AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2639-4162/016
*Corresponding Author: Grimar de Oliveira Paula, Study undertaken in the Department of Cytopathology and Anatomical Pathology and Urology of the Federal District Base Institute (NUCAP-IHBDF), Brasília, Brazil.
Citation: Grimar de Oliveira Paula, João Emerson de Alencar Santos, Luiz Carlos de Araújo Souza. Analysis of the Prevalence and Factors Related to Biochemical Relapse in Patients Undergoing Radical Prostatectomy with Lymphadenectomy J. General Medicine and Clinical Practice . DOI: 10.31579/2639-4162/016
Copyright: © 2019 Grimar de Oliveira Paula. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 16 February 2019 | Accepted: 15 March 2019 | Published: 23 March 2019
Keywords: Prostate Specific Antigen ; Biochemical Recurrence ; Prostate Cancer
Objectives - Analyze the prevalence of biochemical recurrence (BCR) in patients submitted to radical prostatectomy with lymphadenectomy (RP-LD) the most prevalent clinical and pathological staging in the BCR and to correlate the sum of the Gleason score (GS) in the surgical specimen in patients who presented BCR. Method - Analysis of 100 patients diagnosed with prostate adenocarcinoma who performed RP-LD between 2013 to 2017. All subjects underwent transrectal prostate biopsy due to PSA or rectal examination and RP-LD. The lymphadenectomy considered in the study was the iliac-obturator, and the surgical pieces were analyzed to determine the pathological staging and its descriptors. All patients who had two or more PSA measurements >0.2 ng/ml and who had undergone RP-LD were considered postoperative. Results -About 22% of the patients submitted to RP-LD presented BCR. Patients with BCR had a 59-76 age range, mean age of 66.27 years, and median age of 63.50 years. The most prevalent preoperative PSA in patients with BCR was between 10-20 ng/ml (40.90%) and the most prevalent clinical stage was cT2 (59.10%). Regarding the Gleason score, the BCR patients had the most prevalent 6 (36.37%) score in the biopsy and score 7 (4 + 3) (36.37%) in the surgical specimen. All patients (100%) with BCR presented perineural invasion, with pT3 staging (81.81%) and pN0 (77.28%) being the most prevalent in patients with BCR. Patients with BCR presented a correlation (p<0.05) between the increase in the sum of pathological GS and the increase in pTN staging. Conclusion - All these variables were important in the determination of BCR in patients submitted to RP-LD, thus demonstrating the importance of this information in the analysis of the prognosis and in the follow-up of these patients.
Epidemiological studies have shown that in Western countries prostate cancer (PCa) is the most frequently diagnosed malignant neoplasm and the second leading cause of cancer-related death in males. Radical prostatectomy (RP) is the standard surgical treatment and among patients undergoing this treatment there is a survival benefit, especially in cases where the disease is localized1,2.
Biochemical recurrence (BCR) after surgical treatment of PCa is a possible event. Studies have shown that about 25% of men who underwent RP will have PCa BCR, and 34% of patients with BCR will develop metastatic disease3,4,5.
The BCR is directly associated with the presence of positive surgical margins, and the oncological prognosis is impaired in cases where the margins impairment is detected. According to Swindle et al. the positive surgical margin is the only factor that can be influenced by surgery in the oncological prognosis after performing the RP and the incidence ranges from 6 to 41%11,12,13.
Serum prostate-specific antigen (PSA) is the most sensitive indicator of BCR after definitive local therapy for PCa. All patients who develop clinical relapse, local or distant, will have detectable serum levels of PSA3. There are several definitions of relapse after RP. The most used and accepted method consists of two measures of PSA >0.2 ng/ml6,14.
Tumor pathological staging, Gleason score (GS), seminal vesicle invasion, lymphatic invasion and surgical margins were considered as factors to predict the subsequent risk of BCR after RP7,8,9,10. In this sense, our study evaluated the most prevalent clinical and pathological staging in patients with BCR, the compromised surgical margins and the correlation of the Gleason score of the biopsy and the surgical specimen.
