Abstract
Background/Aim: To evaluate the diagnosis and management of prostate cancer (PCa) across twenty years of clinical practice. Materials and Methods: From January 2000 to January 2019, 7,000 patients underwent transperineal prostate biopsy and 990 went through radical prostatectomy, respectively. The clinical and pathological stage in the presence of prostate cancer (PCa) are reported here. Results: The overall number of biopsies increased over time from 1,500 (years 2000-2005) to 2,150 (years 2015-2019). PCa was found in 2,500/7,000 (37.7%) patients while the diagnosis of very low risk PCa increased from 3.2% to 13.6% and diagnosis of metastatic PCa decreased from 12% to 4%. A greater number of men with locally advanced/oligometastatic PCa underwent surgery over time with increasing numbers of nodal involvement and positive surgical margins from 5.4% and 27.2% to 10.8% and 35.6%, respectively. Conclusion: Overtreatment of PCa has been reduced over time by establishing Active Surveillance protocols. Additionally, the multidisciplinar approach has improved the management of locally advanced/oligometastatic PCa.
- Prostate cancer
- MRI and prostate cancer
- MRI/TRUS targeted prostate biopsy
- transperineal prostate biopsy
- radical retropubic prostatectomy
Prostate cancer (PCa) is the most common type of cancer with more than 360,000 deaths per year (1), however the estimated risk of overdiagnosis from the screening protocols is equal to 50% (2). These facts highlight the necessity to separate the cases of clinically-significant prostate cancer (csPCa) from those of indolent tumors (3). During the last decade, active surveillance (AS) has become an alternative (4, 5) to radical treatment of low/very low risk PCa, focusing on the prevention of over-treating patients as well as on the strict monitoring over time. This has helped establish potential benefits of re-classification, which can justify the deferred radical treatment. In this respect, multiparametric magnetic resonance imaging (mpMRI) has been recommended for the diagnosis of csPCa in men who are candidates for prostate biopsy (6) and/or are enrolled in AS protocols (5). Finally, through a multidisciplinary approach, the introduction of robotic radical prostatectomy (RALP) in the clinical practice, advanced radiotherapy strategies, focal therapy combined with new oncological drugs, have improved the outcome of PCa patients in each clinical stage.
Here, we report the progress in the diagnosis and management of men with PCa accross twenty-years of clinical practice focusing on the clinical presentation and therapeutic strategies.
Patients and Methods
Patients. From January 2000 to January 2019, 7,000 men aged between 38 and 91 years (median age=61.8 years) underwent prostate biopsy under the suspicion of PCa. The indications for biopsy were: i) abnormal digital rectal examination, ii) PSA >10 ng/ml or iii) PSA values between 4.1-10 ng/ml, and 2.6-4 ng/ml with Free/Total PSA≤25% and ≤20%, respectively.
Methods. Prostate biopsy was performed transperineally using a freehand technique, a tru-cut 18-gauge needle (Bard; Covington, GA) and a GE Logiq 500 PRO ecograph (General Electric; Milwaukee, WI) supplied with a biplanar transrectal probe (5-6.5 MHz). In the case of an initial or a repeat procedure an extended (18 cores) vs. a saturation biopsy (SPBx: 24 cores) was done under local anaesthesia or sedation accompanied by antibiotic prophylaxis (one tablet daily of levofloxacin 500 mg for 3 days) (7). Since 2011, 1,350 candidate patients for repeat biopsy were submitted to mpMRI. In the presence of a PI-RADS (Prostate Imaging-Reporting and Data System–version 2) score≥3, a transperineal mpMRI/TRUS fusion biopsy (TPBx: 4 cores for each suspicious area) was added to SPBx (6). All mpMRI examinations were performed using a 3.0 Tesla scanner, (ACHIEVA 3T; Philips Healthcare Best, the Netherlands) equipped with: i) a 16-channel phased-array coil placed around the pelvic area with the patient in the supine position, ii) a multi-planar turbo spin-echo T2-weighted, iii) an axial diffusion weighted imaging and iv) an axial dynamic contrast enhanced MRI (8). The TPBx was performed transperineally using a tru-cut 18-gauge needle (Bard; Covington, GA, USA) using a Hitachi 70 Arietta ecograph, (Chiba, Japan) supplied with a bi-planar transrectal probe (6). All the data were collected using the START criteria (9).
