores slightly increased with increasing number of biopsies (nonsignificant, P=0.08) and maximum CI scores demonstrated a small, though significant, increase with each successive biopsy (P=0.04). Median PSAV during study period was 0.06 (interquartile range −0.31, 0.49). No correlation was seen between PSAV and total biopsy number (Pearson's R=−0.02, P=0.87).
(Enlarge Image)
Figure 3.
Adjusted average and maximum acute (AI) and chronic inflammation (CI) by biopsy sequence. NSAID, nonsteroidal anti-inflammatory.
Nineteen (34%) men experienced a GS upgrade from ≤6 at diagnosis, with 11 (56%) of these occurring at second biopsy. Of those with grade progression, 14 (74%) increased to 3+4, two (4%) to 4+3, two (4%) to 4+4 and one to 5+4. The majority of men (82%) had CI on diagnostic biopsy and these men had a slightly higher rate of grade progression compared with those without baseline CI (35% vs 30%). Mean CI scores (average, maximum) with each successive biopsy were not statistically different in men with grade progression vs without grade progression (data not shown). Location of CI in last (or upgraded) biopsy relative to cancer core(s) is presented in Table 2. CI was located within the same core in 5 (26%) of those with grade progression and 10 (27%) of those without progression (P=0.26).
Treatment-free survival was 56% at 5 years with 25 men eventually undergoing definitive treatment. Of these, treatment was triggered by grade progression in 13 (52%) patients, volume progression in 3 (12%), PSA progression in 2 (8%) and patient choice in 7 (28%). Radical prostatectomy was performed in 22 (88%) and 3 (12%) had radiation therapy. Of the patients with biopsy upgrade, 10 (53%) underwent radical prostatectomy, 2 (10%) underwent radiation therapy and 7 (37%) elected no treatment to date.
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