Materials and Methods
Descriptors of the analyzed patients
We analyzed 100 patients diagnosed with adenocarcinoma of the prostate who underwent RP-LD between 2013 to 2017. After the selection of these patients, we collected information through electronic medical records and anatomopathological reports retrospectively. All patients enrolled in the study underwent transrectal prostate biopsy because of changes in PSA or rectal examination. The image of the prostate was obtained by transrectal ultrasound, which also guided the collection of the fragments for histopathological analysis by puncture, sextant using a 18-gauge needle. After determination of the Gleason biopsy and surgical indications for RP-LD, patients were surgically treated for curative purposes. The lymphadenectomy performed in the study was iliac-obturator. After surgery, the surgical specimens were analyzed by anatomopathological study to determine: pathological gleason; measurements of prostate length (cm); prostate volume; angiovascular/perineural invasions; invasions of the seminal vesicles; surgical margins (bladder and urethral); pathological staging pTNM. The criteria considered for BCR were all those patients submitted to LD-PR who presented two or more PSA measurements with values above 0.2 ng/ml in post-surgical follow-up.
Approval at the Research Ethics
The present study was approved by the Research Ethics Committee of the Base Institute of the Federal District, Brasília, CAAE: 93792918.8.0000.8153.
Statistical analysis
The descriptors collected retrospectively were grouped in Excel table for grouping and analysis of the variables and the variables analyzed were computed using SPSS 20.0. Variables such as clinical and pathological staging, surgical margins and the sum of the pathological Gleason were considered statistically significant for the correlation of the variables using the Pearson correlation (p <0.05).
After analysis of clinical and pathological characteristics (Table 1), it was found that 22% of the patients submitted to RP-LD presented BCR. Patients with BCR had a 59-76 age range, mean age of 66.27 years, and median age of 63.50 years. The most prevalent preoperative PSA (ng/ml) of patients without BCR were <10 ng/ml (52.26%) and in patients with BCR were between 10-20 ng/ml (40.90%). The most prevalent clinical staging of both non-BCR and BCR patients was cT2 with prevalence of (51.28%) and (59.10%) respectively.
Table 1. General data of the analyzed patients
When the values of the GS of the biopsy and the surgical specimen were added together, we showed that the patients with no BCR obtained the 7 (3 + 4) (38.46%) most prevalent sum in both the biopsy and the surgical specimen (61.53% ), but Gleason 6 (3 + 3) (36.37%) was more prevalent in the biopsy and Gleason 7 (4 + 3) (36.37%) in the surgical specimen.
The anatomic-pathological description of BCR patients showed that the majority (72.73%) were free of angiolymphatic neoplasia and 100% of them had perineural invasion; 72.73% had neoplasia-free right gallbladder; 59.10% had neoplasia-free left vesicle; 68.18% had positive extraprostatic extension; 86.36% had a neoplastic-free bladder surgical margin and 63.64% had a neoplastic-free urethral surgical margin. When analyzing the pathological staging of the surgical specimen, we found that pT3 staging (81.81%) and pN0 (77.28%) are the most prevalent in patients with BCR.
When analyzing the preoperative PSA and GS values of the biopsy in patients with BCR (Table 2), two (9.10%) patients presented preoperative PSA ≤ 10 ng/ml and GS 6 and eight (36.37%) patients presented preoperative PSA ≥10 ng/ml and GS≥7.
When analyzing the correlation of the multiple variables influenced in all the patients, it was evidenced that the patients with BCR had a correlation (p<0.05) with the increase of the sum of the pathological GS and with the increase of the pTN staging (Table 3). Thus demonstrating the importance of these variables in the prognosis of these patients analyzed.
In a cross-analysis of patients with BCR and their pathological stages (Graphic 1), 14 (63.64%) patients had staging (pT3N0) and 4 (18.19%) had staging (pT3N1), 3 (13.64%) had staging (pT2N0) and 1 (4.53%) had staging (pT2N0). These correlated variables did not reach a p<0.05 and, therefore, were not significant.