All the patients with csPCa and a life expectancy greater than ten years were candidates for definitive treatment (radical prostatectomy or external beam radiation). Since 2013, men with very low risk PCa were enrolled in an Active Surveillance protocol (10).
The diagnosis and management of PCa was evaluated across twenty-years (subdivided in four periods of 5 years (i) 2000-2004, ii) 2005-2009, iii) 2010-2014 and iv) 2015-2019 of clinical practice at a single Center, following the new diagnostic (i.e., mpMRI) and therapeutic (i.e., AS) strategies. In detail, biopsies and definitive specimens of men submitted to prostate biopsy and radical retropubic prostatectomy (RRP) showed changes in clinical and pathological stages over time. The Clavien-Dindo grading system for the classification of biopsy and surgery complications was used (11).
Statistics. For our statistical analysis we used the t Student's - test with a p-value<0.05 as statistically significant.
Results
The number of prostate biopsies and the detection rate for PCa increased over time (Table I) from 1,500 (years 2000-2005) to 2,150 (years 2015-2019) (p=0.01). On the contrary, the incidence of complications following transperineal prostate biopsy was limited during the twenty-year assessment period with respect to the number of needle cores, the number of patients with sepsis and those who needed hospital admission. In addition, only 46/7000 (0.6%) and 28/7000 (0.4%) were assigned a grade II and I of the Clavien-Dindo complications scale, respectively. The number of patients who were admitted to the emergency department was limited to 9.3% (140/1500 patients) during the period 2000-2004) and 9.5 % (905/2150) during the period 2015-2019.
The overall detection rate of PCa significantly increased from 30.6% (years 2000-2004) to 38.6% (years 2015-2019) (p=0.03); in detail, the diagnosis of low-versus intermediate- versus high-risk versus metastatic PCa (12) is reported in Table I. The incidence of clinical T1c PCa increased from 62 (years 2000-2004) to 69% (years 2015-2019) (p=0.03). Conversely, the diagnosis of metastatic PCa significantly decreased from 12% to 4% (p=0.01). The detection rate of very low-risk PCa significantly increased from 3.2% (26/285 cases) to 13.6% (79/572 cases) (p=0.01); therefore, since 2013, about 30 men/year were enrolled in an AS (11) protocol with a risk of upgrading/upstaging at confirmatory biopsy equal to 28%.
Among the 1,480 men candidate to definitive treatment, 490 (31%) underwent external beam radiation and 990 (69%) were submitted to RRP (Table II). The median age of men who underwent surgery progressively increased from 65.2 (range=42-71 years, period 2000-2004) to 68.3 years (range=41-79 years; period 2015-2019). The incidence of indolent PCa decreased from 3.6% (years 2000-2004) to 1% (years 2015-2019). On the contrary, a greater number of locally advanced and oligometastatic PCa, affecting manly younger men, was submitted to surgery. In fact, pT3b stage (13), nodal involvement and positive surgical margins significantly increased from 13.2%, 5.4% and 27.2% (years 2000-2004) to 18.4% (p=0.06), 10.8% (p=0.04) and 35.6% (p=0.01) (years 2015-2019), respectively (Table II). The number of nerve sparing procedures was limited during the period we evaluated because a greater number of men with very low risk PCa were included in AS protocols. The median time of surgery decreased from 150 (range=120-210 minutes) to 120 minutes (90-150 minutes) and was correlated with the surgical template used to remove the nodes. At the same time, the number of the removed nodes increased from 8 (range=2-10 nodes in the years 2000-2004) to 18 (range=9-34 nodes in the years 2015-2019) according to the PCa clinical stage.
The incidence of complications 90 days post operation following RRP was also limited over time (Table III) while, the median blood loss decreased from 420 ml (range=50-1900 ml, years 2000-2004) to 350 ml (range=50-1100 ml, years 2015-2019).
