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2019 European Urology
doi: 10.1159/000480751
Clinical and pathologic staging of prostate cancer involves determination ofthe anatomic extent and burden of tumor based on the best available data. TheTNM system [primary tumor (T), regional lymph node (N), and métastasés(M)] is the most widely used system for prostate cancer staging. It stratifiespatients according to the method of tumor detection, separating nonpalpable‘incidental’ prostate cancers detected during transurethral resection for clinicallybenign prostatic hyperplasia and palpable cancers detected by digital rectalexamination. This staging system also recognizes nonpalpable cancerdetected by an elevated serum prostate-specific antigen level or an abnormaltransrectal ultrasound image (stage Tic). Current staging is limited by a significantlevel of clinical understaging (up to 59% in our experience) and overstaging(up to 5%) based on comparison with pathologic examination of resectedspecimens. Proposed improvements in staging include preoperative systematicbiopsies to assess tumor volume, the use of a volume-based prognosticindex, and a multiple prognostic index. Currently, staging of prostate cancerfalls short of meeting some of these goals, creating controversy and uncertaintyabout the comparative efficacy of various forms of therapy and expected outcomesfor patients. In this report, we evaluate the current aspects of clinicaland pathologic staging of prostate cancer with emphasis on the early stages inwhich there is the greatest chance of cure. Recent international agreement onthe pathologic staging of prostate cancer should allow valid comparisons ofsurgical treatment from different institutions.
Sakr, Wael A.; Grignon, David J.
2019 European Urology
doi: 10.1159/000480752
In spite of the slow progression rates common to most prostate cancers, it iswell recognized that a subset of patients will experience a more aggressivecourse with many losing their lives to this malignancy. As the number ofpatients diagnosed with prostate cancer continues to increase, there is a growingpressure to refine and supplement the three most important prognosticparameters for this disease (tumor pathologic stage, its histologic differentiation(Gleason score) and the level of prostate specific antigen). While thisreview emphasizes the value of these factors in stratifying patients into riskgroups, it also explores the prognostic significance of additional commonlyused and evolving non-traditional markers (DNA ploidy, proliferation, tumorangiogenesis, and the status of tumor suppressor genes).
Griffiths, K.; Morton, M.S.; Nicholson, R.I.
2019 European Urology
doi: 10.1159/000480753
Androgens play a major role in promoting the growth of the prostate gland.The DHT-androgen receptor complex, by association with the androgenresponse elements, specifically promotes this androgenic effect on the genome.Also recognized now, however, is that there is a close relationship between thisandrogen-mediated signalling pathway and those promoted by peptide growthfactors, the crosstalk between the pathways being pivotal to growth regulatorycontrol. This is discussed together with the perceived clinical potential of tyrosinekinase inhibitors for the treatment of prostate cancer, when the intracellularsignalling, induced by the growth stimulatory factors, can be repressed.
Schulman, Claude C.; Wildschutz, Thierry; Zlotta, Alexandre R.
2019 European Urology
doi: 10.1159/000480754
Since the advent of reversible androgen deprivation, its use for a short periodof time (usually 3 months) before radical prostatectomy has been advocated byan increasing number of urologists without clear and definitive proof of itsadvantage. Most authors have demonstrated downsizing of the prostate bysome 30-50%. Clinical downstaging was demonstrated in about 30% but thiscould not be confirmed at final pathological staging although downgradingwas noted in some 10% of the series analyzed. Reduction of positive marginsin patients receiving neoadjuvant treatment varies between 15% and 25%compared to control group. Several biases may however complicate the analysisof these results, the main cause of misinterpretation being the difficultyencountered by the pathologist to properly grade and score the tumor afterhormonal deprivation. Even if some early significant advantages can beobserved such as a decrease of positive margins and anecdotal complete disappearanceof tumor in some specimens, this may not necessarily alter the metastaticspread and the overall surivai rate. Only long follow-up in large prospectiverandomized studies evaluating biological (PSA) and clinical failures, timeto progression and survival will allow definitive conclusions on this still controversialapproach.