Discussion
Approximately 20-40% of men undergoing RP will present BCR within 10 years after treatment. It is suggested that there is a relationship between PSA doubling time and the biological behavior of adenocarcinoma of the prostate14. When analyzing 100 patients with prostatic adenocarcinoma who underwent RP, the prevalence of BCR in the study was 22%.
The value of preoperative PSA levels was considered an important predictor in the determination of pathological findings and the best clinical predictor in the determination of BCR after RP15. The combination of clinical PSA and GS biopsy descriptors identified the risk stratification for BCR, with patients with preoperative PSA ≤10 ng/ml and GS ≤6 presenting low risk for BCR and patients with preoperative PSA ≥10 ng/ml and GS ≥7 are at high risk for BCR and distant metastases15. Our study, when analyzing patients with BCR, showed that 14 (63.63%) patients had preoperative PSA ≥10 ng/ml and 14 (63.63%) patients had GS ≥ 7, so that 2 (9.10%) patients presented preoperative PSA ≤10 ng/ml and GS 6 and 8 (36.37%) had preoperative PSA ≥10 ng/ml and GS ≥7. Preoperative PSA prevalence of BCR patients were between 10-20 ng/ml (40.90%) (Table 1 and 2).
Several studies have considered GS as the most powerful predictor of BCR after RP, some studies have determined that the majority of men at risk for BCR after RP have Gleason disease 717,18. In the past, some studies have determined that the proportion of disease with GS pattern within 4/5 within PR specimens was predictive of both BCR and cancer-specific survival after RP19,20,21,22. In this respect, compelling evidence that the differentiation between Gleason 4 + 3 and 3 + 4 is a significant predictor of BCR after RP23. In this sense, studies have determined that a quantitative and more discriminative scoring system within the group of GS 7 patients may improve the ability to predict better and more appropriately which patients with Gleason 7 disease will present BCR17. Stratifying the GS of the biopsy in 3 + 4 and 4 + 3, it was verified that the patients with BCR obtained 6 (36.37%) more prevalent in the biopsy and 7 (4 + 3) (36.37%) in the part and that no patient with GS biopsy 7 (4 + 3) had preoperative PSA ≥10 ng/ml (Table 1 and 2). When correlating pathological GS and pTN staging, a significant correlation (p<0.05) between GS increase, increase in tumor invasion (pT) and lompa node involvement (pN) was observed (Table 3).
Prostate cancer may spread to the base of the gland along the ejaculatory ducts, penetrate the capsule through the perineural spaces, resulting in periprostatic growth, and may reach the seminal vesicles by direct capsule penetration24,25. Based on this, some studies have determiné that the independent predictors of BCR were biopsy GS, positive surgical margins and seminal vesicle invasion. The surgical approach was a significant predictor of BCR in the univariate analyzes, although its significance disappeared in the multivariate analysis26. In our analysis of BCR patients, perineural invasion was found in 100% of the cases, 27.27% in the right gallbladder and 40.90% in the left vesicle, 68.18% had extraprostatic extension, and 31.82% had urethral surgical margin (Table 1). The analysis of pathological staging of the surgical specimen showed that pT3 staging (81.81%) and pN0 (77.28%) were the most prevalent in patients with BCR.
Conclusion
PCa is one of the most prevalent neoplasms in the world and its treatment is still under study. PR remains one of the most common forms of treatment and some patients may develop BCR. In our study, perineural invasion was present in all cases that presented BCR and there was a significant correlation of the increase of pathological GS with the increase of pTN staging evidencing the importance of these descriptors in the evaluation of BCR in patients who performed PR.
Source of financing
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Conflict of interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Acknowledgments
We would like to thank the team of the Nucleus of Cytopathology and Anatomy-Pathology of the Institute of the Base Hospital of the Federal District (NUCAP-IHBDF) for the help and assistance during the elaboration of this work. Special thanks to the MASTER of Forensic Biosciences, Specialists in Human and Pathological Anatomy Dinaldo de Lima Leite and Hercules Marcelo Gomes for the support.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