Discussion
During the last decade the diagnosis and treatment of PCa has drammatically changed enacting on reducing the risk of overdiagnosis and overtreatment (14). Active Surveillance protocols (15) have significantly reduced the risk of overtreatment in men with low-risk PCa, prooving relatively safe, during long term follow-up offering a good prognosis including men with progressive disease (upgrading or upstaging). In addition, the clinical approach for treating locally advanced and/or oligometastatic PCa (16-18) in younger men has changed due to the multidisciplinar approach methods that seems to improve life aspettancy (19). In fact, a more accurate clinical stadiation using diagnostic imaging (i.e., Gallium-68 prostate-specific membrane antigen PET/TC or whole body MRI) (20) allows for a better selection of candidate patients for a sequential multidisciplinary approach instead of submitting them to aggressive surgery involving extended limphadenectomy as a first step of treatment (21, 22). At the same time, new radiotherapy strategies (23) implemented as initial, adjuvant or salvage teatments seems to improve the overall survival of the patients reducing the morbidity associated with radiotherapy. In addition, hormonal treatment (24) combined with chemotherapy (25) has demonstrated a favorable impact on the presence of metastatic PCa at diagnosis and of clinical progression. In conclusion, the therapeutic advances in the clinical management of PCa in all the clinical stages allow for a tailored treatment using a multidisciplinary approach, in the context of a dedicated Prostate Cancer Unit (26).
Detection rate for prostate cancer (PCa) in 7,000 men submitted to transperineal prostate biopsy during a twenty-year period (subdivided in 4 periods).
Pathological staging of 990 men submitted to radical retropubic prostatectomy (RRP) during a twenty-year period (subdivided in 4 periods).
Post-operative complications following radical retropubic prostatectomy (RRP) during a twenty-year period (subdivided in 4 periods).
In our series, which refer to 7,000 prostate biopsies and 990 RRP, during twenty-years of clinical practice we have reported the safety of the transperineal prostate biopsy with an estimated risk of sepsis equal to zero. This result should be taken into consideration in clinical practice due to the increased antibiotic resistance and the considerable risk of sepsis in men submitted to transrectal biopsy (27, 28). The overall number of prostate biopsies significantly increased over time from 1,500 (years 2000-2004) to 2,150 (years 2015-2019), the diagnosis of very low risk PCa significantly increased from 3.2% (26/285 cases) to 13.6% (79/572 cases) and, at the same time, metastatic PCa significantly decreased from 12% to 4%, in accordance with the results of the screening protocols. At the same time, the number of RRP decreased progressively, while a greater number of yourger men with locally advanced/oligometastatic PCa were submitted to surgery over time. In detail, pT3b stages, nodes involvement and positive surgical margins increased from 13.2%, 5.4% and 27.2% (years 2000-2004) to 18.4%, 10.8% and 35.6% (years 2015-2019), respectively. In addition, the number of nodes removed increased from 8 (rage: 2-10 nodes, years 2000-2004) to 18 (range: 9-34 nodes, years 2015-2019) depending on the clinical stage of the patient.
Regarding our results some considerations should be made. Firstly, the study is retrospective. Secondly, the surgical approach refers only to open RRP because in our Hospital we do not possess a robotic platform. Interestingly, this means that the study reflects the real clinical pratice of many geographic areas where minimally invasive surgery (RALP) cannot yet be performed (29, 30). Finally, the execution of RRP could have been selected for a greater number of locally advanced/oligometastatic PCa patients, while low- and intermediate-risk PCa patients suitable for nerve-sparing surgery were referred for a RALP approach.
The management of PCa needs a tailored approach to improve the patient's quality of life. In our twenty years of experience, the risk of over-treatment has been reduced by establishing AS protocols, while at the same time, the multidisciplinary approach has significantly improved the management of locally advanced/oligometastatic PCa.
Footnotes
Authors' Contributions
The Authors contributed equally to this article.
Conflicts of Interest
The Authors declare no conflict of Interest exists in regard to this study.
- Received January 15, 2019.
- Revision received January 29, 2019.
- Accepted February 5, 2019.
- Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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