2019 European Urology
doi: 10.1159/000480755
The optimal treatment for many unresectable solid tumors involves the combineduse of chemotherapy and radiation. Retrospective and prospective randomizedtrials demonstrating a reduction in failure rates when neoadjuvantandrogen suppression is combined with radiotherapy suggest that this is alsolikely to be true for prostate cancer. The absence of overlapping toxicities, thehigh response rates to androgen suppression, and the ease with which the prostateis included in radiotherapy portals makes the prostate an ideal site forchemoradiation. Since radiation and hormonally mediated apoptosis appearto be induced by different mechanisms their interaction may well be synergistic.Volumetric changes induced by hormonal suppression facilitate radioactiveimplantation in the prostate in men with large glands. This neoadjuvantapproach also reduces the amount of normal tissue to be irradiated when usedprior to 3-dimensional conformal radiotherapy while allowing higher doses tothe tumor. It may be particularly important to use antiandrogens to block the‘intraprostatic flare’ that may result from the testosterone surge induced byluteinizing hormone-releasing hormone in patients undergoing neoadjuvant(short course) androgen suppression. Men who are at particularly ‘high risk’for biochemical failure when treated with radiotherapy alone should probablyreceive a ‘longer’ course of complete neoadjuvant and possibly adjuvant hormonalblockade, but the optimal duration and sequence of androgen suppressionremain to be defined.
2019 European Urology
doi: 10.1159/000480756
The early recurrence of prostate cancer originally staged as locally more thanT2 and nonmetastatic, cast doubts over the adequacy of the staging of thisform of the disease. Monotherapy with curative intent, either by radical prostatectomyor radiotherapy, results in around half of the patients failing within5 years. While improvements in staging of the disease are essential, the earlyresults of combined modality therapy, particularly the combination of neoadjuvanthormones and surgery, have been disappointing. Neo-adjuvant maximalandrogen blockade followed by radiotherapy does appear to offer survivalbenefit for patients with locally advanced disease, and other studies combiningradiotherapy adjuvant hormonal therapy and surgery with routine postoperativewith radiotherapy are eagerly awaited. Combination therapy might notgive the hoped-for additive effects of the two therapies, but almost certainlywill give an increased incidence of complications.
2019 European Urology
doi: 10.1159/000480757
Pelvic lymph node dissection is a routine staging procedure in localized prostatecancer. It provides prognostic information, it influences the design of thesubsequent therapeutic strategy and it provides information necessary to comparethe results of various therapeutic strategies. It is not considered a curativeprocedure. Thanks to improved diagnostic means, the unexpected finding ofpositive lymph nodes has decreased from 30% 15 years ago to below 10%.Hence, today the procedure is unnecessary in over 90% of the cases. Improvementsin staging by imaging techniques, including CT scan, MRI, ultrasound,and ileopelvic scintigraphy, have so far been unsuccessful because of low specificityand sensitivity. Using a combination of tumor grade and stage plusserum prostate-specific antigen (PSA) levels, a good indication of the likelihoodof positive pelvic nodes can be obtained. A review of the literature indicatesthat for clinically localized tumors, i.e. stages Tla to T2b, lymph nodedissection can be omitted provided serum PSA levels are < 10 ng/ml and thetumor is well to moderately well differentiated (Gleason grade <7). Usingthese cutoff values, approximately 25% of our patients can be saved a pelviclymph node dissection at the price of approximately 3% missed cases.
2019 European Urology
doi: 10.1159/000480758
Objective: To identify which patients with prostate cancer are at high risk forlocal or distant recurrence after radical prostatectomy. Methods: Review ofdata from several historical and contemporary series of patients undergoingradical prostatectomy. Results: Patients with high-grade disease (i.e., Gleasonscore ≥8), positive margins, and seminal vesicle invasion have relatively highrisks of biochemical and clinical failure if no adjuvant therapy is given. Use ofradiation therapy may improve local control rates for a subset of these patients(i.e., those with positive margins) but appears to have little impact on the laterdevelopment of metastatic disease or of prostate cancer death. Hormone therapymay delay the onset of failure for other patients with ‘high-risk’ disease butthere are few data to support its widespread use. Conclusions: Enhanced abilityto predict which patients with high-risk prostate cancer will fail locally afterradical prostatectomy is needed. Such patients should then be enrolled in arandomized study of postoperative adjuvant radiation therapy. Similarly,patients predicted to be at high risk for distant failure should be enrolled intrials evaluating conventional and ‘novel’ forms of hormonal therapy (i.e.,potency sparing regimens) to determine whether such therapy delays the timeto biochemical or clinical progression without compromising the patient’squality of life.
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