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Prostate carcinoma is a highly prevalent biologically and clinically diverse disease, generally associated with a consistent elevation of prostate-specific antigen levels. Castration-resistant prostate cancer represents a heterogeneous clinical setting that ranges from patients with an asymptomatic prostate-specific antigen elevation after hormone blockade failure and good performance status to patients with significant debilitating symptoms and rapidly progressive disease, leading to death. Nonmetastatic castration-resistant prostate cancer is a transient disease stage defined over specific criteria established within a sensitive time period. The majority of the patients with nonmetastatic castration-resistant prostate cancer will eventually develop metastatic lesions, associated with prostate cancer-specific morbidity and mortality. However, progression to metastatic disease is a heterogeneous process still not fully understood, with studies suggesting that younger age, high Gleason score (> 7), high prostate-specific antigen levels, reduced prostate-specific antigen doubling time (< 6 months), and a rapid alkaline phosphatase rise as potentially associated factors. Although the nonmetastatic castration-resistant prostate cancer treatment landscape has substantially evolved in recent years, the disease heterogeneity makes treatment decisions for this population challenging in the effort to achieve a balance between the risk of disease progression and the toxicity of new treatments in patients who often have associated comorbidities, yet are generally asymptomatic. The present article addresses the current main challenges in nonmetastatic castration-resistant prostate cancer management, including in diagnosis, owing to the development of new imaging modalities with a direct impact in disease detection, prognostic classification, as a result of the traditionally oversimplified definition of disease aggressiveness (mainly based on prostate-specific antigen doubling time), and patient selection for the most adequate treatment.

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Background: Seminoma accounts for 30-50% of testicular germ cell tumors (TGCT)-the most common solid malignancy in men aged 15-35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification's potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions. Methods: All consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed. Results: Seminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median followup time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b (P < 0.0001 and P = 0.023, respectively), known adverse biological features. Conclusions: In our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.